- Author:
- pmr2.import <nobody@models.cellml.org>
- Date:
- 2009-06-17 13:16:13+12:00
- Desc:
- committing version05 of clancy_rudy_2002
- Permanent Source URI:
- https://staging.physiomeproject.org/workspace/clancy_rudy_2002/rawfile/2676008998fea66125df99584a0a6d39af04fd3c/clancy_rudy_2002.cellml
<?xml version='1.0' encoding='utf-8'?>
<!-- FILE : clancy_model_II_2002.xml
CREATED : 20th August 2003
LAST MODIFIED : 21st April 2005
AUTHOR : Catherine Lloyd
The Bioengineering Institute
The University of Auckland
MODEL STATUS : This model conforms to the CellML 1.0 Specification released on
10th August 2001, and the CellML Metadata 1.0 Specification released on 16th
January, 2002.
DESCRIPTION : This file contains a CellML description of Clancy and Rudy's 2002 mathematical model of a Na channel mutation that causes both Brugada and long-QT syndrome phenotypes.
CHANGES:
21/04/2005 - PJV - Removed unnecessary type
--><model xmlns="http://www.cellml.org/cellml/1.0#" xmlns:cmeta="http://www.cellml.org/metadata/1.0#" xmlns:dc="http://purl.org/dc/elements/1.1/" xmlns:rdf="http://www.w3.org/1999/02/22-rdf-syntax-ns#" xmlns:bqs="http://www.cellml.org/bqs/1.0#" xmlns:cellml="http://www.cellml.org/cellml/1.0#" xmlns:dcterms="http://purl.org/dc/terms/" xmlns:vCard="http://www.w3.org/2001/vcard-rdf/3.0#" cmeta:id="clancy_rudy_2002" name="clancy_rudy_2002">
<documentation xmlns="http://cellml.org/tmp-documentation">
<article>
<articleinfo>
<title>A Single Mutation Underlies Brugada and LQT</title>
<author>
<firstname>Catherine</firstname>
<surname>Lloyd</surname>
<affiliation>
<shortaffil>Bioengineering Institute, University of Auckland</shortaffil>
</affiliation>
</author>
</articleinfo>
<section id="sec_status">
<title>Model Status</title>
<para>
This model can not be solved as it is unsuitably constrained.
</para>
<para>
ValidateCellML verifies this model as valid CellML but detects unit inconsistencies.
</para>
</section>
<sect1 id="sec_structure">
<title>Model Structure</title>
<para>
Long-QT and Brugada syndrome have both been linked with mutations in the <emphasis>SCN5A</emphasis> gene, which encodes the alpha subunit of the cardiac sodium channel. The specific mutation discussed here is a single mutation in the C terminus of the cardiac Na<superscript>+</superscript> channel, 1795insD. In LQT syndrome, the mutation causes a gain in Na<superscript>+</superscript> function, which leads to a persistent <emphasis>I<subscript>Na</subscript>
</emphasis>, which in turn causes a prolonged action potential duration that can facilitate the development of arrythmogenic early afterdepolarisations (EADs). These EADs are manifested on the body surface ECG as a longer QT interval. Conversely, the <emphasis>SCN5A</emphasis> mutation in Brugada syndrome reduces <emphasis>I<subscript>Na</subscript>
</emphasis>. This has the effect of supressing the action potential plateau in cells with prominent <emphasis>I<subscript>to</subscript>
</emphasis> (such as right ventricular epicardial cells), which is manifested as ST-segment elevation on the ECG.
</para>
<para>
The fact that a mutation in the same gene can have two apparently opposite affects on the phenotype illustrates how complex physiological interactions determine the functional consequences of gene expression. Within the myocardium, ion channel proteins are non-uniformly expressed, resulting in an intrinsic heterogeneity. In this 2002 study, Colleen Clancy and Yoram Rudy use a computational approach to demonstrate how heterogeneity in the myocardium allows seemingly paradoxical phenotypes associated with the 1795insD mutation to coexist. They develop Markov models of the wild type (<xref linkend="fig_cell_diagram1"/>) and 1795insD (<xref linkend="fig_cell_diagram2"/>) cardiac Na<superscript>+</superscript> channels. These are embedded within the <ulink url="${HTML_EXMPL_LR_II_MODEL}">Luo-Rudy dynamic model of a ventricular cell</ulink>. The particular version of the model which is used here has been updated with a slowly activating, delayed-rectifier potassium current (<emphasis>I<subscript>Ks</subscript>
</emphasis>), as described in <ulink url="${HTML_EXMPL_UPDATED_LR_II_MODEL}">Viswanathan <emphasis>et al.</emphasis>, 1999</ulink>, and the model also incorporates a transient outward potassium current (<emphasis>I<subscript>to</subscript>
</emphasis>), as described by <ulink url="${HTML_EXMPL_DUMAINE_MODEL}">Dumaine <emphasis>et al.</emphasis>, 1999</ulink>.
</para>
<para>
By incorporating the Markov models into a virtual cell, Clancy and Rudy were able to elucidate the mechanisms by which 1795insD differentially disrupts cellular electrophysiological behaviour. The results of their model simulations suggest that the interaction between the myocardial electrophysiological heterogeneity and the mutation-induced changes in <emphasis>I<subscript>Na</subscript>
</emphasis> provide the foundation for the development of both ECG ST-segment elevation (in Brugada syndrome) and QT interval prolongation (in Long-QT syndrome) in a rate-dependent manner. This study emphasises the complexity of genotype-phenotype relationships, and also the value of computational simulations in determining the link between the genetic mutations and functional abnormalities.
</para>
<para>
The complete original paper reference is cited below:
</para>
<para>
Na<superscript>+</superscript> Channel Mutation That Causes Both Brugada and Long-QT Syndrome Phenotypes: A Simulation Study of Mechanism, Colleen E. Clancy and Yoram Rudy, 2002,
<emphasis>Circulation</emphasis>
, 105, 1208-1213. <ulink url="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=11889015&dopt=Abstract">PubMed ID: 11889015</ulink>
</para>
<para>
The raw CellML description of the Clancy and Rudy 2002 models can be downloaded in various formats as described in <xref linkend="sec_download_this_model"/>.
</para>
<informalfigure float="0" id="fig_cell_diagram1">
<mediaobject>
<imageobject>
<objectinfo>
<title>cell diagram</title>
</objectinfo>
<imagedata fileref="clancy_2002a.png"/>
</imageobject>
</mediaobject>
<caption>A Markovian model for the wild-type cardiac Na<superscript>+</superscript> channel, embedded within an updated version of the Luo-Rudy dynamic model. C, indicates a closed channel state; IC, a closed-inactivation state; IF, a fast inactivation state; IM, an intermediate inactivation state, and O, an open state.</caption>
</informalfigure>
<informalfigure float="0" id="fig_cell_diagram2">
<mediaobject>
<imageobject>
<objectinfo>
<title>cell diagram2</title>
</objectinfo>
<imagedata fileref="clancy_2002b.png"/>
</imageobject>
</mediaobject>
<caption>A Markovian model for the mutant 1795insD cardiac Na<superscript>+</superscript> channel, embedded within an updated version of the Luo-Rudy dynamic model. U (upper) indicates background mode of gating; L (lower), represents a small population of bursting channels which fail to inactivate.</caption>
</informalfigure>
</sect1>
</article>
</documentation>
<!--
Below, we define some additional units for association with variables and
constants within the model. The identifiers are fairly self-explanatory.
-->
<units name="millisecond">
<unit units="second" prefix="milli"/>
</units>
<units name="per_millisecond">
<unit units="second" prefix="milli" exponent="-1"/>
</units>
<units name="millivolt">
<unit units="volt" prefix="milli"/>
</units>
<units name="per_millivolt">
<unit units="volt" prefix="milli" exponent="-1"/>
</units>
<units name="per_millivolt_millisecond">
<unit units="millivolt" exponent="-1"/>
<unit units="millisecond" exponent="-1"/>
</units>
<units name="milliS_per_microF">
<unit units="siemens" prefix="milli"/>
<unit units="farad" prefix="milli" exponent="-1"/>
</units>
<units name="milliS_per_cm2">
<unit units="siemens" prefix="milli"/>
<unit units="metre" prefix="centi" exponent="-2"/>
</units>
<units name="nanoS_per_cm2">
<unit units="siemens" prefix="nano"/>
<unit units="metre" prefix="centi" exponent="-2"/>
</units>
<units name="microF">
<unit units="farad" prefix="micro"/>
</units>
<units name="microA_per_microF">
<unit units="ampere" prefix="micro"/>
<unit units="farad" prefix="micro" exponent="-1"/>
</units>
<units name="millimolar_per_millisecond">
<unit units="mole" prefix="milli"/>
<unit units="litre" exponent="-1"/>
<unit units="millisecond" exponent="-1"/>
</units>
<units name="millimolar">
<unit units="mole" prefix="milli"/>
<unit units="litre" exponent="-1"/>
</units>
<units name="micromolar">
<unit units="mole" prefix="micro"/>
<unit units="litre" exponent="-1"/>
</units>
<units name="joule_per_kilomole_kelvin">
<unit units="joule"/>
<unit units="mole" prefix="kilo" exponent="-1"/>
<unit units="kelvin" exponent="-1"/>
</units>
<units name="coulomb_per_mole">
<unit units="coulomb"/>
<unit units="mole" exponent="-1"/>
</units>
<units name="cm_per_second">
<unit units="metre" prefix="centi"/>
<unit units="second" exponent="-1"/>
</units>
<units name="cm2">
<unit units="metre" prefix="centi" exponent="2"/>
</units>
<units name="mm2">
<unit units="metre" prefix="milli" exponent="2"/>
</units>
<units name="micro_litre">
<unit units="litre" prefix="micro"/>
</units>
<!--
The "environment" component is used to declare variables that are used by
all or most of the other components, in this case just "time".
-->
<component name="environment">
<variable units="millisecond" public_interface="out" name="time"/>
</component>
<component name="membrane">
<variable units="millivolt" public_interface="out" name="V" initial_value="-84.624"/>
<variable units="joule_per_kilomole_kelvin" public_interface="out" name="R" initial_value="8314.0"/>
<variable units="kelvin" public_interface="out" name="T" initial_value="310.0"/>
<variable units="coulomb_per_mole" public_interface="out" name="F" initial_value="96500.0"/>
<variable units="microF" name="Cm" initial_value="1.0"/>
<variable units="microA_per_microF" name="I_st" initial_value="-100.0"/>
<variable units="millisecond" public_interface="in" name="time"/>
<variable units="microA_per_microF" public_interface="in" name="i_Na"/>
<variable units="microA_per_microF" public_interface="in" name="i_Ca_L"/>
<variable units="microA_per_microF" public_interface="in" name="i_Ca_T"/>
<variable units="microA_per_microF" public_interface="in" name="i_Kr"/>
<variable units="microA_per_microF" public_interface="in" name="i_Ks"/>
<variable units="microA_per_microF" public_interface="in" name="i_NaCa"/>
<variable units="microA_per_microF" public_interface="in" name="i_K1"/>
<variable units="microA_per_microF" public_interface="in" name="i_Kp"/>
<variable units="microA_per_microF" public_interface="in" name="i_p_Ca"/>
<variable units="microA_per_microF" public_interface="in" name="i_Na_b"/>
<variable units="microA_per_microF" public_interface="in" name="i_Ca_b"/>
<variable units="microA_per_microF" public_interface="in" name="i_NaK"/>
<variable units="microA_per_microF" public_interface="in" name="i_ns_Ca"/>
<variable units="microA_per_microF" public_interface="in" name="i_K_ATP"/>
<variable units="microA_per_microF" public_interface="in" name="i_to"/>
<math xmlns="http://www.w3.org/1998/Math/MathML">
<apply id="membrane_voltage_diff_eq">
<eq/>
<apply>
<diff/>
<bvar>
<ci> time </ci>
</bvar>
<ci> V </ci>
</apply>
<apply>
<times/>
<apply>
<minus/>
<apply>
<divide/>
<cn cellml:units="dimensionless"> 1.0 </cn>
<ci> Cm </ci>
</apply>
</apply>
<apply>
<plus/>
<ci> i_Na </ci>
<ci> i_Ca_L </ci>
<ci> i_Ca_T </ci>
<ci> i_Kr </ci>
<ci> i_Ks </ci>
<ci> i_K1 </ci>
<ci> i_K_ATP </ci>
<ci> i_Kp </ci>
<ci> i_NaCa </ci>
<ci> i_p_Ca </ci>
<ci> i_Na_b </ci>
<ci> i_Ca_b </ci>
<ci> i_NaK </ci>
<ci> i_ns_Ca </ci>
<ci> i_to </ci>
<ci> I_st </ci>
</apply>
</apply>
</apply>
</math>
</component>
<component name="transient_outward_potassium_current">
<variable units="microA_per_microF" public_interface="out" name="i_to"/>
<variable units="milliS_per_microF" name="g_to" initial_value="1.1"/>
<variable units="dimensionless" name="R_to"/>
<variable units="millisecond" public_interface="in" private_interface="out" name="time"/>
<variable units="millivolt" public_interface="in" private_interface="out" name="V"/>
<variable units="millivolt" public_interface="in" name="E_K"/>
<variable units="dimensionless" private_interface="in" name="z"/>
<variable units="dimensionless" private_interface="in" name="y"/>
<math xmlns="http://www.w3.org/1998/Math/MathML">
<apply id="i_to_calculation">
<eq/>
<ci> i_to </ci>
<apply>
<times/>
<ci> g_to </ci>
<apply>
<power/>
<ci> z </ci>
<cn cellml:units="dimensionless"> 3.0 </cn>
</apply>
<ci> y </ci>
<ci> R_to </ci>
<apply>
<minus/>
<ci> V </ci>
<ci> E_K </ci>
</apply>
</apply>
</apply>
<apply id="R_to_calculation">
<eq/>
<ci> R_to </ci>
<apply>
<exp/>
<apply>
<divide/>
<ci> V </ci>
<cn cellml:units="millivolt"> 100.0 </cn>
</apply>
</apply>
</apply>
</math>
</component>
<component name="transient_outward_potassium_current_z_gate">
<variable units="dimensionless" public_interface="out" name="z"/>
<variable units="per_millisecond" name="alpha_z"/>
<variable units="per_millisecond" name="beta_z"/>
<variable units="millivolt" public_interface="in" name="V"/>
<variable units="millisecond" public_interface="in" name="time"/>
<math xmlns="http://www.w3.org/1998/Math/MathML">
<apply id="dz_dt">
<eq/>
<apply>
<diff/>
<bvar>
<ci> time </ci>
</bvar>
<ci> z </ci>
</apply>
<apply>
<minus/>
<apply>
<times/>
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<apply>
<minus/>
<cn cellml:units="dimensionless"> 1.0 </cn>
<ci> z </ci>
</apply>
</apply>
<apply>
<times/>
<ci> beta_z </ci>
<ci> z </ci>
</apply>
</apply>
</apply>
<apply id="alpha_z_calculation">
<eq/>
<ci> alpha_z </ci>
<apply>
<divide/>
<apply>
<times/>
<cn cellml:units="per_millisecond"> 10.0 </cn>
<apply>
<exp/>
<apply>
<divide/>
<apply>
<minus/>
<ci> V </ci>
<cn cellml:units="millivolt"> 40.0 </cn>
</apply>
<cn cellml:units="millivolt"> 25.0 </cn>
</apply>
</apply>
</apply>
<apply>
<plus/>
<cn cellml:units="dimensionless"> 1.0 </cn>
<apply>
<exp/>
<apply>
<divide/>
<apply>
<minus/>
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</apply>
<cn cellml:units="millivolt"> 25.0 </cn>
</apply>
</apply>
</apply>
</apply>
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<apply id="beta_z_calculation">
<eq/>
<ci> beta_z </ci>
<apply>
<divide/>
<apply>
<times/>
<cn cellml:units="per_millisecond"> 10.0 </cn>
<apply>
<exp/>
<apply>
<minus/>
<apply>
<divide/>
<apply>
<plus/>
<ci> V </ci>
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</apply>
<cn cellml:units="millivolt"> 25.0 </cn>
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<apply>
<exp/>
<apply>
<minus/>
<apply>
<divide/>
<apply>
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<ci> V </ci>
<cn cellml:units="millivolt"> 90.0 </cn>
</apply>
<cn cellml:units="millivolt"> 25.0 </cn>
</apply>
</apply>
</apply>
</apply>
</apply>
</apply>
</math>
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<component name="transient_outward_potassium_current_y_gate">
<variable units="dimensionless" public_interface="out" name="y"/>
<variable units="per_millisecond" name="alpha_y"/>
<variable units="per_millisecond" name="beta_y"/>
<variable units="millivolt" public_interface="in" name="V"/>
<variable units="millisecond" public_interface="in" name="time"/>
<math xmlns="http://www.w3.org/1998/Math/MathML">
<apply id="dy_dt">
<eq/>
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<ci> time </ci>
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<apply>
<times/>
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<apply>
<minus/>
<cn cellml:units="dimensionless"> 1.0 </cn>
<ci> y </ci>
</apply>
</apply>
<apply>
<times/>
<ci> beta_y </ci>
<ci> y </ci>
</apply>
</apply>
</apply>
<apply id="alpha_y_calculation">
<eq/>
<ci> alpha_y </ci>
<apply>
<divide/>
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<apply>
<plus/>
<cn cellml:units="dimensionless"> 1.0 </cn>
<apply>
<exp/>
<apply>
<divide/>
<apply>
<plus/>
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<cn cellml:units="millivolt"> 60.0 </cn>
</apply>
<cn cellml:units="millivolt"> 5.0 </cn>
</apply>
</apply>
</apply>
</apply>
</apply>
<apply id="beta_y_calculation">
<eq/>
<ci> beta_y </ci>
<apply>
<divide/>
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<times/>
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<apply>
<exp/>
<apply>
<divide/>
<apply>
<plus/>
<ci> V </ci>
<cn cellml:units="millivolt"> 25.0 </cn>
</apply>
<cn cellml:units="millivolt"> 5.0 </cn>
</apply>
</apply>
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<apply>
<plus/>
<cn cellml:units="dimensionless"> 1.0 </cn>
<apply>
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<divide/>
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<ci> V </ci>
<cn cellml:units="millivolt"> 25.0 </cn>
</apply>
<cn cellml:units="millivolt"> 5.0 </cn>
</apply>
</apply>
</apply>
</apply>
</apply>
</math>
</component>
<component name="fast_sodium_current">
<variable units="microA_per_microF" public_interface="out" name="i_Na"/>
<variable units="millivolt" public_interface="out" name="E_Na"/>
<variable units="milliS_per_microF" name="g_Na" initial_value="23.5"/>
<variable units="millisecond" public_interface="in" private_interface="out" name="time"/>
<variable units="millivolt" public_interface="in" private_interface="out" name="V"/>
<variable units="joule_per_kilomole_kelvin" public_interface="in" name="R"/>
<variable units="kelvin" public_interface="in" name="T"/>
<variable units="coulomb_per_mole" public_interface="in" name="F"/>
<variable units="millimolar" public_interface="in" name="Nao"/>
<variable units="millimolar" public_interface="in" name="Nai"/>
<variable units="dimensionless" private_interface="in" name="P_O_Na"/>
<math xmlns="http://www.w3.org/1998/Math/MathML">
<apply id="i_Na_calculation">
<eq/>
<ci> i_Na </ci>
<apply>
<times/>
<ci> g_Na </ci>
<ci> P_O_Na </ci>
<apply>
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<ci> E_Na </ci>
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<apply>
<ln/>
<apply>
<divide/>
<ci> Nao </ci>
<ci> Nai </ci>
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</apply>
</apply>
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</component>
<component name="Na_channel_states" cmeta:id="Na_channel_states">
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<variable units="dimensionless" name="P_LO"/>
<variable units="dimensionless" name="P_UO"/>
<variable units="dimensionless" name="P_LC1"/>
<variable units="dimensionless" name="P_LC2"/>
<variable units="dimensionless" name="P_LC3"/>
<variable units="dimensionless" name="P_UIF"/>
<variable units="dimensionless" name="P_UC1"/>
<variable units="dimensionless" name="P_UC2"/>
<variable units="dimensionless" name="P_UC3"/>
<variable units="dimensionless" name="P_UIC3"/>
<variable units="dimensionless" name="P_UIC2"/>
<variable units="dimensionless" name="P_UIM1"/>
<variable units="dimensionless" name="P_UIM2"/>
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<variable units="per_millisecond" name="beta_11"/>
<variable units="per_millisecond" name="alpha_12"/>
<variable units="per_millisecond" name="beta_12"/>
<variable units="per_millisecond" name="alpha_13"/>
<variable units="per_millisecond" name="beta_13"/>
<variable units="per_millisecond" name="alpha_2"/>
<variable units="per_millisecond" name="beta_2"/>
<variable units="per_millisecond" name="alpha_3"/>
<variable units="per_millisecond" name="beta_3"/>
<variable units="per_millisecond" name="alpha_4"/>
<variable units="per_millisecond" name="beta_4"/>
<variable units="per_millisecond" name="alpha_5"/>
<variable units="per_millisecond" name="beta_5"/>
<variable units="millisecond" public_interface="in" name="time"/>
<variable units="millivolt" public_interface="in" name="V"/>
<math xmlns="http://www.w3.org/1998/Math/MathML">
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<ci> P_UO </ci>
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<ci> P_LC3 </ci>
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<apply>
<minus/>
<apply>
<times/>
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<cn cellml:units="per_millisecond" type="e-notation"> 9.5<sep/>-4 </cn>
<ci> alpha_11 </ci>
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<ci> P_LC3 </ci>
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<apply>
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<cn cellml:units="per_millisecond" type="e-notation"> 1<sep/>-7 </cn>
<ci> P_UC3 </ci>
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<apply>
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<ci> beta_11 </ci>
<ci> P_LC2 </ci>
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<ci> P_LC2 </ci>
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<ci> beta_11 </ci>
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<ci> alpha_12 </ci>
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<ci> P_LC3 </ci>
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<ci> P_LC1 </ci>
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<ci> P_UC2 </ci>
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<eq/>
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<ci> P_LC1 </ci>
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<minus/>
<apply>
<times/>
<apply>
<plus/>
<ci> beta_12 </ci>
<ci> alpha_13 </ci>
<cn cellml:units="per_millisecond" type="e-notation"> 9.5<sep/>-4 </cn>
</apply>
<ci> P_LC1 </ci>
</apply>
</apply>
<apply>
<times/>
<ci> alpha_12 </ci>
<ci> P_LC2 </ci>
</apply>
<apply>
<times/>
<ci> beta_13 </ci>
<ci> P_LO </ci>
</apply>
<apply>
<times/>
<cn cellml:units="per_millisecond" type="e-notation"> 1<sep/>-7 </cn>
<ci> P_UC1 </ci>
</apply>
</apply>
</apply>
<apply id="P_LO_diff_eq">
<eq/>
<apply>
<diff/>
<bvar>
<ci> time </ci>
</bvar>
<ci> P_LO </ci>
</apply>
<apply>
<plus/>
<apply>
<minus/>
<apply>
<times/>
<apply>
<plus/>
<cn cellml:units="per_millisecond" type="e-notation"> 9.5<sep/>-4 </cn>
<ci> beta_13 </ci>
</apply>
<ci> P_LO </ci>
</apply>
</apply>
<apply>
<times/>
<cn cellml:units="per_millisecond" type="e-notation"> 1<sep/>-7 </cn>
<ci> P_UO </ci>
</apply>
<apply>
<times/>
<ci> alpha_13 </ci>
<ci> P_LC1 </ci>
</apply>
</apply>
</apply>
<apply id="P_UIF_diff_eq">
<eq/>
<apply>
<diff/>
<bvar>
<ci> time </ci>
</bvar>
<ci> P_UIF </ci>
</apply>
<apply>
<plus/>
<apply>
<minus/>
<apply>
<times/>
<apply>
<plus/>
<ci> beta_2 </ci>
<ci> alpha_3 </ci>
<ci> alpha_4 </ci>
<ci> beta_12 </ci>
</apply>
<ci> P_UIF </ci>
</apply>
</apply>
<apply>
<times/>
<ci> beta_3 </ci>
<ci> P_UC1 </ci>
</apply>
<apply>
<times/>
<ci> beta_4 </ci>
<ci> P_UIM1 </ci>
</apply>
<apply>
<times/>
<ci> alpha_2 </ci>
<ci> P_UO </ci>
</apply>
<apply>
<times/>
<ci> alpha_12 </ci>
<ci> P_UIC2 </ci>
</apply>
</apply>
</apply>
<apply id="P_UIC3_diff_eq">
<eq/>
<apply>
<diff/>
<bvar>
<ci> time </ci>
</bvar>
<ci> P_UIC3 </ci>
</apply>
<apply>
<plus/>
<apply>
<minus/>
<apply>
<times/>
<apply>
<plus/>
<ci> alpha_3 </ci>
<ci> alpha_11 </ci>
</apply>
<ci> P_UIC3 </ci>
</apply>
</apply>
<apply>
<times/>
<ci> beta_3 </ci>
<ci> P_UC3 </ci>
</apply>
<apply>
<times/>
<ci> beta_11 </ci>
<ci> P_UIC2 </ci>
</apply>
</apply>
</apply>
<apply id="P_UIC2_diff_eq">
<eq/>
<apply>
<diff/>
<bvar>
<ci> time </ci>
</bvar>
<ci> P_UIC2 </ci>
</apply>
<apply>
<plus/>
<apply>
<minus/>
<apply>
<times/>
<apply>
<plus/>
<ci> alpha_3 </ci>
<ci> alpha_12 </ci>
<ci> beta_11 </ci>
</apply>
<ci> P_UIC2 </ci>
</apply>
</apply>
<apply>
<times/>
<ci> beta_3 </ci>
<ci> P_UC2 </ci>
</apply>
<apply>
<times/>
<ci> beta_12 </ci>
<ci> P_UIF </ci>
</apply>
<apply>
<times/>
<ci> alpha_11 </ci>
<ci> P_UIC3 </ci>
</apply>
</apply>
</apply>
<apply id="P_UIM1_diff_eq">
<eq/>
<apply>
<diff/>
<bvar>
<ci> time </ci>
</bvar>
<ci> P_UIM1 </ci>
</apply>
<apply>
<plus/>
<apply>
<minus/>
<apply>
<times/>
<apply>
<plus/>
<ci> alpha_5 </ci>
<ci> beta_4 </ci>
</apply>
<ci> P_UIM1 </ci>
</apply>
</apply>
<apply>
<times/>
<ci> beta_5 </ci>
<ci> P_UIM2 </ci>
</apply>
<apply>
<times/>
<ci> alpha_4 </ci>
<ci> P_UIF </ci>
</apply>
</apply>
</apply>
<apply id="P_UIM2_diff_eq">
<eq/>
<apply>
<diff/>
<bvar>
<ci> time </ci>
</bvar>
<ci> P_UIM2 </ci>
</apply>
<apply>
<minus/>
<apply>
<times/>
<ci> alpha_5 </ci>
<ci> P_UIM1 </ci>
</apply>
<apply>
<times/>
<ci> beta_5 </ci>
<ci> P_UIM2 </ci>
</apply>
</apply>
</apply>
<apply id="P_UC3_diff_eq">
<eq/>
<apply>
<diff/>
<bvar>
<ci> time </ci>
</bvar>
<ci> P_UC3 </ci>
</apply>
<apply>
<plus/>
<apply>
<minus/>
<apply>
<times/>
<apply>
<plus/>
<ci> beta_3 </ci>
<ci> alpha_11 </ci>
<cn cellml:units="per_millisecond" type="e-notation"> 1<sep/>-7 </cn>
</apply>
<ci> P_UC3 </ci>
</apply>
</apply>
<apply>
<times/>
<ci> alpha_3 </ci>
<ci> P_UIC3 </ci>
</apply>
<apply>
<times/>
<ci> beta_11 </ci>
<ci> P_UC2 </ci>
</apply>
<apply>
<times/>
<cn cellml:units="per_millisecond" type="e-notation"> 9.5<sep/>-4 </cn>
<ci> P_LC3 </ci>
</apply>
</apply>
</apply>
<apply id="P_UC2_diff_eq">
<eq/>
<apply>
<diff/>
<bvar>
<ci> time </ci>
</bvar>
<ci> P_UC2 </ci>
</apply>
<apply>
<plus/>
<apply>
<minus/>
<apply>
<times/>
<apply>
<plus/>
<ci> beta_11 </ci>
<ci> beta_3 </ci>
<ci> alpha_12 </ci>
<cn cellml:units="per_millisecond" type="e-notation"> 1<sep/>-7 </cn>
</apply>
<ci> P_UC2 </ci>
</apply>
</apply>
<apply>
<times/>
<ci> alpha_11 </ci>
<ci> P_UC3 </ci>
</apply>
<apply>
<times/>
<ci> beta_12 </ci>
<ci> P_UC1 </ci>
</apply>
<apply>
<times/>
<ci> alpha_3 </ci>
<ci> P_UIC2 </ci>
</apply>
<apply>
<times/>
<cn cellml:units="per_millisecond" type="e-notation"> 9.5<sep/>-4 </cn>
<ci> P_LC2 </ci>
</apply>
</apply>
</apply>
<apply id="P_UC1_diff_eq">
<eq/>
<apply>
<diff/>
<bvar>
<ci> time </ci>
</bvar>
<ci> P_UC1 </ci>
</apply>
<apply>
<plus/>
<apply>
<minus/>
<apply>
<times/>
<apply>
<plus/>
<ci> beta_12 </ci>
<ci> alpha_13 </ci>
<ci> beta_3 </ci>
<cn cellml:units="per_millisecond" type="e-notation"> 1<sep/>-7 </cn>
</apply>
<ci> P_UC1 </ci>
</apply>
</apply>
<apply>
<times/>
<ci> alpha_12 </ci>
<ci> P_UC2 </ci>
</apply>
<apply>
<times/>
<ci> beta_13 </ci>
<ci> P_UO </ci>
</apply>
<apply>
<times/>
<ci> alpha_3 </ci>
<ci> P_UIF </ci>
</apply>
<apply>
<times/>
<cn cellml:units="per_millisecond" type="e-notation"> 9.5<sep/>-4 </cn>
<ci> P_LC1 </ci>
</apply>
</apply>
</apply>
<apply id="P_UO_diff_eq">
<eq/>
<apply>
<diff/>
<bvar>
<ci> time </ci>
</bvar>
<ci> P_UO </ci>
</apply>
<apply>
<plus/>
<apply>
<minus/>
<apply>
<times/>
<apply>
<plus/>
<ci> alpha_2 </ci>
<ci> beta_13 </ci>
<cn cellml:units="per_millisecond" type="e-notation"> 1<sep/>-7 </cn>
</apply>
<ci> P_UO </ci>
</apply>
</apply>
<apply>
<times/>
<ci> beta_2 </ci>
<ci> P_UIF </ci>
</apply>
<apply>
<times/>
<ci> alpha_13 </ci>
<ci> P_UC1 </ci>
</apply>
<apply>
<times/>
<cn cellml:units="per_millisecond" type="e-notation"> 9.5<sep/>-4 </cn>
<ci> P_LO </ci>
</apply>
</apply>
</apply>
<apply id="alpha_11_calculation">
<eq/>
<ci> alpha_11 </ci>
<apply>
<divide/>
<cn cellml:units="per_millisecond"> 3.802 </cn>
<apply>
<plus/>
<apply>
<times/>
<cn cellml:units="dimensionless"> 0.1027 </cn>
<apply>
<exp/>
<apply>
<divide/>
<apply>
<minus/>
<ci> V </ci>
</apply>
<cn cellml:units="millivolt"> 17.0 </cn>
</apply>
</apply>
</apply>
<apply>
<times/>
<cn cellml:units="dimensionless"> 0.20 </cn>
<apply>
<exp/>
<apply>
<divide/>
<apply>
<minus/>
<ci> V </ci>
</apply>
<cn cellml:units="millivolt"> 150.0 </cn>
</apply>
</apply>
</apply>
</apply>
</apply>
</apply>
<apply id="alpha_12_calculation">
<eq/>
<ci> alpha_12 </ci>
<apply>
<divide/>
<cn cellml:units="per_millisecond"> 3.802 </cn>
<apply>
<plus/>
<apply>
<times/>
<cn cellml:units="dimensionless"> 0.1027 </cn>
<apply>
<exp/>
<apply>
<divide/>
<apply>
<minus/>
<ci> V </ci>
</apply>
<cn cellml:units="millivolt"> 15.0 </cn>
</apply>
</apply>
</apply>
<apply>
<times/>
<cn cellml:units="dimensionless"> 0.23 </cn>
<apply>
<exp/>
<apply>
<divide/>
<apply>
<minus/>
<ci> V </ci>
</apply>
<cn cellml:units="millivolt"> 150.0 </cn>
</apply>
</apply>
</apply>
</apply>
</apply>
</apply>
<apply id="alpha_13_calculation">
<eq/>
<ci> alpha_13 </ci>
<apply>
<divide/>
<cn cellml:units="per_millisecond"> 3.802 </cn>
<apply>
<plus/>
<apply>
<times/>
<cn cellml:units="dimensionless"> 0.1027 </cn>
<apply>
<exp/>
<apply>
<divide/>
<apply>
<minus/>
<ci> V </ci>
</apply>
<cn cellml:units="millivolt"> 12.0 </cn>
</apply>
</apply>
</apply>
<apply>
<times/>
<cn cellml:units="dimensionless"> 0.25 </cn>
<apply>
<exp/>
<apply>
<divide/>
<apply>
<minus/>
<ci> V </ci>
</apply>
<cn cellml:units="millivolt"> 150.0 </cn>
</apply>
</apply>
</apply>
</apply>
</apply>
</apply>
<apply id="beta_11_calculation">
<eq/>
<ci> beta_11 </ci>
<apply>
<times/>
<cn cellml:units="per_millisecond"> 0.1917 </cn>
<apply>
<exp/>
<apply>
<divide/>
<apply>
<minus/>
<ci> V </ci>
</apply>
<cn cellml:units="millivolt"> 20.3 </cn>
</apply>
</apply>
</apply>
</apply>
<apply id="beta_12_calculation">
<eq/>
<ci> beta_12 </ci>
<apply>
<times/>
<cn cellml:units="per_millisecond"> 0.20 </cn>
<apply>
<exp/>
<apply>
<divide/>
<apply>
<minus/>
<apply>
<minus/>
<ci> V </ci>
<cn cellml:units="millivolt"> 5.0 </cn>
</apply>
</apply>
<cn cellml:units="millivolt"> 20.3 </cn>
</apply>
</apply>
</apply>
</apply>
<apply id="beta_13_calculation">
<eq/>
<ci> beta_13 </ci>
<apply>
<times/>
<cn cellml:units="per_millisecond"> 0.22 </cn>
<apply>
<exp/>
<apply>
<divide/>
<apply>
<minus/>
<apply>
<minus/>
<ci> V </ci>
<cn cellml:units="millivolt"> 10.0 </cn>
</apply>
</apply>
<cn cellml:units="millivolt"> 20.3 </cn>
</apply>
</apply>
</apply>
</apply>
<apply id="alpha_2_calculation">
<eq/>
<ci> alpha_2 </ci>
<apply>
<times/>
<cn cellml:units="per_millisecond"> 9.178 </cn>
<apply>
<exp/>
<apply>
<divide/>
<ci> V </ci>
<cn cellml:units="millivolt"> 29.68 </cn>
</apply>
</apply>
</apply>
</apply>
<apply id="beta_2_calculation">
<eq/>
<ci> beta_2 </ci>
<apply>
<divide/>
<apply>
<times/>
<ci> alpha_13 </ci>
<ci> alpha_2 </ci>
<ci> alpha_3 </ci>
</apply>
<apply>
<times/>
<ci> beta_13 </ci>
<ci> beta_3 </ci>
</apply>
</apply>
</apply>
<apply id="alpha_3_calculation">
<eq/>
<ci> alpha_3 </ci>
<apply>
<times/>
<cn cellml:units="per_millisecond" type="e-notation"> 3.7933<sep/>-7 </cn>
<apply>
<exp/>
<apply>
<divide/>
<apply>
<minus/>
<ci> V </ci>
</apply>
<cn cellml:units="millivolt"> 7.7 </cn>
</apply>
</apply>
</apply>
</apply>
<apply id="alpha_4_calculation">
<eq/>
<ci> alpha_4 </ci>
<apply>
<divide/>
<ci> alpha_2 </ci>
<cn cellml:units="dimensionless"> 100.0 </cn>
</apply>
</apply>
<apply id="beta_4_calculation">
<eq/>
<ci> beta_4 </ci>
<ci> alpha_3 </ci>
</apply>
<apply id="alpha_5_calculation">
<eq/>
<ci> alpha_5 </ci>
<apply>
<divide/>
<ci> alpha_2 </ci>
<cn cellml:units="dimensionless" type="e-notation"> 3.5<sep/>4 </cn>
</apply>
</apply>
<apply id="beta_5_calculation">
<eq/>
<ci> beta_5 </ci>
<apply>
<divide/>
<ci> alpha_3 </ci>
<cn cellml:units="dimensionless"> 20 </cn>
</apply>
</apply>
</math>
</component>
<component name="L_type_Ca_channel">
<variable units="microA_per_microF" public_interface="out" name="i_Ca_L"/>
<variable units="microA_per_microF" public_interface="out" name="i_CaCa"/>
<variable units="microA_per_microF" public_interface="out" name="i_CaK"/>
<variable units="microA_per_microF" public_interface="out" name="i_CaNa"/>
<variable units="dimensionless" public_interface="out" name="gamma_Nai" initial_value="0.75"/>
<variable units="dimensionless" public_interface="out" name="gamma_Nao" initial_value="0.75"/>
<variable units="dimensionless" public_interface="out" name="gamma_Ki" initial_value="0.75"/>
<variable units="dimensionless" public_interface="out" name="gamma_Ko" initial_value="0.75"/>
<variable units="microA_per_microF" name="I_CaCa"/>
<variable units="microA_per_microF" name="I_CaK"/>
<variable units="microA_per_microF" name="I_CaNa"/>
<variable units="cm_per_second" name="P_Ca" initial_value="0.00054"/>
<variable units="cm_per_second" name="P_Na" initial_value="0.000000675"/>
<variable units="cm_per_second" name="P_K" initial_value="0.000000193"/>
<variable units="dimensionless" name="gamma_Cai" initial_value="1.0"/>
<variable units="dimensionless" name="gamma_Cao" initial_value="0.34"/>
<variable units="millisecond" public_interface="in" private_interface="out" name="time"/>
<variable units="millivolt" public_interface="in" private_interface="out" name="V"/>
<variable units="micromolar" public_interface="in" private_interface="out" name="Cai"/>
<variable units="joule_per_kilomole_kelvin" public_interface="in" name="R"/>
<variable units="kelvin" public_interface="in" name="T"/>
<variable units="coulomb_per_mole" public_interface="in" name="F"/>
<variable units="millimolar" public_interface="in" name="Cao"/>
<variable units="millimolar" public_interface="in" name="Nao"/>
<variable units="millimolar" public_interface="in" name="Ko"/>
<variable units="millimolar" public_interface="in" name="Nai"/>
<variable units="millimolar" public_interface="in" name="Ki"/>
<variable units="dimensionless" private_interface="in" name="d"/>
<variable units="dimensionless" private_interface="in" name="f"/>
<variable units="dimensionless" private_interface="in" name="f_Ca"/>
<math xmlns="http://www.w3.org/1998/Math/MathML">
<apply id="i_CaCa_calculation">
<eq/>
<ci> i_CaCa </ci>
<apply>
<times/>
<ci> d </ci>
<ci> f </ci>
<ci> f_Ca </ci>
<ci> I_CaCa </ci>
</apply>
</apply>
<apply id="i_CaNa_calculation">
<eq/>
<ci> i_CaNa </ci>
<apply>
<times/>
<ci> d </ci>
<ci> f </ci>
<ci> f_Ca </ci>
<ci> I_CaNa </ci>
</apply>
</apply>
<apply id="i_CaK_calculation">
<eq/>
<ci> i_CaK </ci>
<apply>
<times/>
<ci> d </ci>
<ci> f </ci>
<ci> f_Ca </ci>
<ci> I_CaK </ci>
</apply>
</apply>
<apply id="I_CaCa_calculation">
<eq/>
<ci> I_CaCa </ci>
<apply>
<times/>
<ci> P_Ca </ci>
<apply>
<power/>
<cn cellml:units="dimensionless"> 2.0 </cn>
<cn cellml:units="dimensionless"> 2.0 </cn>
</apply>
<apply>
<divide/>
<apply>
<times/>
<ci> V </ci>
<apply>
<power/>
<ci> F </ci>
<cn cellml:units="dimensionless"> 2.0 </cn>
</apply>
</apply>
<apply>
<times/>
<ci> R </ci>
<ci> T </ci>
</apply>
</apply>
<apply>
<divide/>
<apply>
<minus/>
<apply>
<times/>
<ci> gamma_Cai </ci>
<ci> Cai </ci>
<apply>
<exp/>
<apply>
<divide/>
<apply>
<times/>
<cn cellml:units="dimensionless"> 2.0 </cn>
<ci> V </ci>
<ci> F </ci>
</apply>
<apply>
<times/>
<ci> R </ci>
<ci> T </ci>
</apply>
</apply>
</apply>
</apply>
<apply>
<times/>
<ci> gamma_Cao </ci>
<ci> Cao </ci>
</apply>
</apply>
<apply>
<minus/>
<apply>
<exp/>
<apply>
<divide/>
<apply>
<times/>
<cn cellml:units="dimensionless"> 2.0 </cn>
<ci> V </ci>
<ci> F </ci>
</apply>
<apply>
<times/>
<ci> R </ci>
<ci> T </ci>
</apply>
</apply>
</apply>
<cn cellml:units="dimensionless"> 1.0 </cn>
</apply>
</apply>
</apply>
</apply>
<apply id="I_CaNa_calculation">
<eq/>
<ci> I_CaNa </ci>
<apply>
<times/>
<ci> P_Na </ci>
<apply>
<power/>
<cn cellml:units="dimensionless"> 1.0 </cn>
<cn cellml:units="dimensionless"> 2.0 </cn>
</apply>
<apply>
<divide/>
<apply>
<times/>
<ci> V </ci>
<apply>
<power/>
<ci> F </ci>
<cn cellml:units="dimensionless"> 2.0 </cn>
</apply>
</apply>
<apply>
<times/>
<ci> R </ci>
<ci> T </ci>
</apply>
</apply>
<apply>
<divide/>
<apply>
<minus/>
<apply>
<times/>
<ci> gamma_Nai </ci>
<ci> Nai </ci>
<apply>
<exp/>
<apply>
<divide/>
<apply>
<times/>
<cn cellml:units="dimensionless"> 1.0 </cn>
<ci> V </ci>
<ci> F </ci>
</apply>
<apply>
<times/>
<ci> R </ci>
<ci> T </ci>
</apply>
</apply>
</apply>
</apply>
<apply>
<times/>
<ci> gamma_Nao </ci>
<ci> Nao </ci>
</apply>
</apply>
<apply>
<minus/>
<apply>
<exp/>
<apply>
<divide/>
<apply>
<times/>
<cn cellml:units="dimensionless"> 1.0 </cn>
<ci> V </ci>
<ci> F </ci>
</apply>
<apply>
<times/>
<ci> R </ci>
<ci> T </ci>
</apply>
</apply>
</apply>
<cn cellml:units="dimensionless"> 1.0 </cn>
</apply>
</apply>
</apply>
</apply>
<apply id="I_CaK_calculation">
<eq/>
<ci> I_CaK </ci>
<apply>
<times/>
<ci> P_K </ci>
<apply>
<power/>
<cn cellml:units="dimensionless"> 1.0 </cn>
<cn cellml:units="dimensionless"> 2.0 </cn>
</apply>
<apply>
<divide/>
<apply>
<times/>
<ci> V </ci>
<apply>
<power/>
<ci> F </ci>
<cn cellml:units="dimensionless"> 2.0 </cn>
</apply>
</apply>
<apply>
<times/>
<ci> R </ci>
<ci> T </ci>
</apply>
</apply>
<apply>
<divide/>
<apply>
<minus/>
<apply>
<times/>
<ci> gamma_Ki </ci>
<ci> Ki </ci>
<apply>
<exp/>
<apply>
<divide/>
<apply>
<times/>
<cn cellml:units="dimensionless"> 1.0 </cn>
<ci> V </ci>
<ci> F </ci>
</apply>
<apply>
<times/>
<ci> R </ci>
<ci> T </ci>
</apply>
</apply>
</apply>
</apply>
<apply>
<times/>
<ci> gamma_Ko </ci>
<ci> Ko </ci>
</apply>
</apply>
<apply>
<minus/>
<apply>
<exp/>
<apply>
<divide/>
<apply>
<times/>
<cn cellml:units="dimensionless"> 1.0 </cn>
<ci> V </ci>
<ci> F </ci>
</apply>
<apply>
<times/>
<ci> R </ci>
<ci> T </ci>
</apply>
</apply>
</apply>
<cn cellml:units="dimensionless"> 1.0 </cn>
</apply>
</apply>
</apply>
</apply>
<apply id="i_Ca_L_calculation">
<eq/>
<ci> i_Ca_L </ci>
<apply> <plus/>
<ci> i_CaCa </ci>
<ci> i_CaK </ci>
<ci> i_CaNa </ci>
</apply>
</apply>
</math>
</component>
<component name="L_type_Ca_channel_d_gate">
<variable units="dimensionless" public_interface="out" name="d"/>
<variable units="per_millisecond" name="alpha_d"/>
<variable units="per_millisecond" name="beta_d"/>
<variable units="dimensionless" name="d_infinity"/>
<variable units="millisecond" name="tau_d"/>
<variable units="millivolt" public_interface="in" name="V"/>
<variable units="millisecond" public_interface="in" name="time"/>
<math xmlns="http://www.w3.org/1998/Math/MathML">
<apply id="alpha_d_calculation">
<eq/>
<ci> alpha_d </ci>
<apply>
<divide/>
<ci> d_infinity </ci>
<ci> tau_d </ci>
</apply>
</apply>
<apply id="d_infinity_calculation">
<eq/>
<ci> d_infinity </ci>
<apply>
<divide/>
<cn cellml:units="dimensionless"> 1.0 </cn>
<apply>
<plus/>
<cn cellml:units="dimensionless"> 1.0 </cn>
<apply>
<exp/>
<apply>
<minus/>
<apply>
<divide/>
<apply>
<plus/>
<ci> V </ci>
<cn cellml:units="millivolt"> 10.0 </cn>
</apply>
<cn cellml:units="millivolt"> 6.24 </cn>
</apply>
</apply>
</apply>
</apply>
</apply>
</apply>
<apply id="tau_d_calculation">
<eq/>
<ci> tau_d </ci>
<apply>
<times/>
<ci> d_infinity </ci>
<apply>
<divide/>
<apply>
<minus/>
<cn cellml:units="dimensionless"> 1.0 </cn>
<apply>
<exp/>
<apply>
<minus/>
<apply>
<divide/>
<apply>
<plus/>
<ci> V </ci>
<cn cellml:units="millivolt"> 10.0 </cn>
</apply>
<cn cellml:units="millivolt"> 6.24 </cn>
</apply>
</apply>
</apply>
</apply>
<apply>
<times/>
<cn cellml:units="per_millivolt_millisecond"> 0.035 </cn>
<apply>
<plus/>
<ci> V </ci>
<cn cellml:units="millivolt"> 10.0 </cn>
</apply>
</apply>
</apply>
</apply>
</apply>
<apply id="beta_d_calculation">
<eq/>
<ci> beta_d </ci>
<apply>
<divide/>
<apply>
<minus/>
<cn cellml:units="dimensionless"> 1.0 </cn>
<ci> d_infinity </ci>
</apply>
<ci> tau_d </ci>
</apply>
</apply>
<apply id="dd_dt">
<eq/>
<apply>
<diff/>
<bvar>
<ci> time </ci>
</bvar>
<ci> d </ci>
</apply>
<apply>
<minus/>
<apply>
<times/>
<ci> alpha_d </ci>
<apply>
<minus/>
<cn cellml:units="dimensionless"> 1.0 </cn>
<ci> d </ci>
</apply>
</apply>
<apply>
<times/>
<ci> beta_d </ci>
<ci> d </ci>
</apply>
</apply>
</apply>
</math>
</component>
<component name="L_type_Ca_channel_f_gate">
<variable units="dimensionless" public_interface="out" name="f"/>
<variable units="per_millisecond" name="alpha_f"/>
<variable units="per_millisecond" name="beta_f"/>
<variable units="dimensionless" name="f_infinity"/>
<variable units="millisecond" name="tau_f"/>
<variable units="millivolt" public_interface="in" name="V"/>
<variable units="millisecond" public_interface="in" name="time"/>
<math xmlns="http://www.w3.org/1998/Math/MathML">
<apply id="alpha_f_calculation">
<eq/>
<ci> alpha_f </ci>
<apply>
<divide/>
<ci> f_infinity </ci>
<ci> tau_f </ci>
</apply>
</apply>
<apply id="f_infinity_calculation">
<eq/>
<ci> f_infinity </ci>
<apply>
<plus/>
<apply>
<divide/>
<cn cellml:units="dimensionless"> 1.0 </cn>
<apply>
<plus/>
<cn cellml:units="dimensionless"> 1.0 </cn>
<apply>
<exp/>
<apply>
<divide/>
<apply>
<plus/>
<ci> V </ci>
<cn cellml:units="millivolt"> 35.06 </cn>
</apply>
<cn cellml:units="millivolt"> 8.6 </cn>
</apply>
</apply>
</apply>
</apply>
<apply>
<divide/>
<cn cellml:units="dimensionless"> 0.6 </cn>
<apply>
<plus/>
<cn cellml:units="dimensionless"> 1.0 </cn>
<apply>
<exp/>
<apply>
<divide/>
<apply>
<minus/>
<cn cellml:units="millivolt"> 50.0 </cn>
<ci> V </ci>
</apply>
<cn cellml:units="millivolt"> 20.0 </cn>
</apply>
</apply>
</apply>
</apply>
</apply>
</apply>
<apply id="tau_f_calculation">
<eq/>
<ci> tau_f </ci>
<apply>
<divide/>
<cn cellml:units="millisecond"> 1.0 </cn>
<apply>
<plus/>
<apply>
<times/>
<cn cellml:units="dimensionless"> 0.0197 </cn>
<apply>
<exp/>
<apply>
<minus/>
<apply>
<power/>
<apply>
<times/>
<cn cellml:units="per_millivolt"> 0.0337 </cn>
<apply>
<plus/>
<ci> V </ci>
<cn cellml:units="millivolt"> 10.0 </cn>
</apply>
</apply>
<cn cellml:units="dimensionless"> 2.0 </cn>
</apply>
</apply>
</apply>
</apply>
<cn cellml:units="dimensionless"> 0.02 </cn>
</apply>
</apply>
</apply>
<apply id="beta_f_calculation">
<eq/>
<ci> beta_f </ci>
<apply>
<divide/>
<apply>
<minus/>
<cn cellml:units="dimensionless"> 1.0 </cn>
<ci> f_infinity </ci>
</apply>
<ci> tau_f </ci>
</apply>
</apply>
<apply id="df_dt">
<eq/>
<apply>
<diff/>
<bvar>
<ci> time </ci>
</bvar>
<ci> f </ci>
</apply>
<apply>
<minus/>
<apply>
<times/>
<ci> alpha_f </ci>
<apply>
<minus/>
<cn cellml:units="dimensionless"> 1.0 </cn>
<ci> f </ci>
</apply>
</apply>
<apply>
<times/>
<ci> beta_f </ci>
<ci> f </ci>
</apply>
</apply>
</apply>
</math>
</component>
<component name="L_type_Ca_channel_f_Ca_gate">
<variable units="dimensionless" public_interface="out" name="f_Ca"/>
<variable units="micromolar" name="Km_Ca" initial_value="0.6"/>
<variable units="millivolt" public_interface="in" name="V"/>
<variable units="millisecond" public_interface="in" name="time"/>
<variable units="micromolar" public_interface="in" name="Cai"/>
<math xmlns="http://www.w3.org/1998/Math/MathML">
<apply id="f_Ca_calculation">
<eq/>
<ci> f_Ca </ci>
<apply>
<divide/>
<cn cellml:units="dimensionless"> 1.0 </cn>
<apply>
<plus/>
<cn cellml:units="dimensionless"> 1.0 </cn>
<apply>
<power/>
<apply>
<divide/>
<ci> Cai </ci>
<ci> Km_Ca </ci>
</apply>
<cn cellml:units="dimensionless"> 2.0 </cn>
</apply>
</apply>
</apply>
</apply>
</math>
</component>
<component name="T_type_Ca_channel">
<variable units="microA_per_microF" public_interface="out" name="i_Ca_T"/>
<variable units="milliS_per_microF" name="g_Ca_T" initial_value="0.05"/>
<variable units="millivolt" name="E_Ca"/>
<variable units="millisecond" public_interface="in" private_interface="out" name="time"/>
<variable units="millivolt" public_interface="in" private_interface="out" name="V"/>
<variable units="micromolar" public_interface="in" name="Cai"/>
<variable units="millimolar" public_interface="in" name="Cao"/>
<variable units="joule_per_kilomole_kelvin" public_interface="in" name="R"/>
<variable units="kelvin" public_interface="in" name="T"/>
<variable units="coulomb_per_mole" public_interface="in" name="F"/>
<variable units="dimensionless" private_interface="in" name="b"/>
<variable units="dimensionless" private_interface="in" name="g"/>
<math xmlns="http://www.w3.org/1998/Math/MathML">
<apply id="i_Ca_T_calculation">
<eq/>
<ci> i_Ca_T </ci>
<apply>
<times/>
<ci> g_Ca_T </ci>
<apply>
<power/>
<ci> b </ci>
<cn cellml:units="dimensionless"> 2.0 </cn>
</apply>
<ci> g </ci>
<apply>
<minus/>
<ci> V </ci>
<ci> E_Ca </ci>
</apply>
</apply>
</apply>
<apply id="E_Ca_calculation">
<eq/>
<ci> E_Ca </ci>
<apply>
<times/>
<apply>
<divide/>
<apply>
<times/>
<ci> R </ci>
<ci> T </ci>
</apply>
<apply>
<times/>
<cn cellml:units="dimensionless"> 2.0 </cn>
<ci> F </ci>
</apply>
</apply>
<apply>
<ln/>
<apply>
<divide/>
<ci> Cao </ci>
<ci> Cai </ci>
</apply>
</apply>
</apply>
</apply>
</math>
</component>
<component name="T_type_Ca_channel_b_gate">
<variable units="dimensionless" public_interface="out" name="b"/>
<variable units="dimensionless" name="b_infinity"/>
<variable units="millisecond" name="tau_b"/>
<variable units="millisecond" public_interface="in" name="time"/>
<variable units="millivolt" public_interface="in" name="V"/>
<math xmlns="http://www.w3.org/1998/Math/MathML">
<apply id="b_diff_eq">
<eq/>
<apply>
<diff/>
<bvar>
<ci> time </ci>
</bvar>
<ci> b </ci>
</apply>
<apply>
<divide/>
<apply>
<minus/>
<ci> b_infinity </ci>
<ci> b </ci>
</apply>
<ci> tau_b </ci>
</apply>
</apply>
<apply id="b_infinity_calculation">
<eq/>
<ci> b_infinity </ci>
<apply>
<divide/>
<cn cellml:units="dimensionless"> 1.0 </cn>
<apply>
<plus/>
<cn cellml:units="dimensionless"> 1.0 </cn>
<apply>
<exp/>
<apply>
<minus/>
<apply>
<divide/>
<apply>
<plus/>
<ci> V </ci>
<cn cellml:units="millivolt"> 14.0 </cn>
</apply>
<cn cellml:units="millivolt"> 10.8 </cn>
</apply>
</apply>
</apply>
</apply>
</apply>
</apply>
<apply id="tau_b_calculation">
<eq/>
<ci> tau_b </ci>
<apply>
<divide/>
<apply>
<plus/>
<cn cellml:units="per_millivolt_millisecond"> 3.7 </cn>
<cn cellml:units="per_millivolt_millisecond"> 6.1 </cn>
</apply>
<apply>
<plus/>
<cn cellml:units="dimensionless"> 1.0 </cn>
<apply>
<exp/>
<apply>
<divide/>
<apply>
<plus/>
<cn cellml:units="millivolt"> 25.0 </cn>
<ci> V </ci>
</apply>
<cn cellml:units="millivolt"> 4.5 </cn>
</apply>
</apply>
</apply>
</apply>
</apply>
</math>
</component>
<component name="T_type_Ca_channel_g_gate">
<variable units="dimensionless" public_interface="out" name="g"/>
<variable units="dimensionless" name="g_infinity"/>
<variable units="millisecond" name="tau_g"/>
<variable units="millisecond" public_interface="in" name="time"/>
<variable units="millivolt" public_interface="in" name="V"/>
<math xmlns="http://www.w3.org/1998/Math/MathML">
<apply id="g_diff_eq">
<eq/>
<apply>
<diff/>
<bvar>
<ci> time </ci>
</bvar>
<ci> g </ci>
</apply>
<apply>
<divide/>
<apply>
<minus/>
<ci> g_infinity </ci>
<ci> g </ci>
</apply>
<ci> tau_g </ci>
</apply>
</apply>
<apply id="g_infinity_calculation">
<eq/>
<ci> g_infinity </ci>
<apply>
<divide/>
<cn cellml:units="dimensionless"> 1.0 </cn>
<apply>
<plus/>
<cn cellml:units="dimensionless"> 1.0 </cn>
<apply>
<exp/>
<apply>
<divide/>
<apply>
<plus/>
<ci> V </ci>
<cn cellml:units="millivolt"> 60.0 </cn>
</apply>
<cn cellml:units="millivolt"> 5.6 </cn>
</apply>
</apply>
</apply>
</apply>
</apply>
<apply id="tau_g_calculation">
<eq/>
<ci> tau_g </ci>
<piecewise>
<piece>
<cn cellml:units="millisecond"> 12.0 </cn>
<apply>
<gt/>
<ci> V </ci>
<cn cellml:units="millivolt"> 0.0 </cn>
</apply>
</piece>
<otherwise>
<apply>
<plus/>
<apply>
<times/>
<cn cellml:units="per_millivolt_millisecond"> -0.875 </cn>
<ci> V </ci>
</apply>
<cn cellml:units="millisecond"> 12.0 </cn>
</apply>
</otherwise>
</piecewise>
</apply>
</math>
</component>
<component name="rapid_time_dependent_potassium_current">
<variable units="microA_per_microF" public_interface="out" name="i_Kr"/>
<variable units="milliS_per_microF" name="g_Kr"/>
<variable units="millivolt" name="E_Kr"/>
<variable units="millisecond" public_interface="in" private_interface="out" name="time"/>
<variable units="millivolt" public_interface="in" private_interface="out" name="V"/>
<variable units="joule_per_kilomole_kelvin" public_interface="in" name="R"/>
<variable units="kelvin" public_interface="in" name="T"/>
<variable units="coulomb_per_mole" public_interface="in" name="F"/>
<variable units="millimolar" public_interface="in" name="Ko"/>
<variable units="millimolar" public_interface="in" name="Ki"/>
<variable units="dimensionless" private_interface="in" name="Xr"/>
<variable units="dimensionless" private_interface="in" name="Rr"/>
<math xmlns="http://www.w3.org/1998/Math/MathML">
<apply id="g_Kr_calculation">
<eq/>
<ci> g_Kr </ci>
<apply>
<times/>
<cn cellml:units="milliS_per_microF"> 0.02614 </cn>
<apply>
<root/>
<apply>
<divide/>
<ci> Ko </ci>
<cn cellml:units="millimolar"> 5.4 </cn>
</apply>
</apply>
</apply>
</apply>
<apply id="E_Kr_calculation">
<eq/>
<ci> E_Kr </ci>
<apply>
<times/>
<apply>
<divide/>
<apply>
<times/>
<ci> R </ci>
<ci> T </ci>
</apply>
<ci> F </ci>
</apply>
<apply>
<ln/>
<apply>
<divide/>
<ci> Ko </ci>
<ci> Ki </ci>
</apply>
</apply>
</apply>
</apply>
<apply id="i_Kr_calculation">
<eq/>
<ci> i_Kr </ci>
<apply>
<times/>
<ci> g_Kr </ci>
<ci> Xr </ci>
<ci> Rr </ci>
<apply>
<minus/>
<ci> V </ci>
<ci> E_Kr </ci>
</apply>
</apply>
</apply>
</math>
</component>
<component name="rapid_time_dependent_potassium_current_Xr_gate">
<variable units="dimensionless" public_interface="out" name="Xr"/>
<variable units="dimensionless" name="Xr_infinity"/>
<variable units="millisecond" name="tau_Xr"/>
<variable units="millivolt" public_interface="in" name="V"/>
<variable units="millisecond" public_interface="in" name="time"/>
<math xmlns="http://www.w3.org/1998/Math/MathML">
<apply id="Xr_diff_eq">
<eq/>
<apply>
<diff/>
<bvar>
<ci> time </ci>
</bvar>
<ci> Xr </ci>
</apply>
<apply>
<divide/>
<apply>
<minus/>
<ci> Xr_infinity </ci>
<ci> Xr </ci>
</apply>
<ci> tau_Xr </ci>
</apply>
</apply>
<apply id="Xr_infinity_calculation">
<eq/>
<ci> Xr_infinity </ci>
<apply>
<divide/>
<cn cellml:units="dimensionless"> 1.0 </cn>
<apply>
<plus/>
<cn cellml:units="dimensionless"> 1.0 </cn>
<apply>
<exp/>
<apply>
<minus/>
<apply>
<divide/>
<apply>
<plus/>
<ci> V </ci>
<cn cellml:units="millivolt"> 21.5 </cn>
</apply>
<cn cellml:units="millivolt"> 7.5 </cn>
</apply>
</apply>
</apply>
</apply>
</apply>
</apply>
<apply id="tau_Xr_calculation">
<eq/>
<ci> tau_Xr </ci>
<apply>
<divide/>
<cn cellml:units="dimensionless"> 1.0 </cn>
<apply>
<plus/>
<apply>
<divide/>
<apply>
<times/>
<cn cellml:units="dimensionless"> 0.00138 </cn>
<apply>
<plus/>
<ci> V </ci>
<cn cellml:units="millivolt"> 14.2 </cn>
</apply>
</apply>
<apply>
<minus/>
<cn cellml:units="dimensionless"> 1.0 </cn>
<apply>
<exp/>
<apply>
<times/>
<cn cellml:units="dimensionless"> -0.123 </cn>
<apply>
<plus/>
<ci> V </ci>
<cn cellml:units="millivolt"> 14.2 </cn>
</apply>
</apply>
</apply>
</apply>
</apply>
<apply>
<divide/>
<apply>
<times/>
<cn cellml:units="dimensionless"> 0.00061 </cn>
<apply>
<plus/>
<ci> V </ci>
<cn cellml:units="millivolt"> 38.9 </cn>
</apply>
</apply>
<apply>
<minus/>
<apply>
<exp/>
<apply>
<times/>
<cn cellml:units="dimensionless"> 0.145 </cn>
<apply>
<plus/>
<ci> V </ci>
<cn cellml:units="millivolt"> 38.9 </cn>
</apply>
</apply>
</apply>
<cn cellml:units="dimensionless"> 1.0 </cn>
</apply>
</apply>
</apply>
</apply>
</apply>
</math>
</component>
<component name="rapid_time_dependent_potassium_current_Rr_gate">
<variable units="dimensionless" public_interface="out" name="Rr"/>
<variable units="millivolt" public_interface="in" name="V"/>
<variable units="millisecond" public_interface="in" name="time"/>
<math xmlns="http://www.w3.org/1998/Math/MathML">
<apply id="Rr_calculation">
<eq/>
<ci> Rr </ci>
<apply>
<divide/>
<cn cellml:units="dimensionless"> 1.0 </cn>
<apply>
<plus/>
<cn cellml:units="dimensionless"> 1.0 </cn>
<apply>
<exp/>
<apply>
<divide/>
<apply>
<plus/>
<ci> V </ci>
<cn cellml:units="millivolt"> 9.0 </cn>
</apply>
<cn cellml:units="millivolt"> 22.4 </cn>
</apply>
</apply>
</apply>
</apply>
</apply>
</math>
</component>
<component name="slow_time_dependent_potassium_current">
<variable units="microA_per_microF" public_interface="out" name="i_Ks"/>
<variable units="milliS_per_microF" name="g_Ks"/>
<variable units="millivolt" name="E_Ks"/>
<variable units="dimensionless" name="P_NaK" initial_value="0.01833"/>
<variable units="millisecond" public_interface="in" private_interface="out" name="time"/>
<variable units="millivolt" public_interface="in" private_interface="out" name="V"/>
<variable units="millimolar" public_interface="in" name="Ko"/>
<variable units="millimolar" public_interface="in" name="Ki"/>
<variable units="millimolar" public_interface="in" name="Nao"/>
<variable units="millimolar" public_interface="in" name="Nai"/>
<variable units="micromolar" public_interface="in" name="Cai"/>
<variable units="joule_per_kilomole_kelvin" public_interface="in" name="R"/>
<variable units="kelvin" public_interface="in" name="T"/>
<variable units="coulomb_per_mole" public_interface="in" name="F"/>
<variable units="dimensionless" private_interface="in" name="Xs1"/>
<variable units="dimensionless" private_interface="in" name="Xs2"/>
<math xmlns="http://www.w3.org/1998/Math/MathML">
<apply id="g_Ks_calculation">
<eq/>
<ci> g_Ks </ci>
<apply>
<times/>
<cn cellml:units="dimensionless"> 0.433 </cn>
<apply>
<divide/>
<apply>
<plus/>
<cn cellml:units="dimensionless"> 1.0 </cn>
<cn cellml:units="dimensionless"> 0.6 </cn>
</apply>
<apply>
<plus/>
<cn cellml:units="dimensionless"> 1.0 </cn>
<apply>
<power/>
<apply>
<divide/>
<cn cellml:units="micromolar"> 0.000038 </cn>
<ci> Cai </ci>
</apply>
<cn cellml:units="dimensionless"> 1.4 </cn>
</apply>
</apply>
</apply>
</apply>
</apply>
<apply id="E_Ks_calculation">
<eq/>
<ci> E_Ks </ci>
<apply>
<times/>
<apply>
<divide/>
<apply>
<times/>
<ci> R </ci>
<ci> T </ci>
</apply>
<ci> F </ci>
</apply>
<apply>
<ln/>
<apply>
<divide/>
<apply>
<plus/>
<ci> Ko </ci>
<apply>
<times/>
<ci> P_NaK </ci>
<ci> Nao </ci>
</apply>
</apply>
<apply>
<plus/>
<ci> Ki </ci>
<apply>
<times/>
<ci> P_NaK </ci>
<ci> Nai </ci>
</apply>
</apply>
</apply>
</apply>
</apply>
</apply>
<apply id="i_Ks_calculation">
<eq/>
<ci> i_Ks </ci>
<apply>
<times/>
<ci> g_Ks </ci>
<ci> Xs1 </ci>
<ci> Xs2 </ci>
<apply>
<minus/>
<ci> V </ci>
<ci> E_Ks </ci>
</apply>
</apply>
</apply>
</math>
</component>
<component name="slow_time_dependent_potassium_current_Xs1_gate">
<variable units="dimensionless" public_interface="out" name="Xs1"/>
<variable units="millisecond" public_interface="out" name="tau_Xs1"/>
<variable units="dimensionless" public_interface="out" name="Xs_infinity"/>
<variable units="millivolt" public_interface="in" name="V"/>
<variable units="millisecond" public_interface="in" name="time"/>
<math xmlns="http://www.w3.org/1998/Math/MathML">
<apply id="Xs1_diff_eq">
<eq/>
<apply>
<diff/>
<bvar>
<ci> time </ci>
</bvar>
<ci> Xs1 </ci>
</apply>
<apply>
<divide/>
<apply>
<minus/>
<ci> Xs_infinity </ci>
<ci> Xs1 </ci>
</apply>
<ci> tau_Xs1 </ci>
</apply>
</apply>
<apply id="Xs_infinity_calculation">
<eq/>
<ci> Xs_infinity </ci>
<apply>
<divide/>
<cn cellml:units="dimensionless"> 1.0 </cn>
<apply>
<plus/>
<cn cellml:units="dimensionless"> 1.0 </cn>
<apply>
<exp/>
<apply>
<minus/>
<apply>
<divide/>
<apply>
<minus/>
<ci> V </ci>
<cn cellml:units="millivolt"> 1.5 </cn>
</apply>
<cn cellml:units="millivolt"> 16.7 </cn>
</apply>
</apply>
</apply>
</apply>
</apply>
</apply>
<apply id="tau_Xs1_calculation">
<eq/>
<ci> tau_Xs1 </ci>
<apply>
<divide/>
<cn cellml:units="dimensionless"> 1.0 </cn>
<apply>
<plus/>
<apply>
<divide/>
<apply>
<times/>
<cn cellml:units="dimensionless"> 0.0000719 </cn>
<apply>
<plus/>
<ci> V </ci>
<cn cellml:units="millivolt"> 30.0 </cn>
</apply>
</apply>
<apply>
<minus/>
<cn cellml:units="dimensionless"> 1.0 </cn>
<apply>
<exp/>
<apply>
<times/>
<cn cellml:units="dimensionless"> -0.148 </cn>
<apply>
<plus/>
<ci> V </ci>
<cn cellml:units="millivolt"> 30.0 </cn>
</apply>
</apply>
</apply>
</apply>
</apply>
<apply>
<divide/>
<apply>
<times/>
<cn cellml:units="dimensionless"> 0.000131 </cn>
<apply>
<plus/>
<ci> V </ci>
<cn cellml:units="millivolt"> 30.0 </cn>
</apply>
</apply>
<apply>
<minus/>
<apply>
<exp/>
<apply>
<times/>
<cn cellml:units="dimensionless"> 0.0687 </cn>
<apply>
<plus/>
<ci> V </ci>
<cn cellml:units="millivolt"> 30.0 </cn>
</apply>
</apply>
</apply>
<cn cellml:units="dimensionless"> 1.0 </cn>
</apply>
</apply>
</apply>
</apply>
</apply>
</math>
</component>
<component name="slow_time_dependent_potassium_current_Xs2_gate">
<variable units="dimensionless" public_interface="out" name="Xs2"/>
<variable units="millisecond" name="tau_Xs2"/>
<variable units="millivolt" public_interface="in" name="V"/>
<variable units="millisecond" public_interface="in" name="time"/>
<variable units="millisecond" public_interface="in" name="tau_Xs1"/>
<variable units="dimensionless" public_interface="in" name="Xs_infinity"/>
<math xmlns="http://www.w3.org/1998/Math/MathML">
<apply id="Xs2_diff_eq">
<eq/>
<apply>
<diff/>
<bvar>
<ci> time </ci>
</bvar>
<ci> Xs2 </ci>
</apply>
<apply>
<divide/>
<apply>
<minus/>
<ci> Xs_infinity </ci>
<ci> Xs2 </ci>
</apply>
<ci> tau_Xs2 </ci>
</apply>
</apply>
<apply id="tau_Xs2_calculation">
<eq/>
<ci> tau_Xs2 </ci>
<apply>
<times/>
<cn cellml:units="dimensionless"> 4.0 </cn>
<ci> tau_Xs1 </ci>
</apply>
</apply>
</math>
</component>
<component name="time_independent_potassium_current">
<variable units="microA_per_microF" public_interface="out" name="i_K1"/>
<variable units="millivolt" public_interface="out" private_interface="out" name="E_K1"/>
<variable units="milliS_per_cm2" name="g_K1"/>
<variable units="millisecond" public_interface="in" private_interface="out" name="time"/>
<variable units="millivolt" public_interface="in" private_interface="out" name="V"/>
<variable units="millimolar" public_interface="in" name="Ko"/>
<variable units="millimolar" public_interface="in" name="Ki"/>
<variable units="joule_per_kilomole_kelvin" public_interface="in" name="R"/>
<variable units="kelvin" public_interface="in" name="T"/>
<variable units="coulomb_per_mole" public_interface="in" name="F"/>
<variable units="dimensionless" private_interface="in" name="K1_infinity"/>
<math xmlns="http://www.w3.org/1998/Math/MathML">
<apply id="g_K1_calculation">
<eq/>
<ci> g_K1 </ci>
<apply>
<times/>
<cn cellml:units="milliS_per_microF"> 0.75 </cn>
<apply>
<root/>
<apply>
<divide/>
<ci> Ko </ci>
<cn cellml:units="millimolar"> 5.4 </cn>
</apply>
</apply>
</apply>
</apply>
<apply id="E_K1_calculation">
<eq/>
<ci> E_K1 </ci>
<apply>
<times/>
<apply>
<divide/>
<apply>
<times/>
<ci> R </ci>
<ci> T </ci>
</apply>
<ci> F </ci>
</apply>
<apply>
<ln/>
<apply>
<divide/>
<ci> Ko </ci>
<ci> Ki </ci>
</apply>
</apply>
</apply>
</apply>
<apply id="i_K1_calculation">
<eq/>
<ci> i_K1 </ci>
<apply>
<times/>
<ci> g_K1 </ci>
<ci> K1_infinity </ci>
<apply>
<minus/>
<ci> V </ci>
<ci> E_K1 </ci>
</apply>
</apply>
</apply>
</math>
</component>
<component name="time_independent_potassium_current_K1_gate">
<variable units="dimensionless" public_interface="out" name="K1_infinity"/>
<variable units="per_millisecond" name="alpha_K1"/>
<variable units="per_millisecond" name="beta_K1"/>
<variable units="millivolt" public_interface="in" name="V"/>
<variable units="millisecond" public_interface="in" name="time"/>
<variable units="millivolt" public_interface="in" name="E_K1"/>
<math xmlns="http://www.w3.org/1998/Math/MathML">
<apply id="alpha_K1_calculation">
<eq/>
<ci> alpha_K1 </ci>
<apply>
<divide/>
<cn cellml:units="per_millisecond"> 1.02 </cn>
<apply>
<plus/>
<cn cellml:units="dimensionless"> 1.0 </cn>
<apply>
<exp/>
<apply>
<times/>
<cn cellml:units="per_millivolt"> 0.2385 </cn>
<apply>
<minus/>
<apply>
<minus/>
<ci> V </ci>
<ci> E_K1 </ci>
</apply>
<cn cellml:units="millivolt"> 59.215 </cn>
</apply>
</apply>
</apply>
</apply>
</apply>
</apply>
<apply id="beta_K1_calculation">
<eq/>
<ci> beta_K1 </ci>
<apply>
<divide/>
<apply>
<plus/>
<apply>
<times/>
<cn cellml:units="per_millisecond"> 0.49124 </cn>
<apply>
<exp/>
<apply>
<times/>
<cn cellml:units="dimensionless"> 0.08032 </cn>
<apply>
<minus/>
<apply>
<plus/>
<ci> V </ci>
<cn cellml:units="millivolt"> 5.476 </cn>
</apply>
<ci> E_K1 </ci>
</apply>
</apply>
</apply>
</apply>
<apply>
<exp/>
<apply>
<times/>
<cn cellml:units="dimensionless"> 0.06175 </cn>
<apply>
<minus/>
<ci> V </ci>
<apply>
<plus/>
<ci> E_K1 </ci>
<cn cellml:units="millivolt"> 594.31 </cn>
</apply>
</apply>
</apply>
</apply>
</apply>
<apply>
<plus/>
<cn cellml:units="dimensionless"> 1.0 </cn>
<apply>
<exp/>
<apply>
<times/>
<cn cellml:units="per_millivolt"> -0.5143 </cn>
<apply>
<minus/>
<ci> V </ci>
<apply>
<plus/>
<ci> E_K1 </ci>
<cn cellml:units="millivolt"> 4.753 </cn>
</apply>
</apply>
</apply>
</apply>
</apply>
</apply>
</apply>
<apply id="K1_infinity_calculation">
<eq/>
<ci> K1_infinity </ci>
<apply>
<divide/>
<ci> alpha_K1 </ci>
<apply>
<plus/>
<ci> alpha_K1 </ci>
<ci> beta_K1 </ci>
</apply>
</apply>
</apply>
</math>
</component>
<component name="plateau_potassium_current">
<variable units="microA_per_microF" public_interface="out" name="i_Kp"/>
<variable units="millivolt" name="E_Kp"/>
<variable units="milliS_per_microF" name="g_Kp" initial_value="0.0183"/>
<variable units="dimensionless" name="Kp"/>
<variable units="millisecond" public_interface="in" name="time"/>
<variable units="millivolt" public_interface="in" name="V"/>
<variable units="millivolt" public_interface="in" name="E_K1"/>
<math xmlns="http://www.w3.org/1998/Math/MathML">
<apply id="E_Kp_calculation">
<eq/>
<ci> E_Kp </ci>
<ci> E_K1 </ci>
</apply>
<apply id="Kp_calculation">
<eq/>
<ci> Kp </ci>
<apply>
<divide/>
<cn cellml:units="dimensionless"> 1.0 </cn>
<apply>
<plus/>
<cn cellml:units="dimensionless"> 1.0 </cn>
<apply>
<exp/>
<apply>
<divide/>
<apply>
<minus/>
<cn cellml:units="millivolt"> 7.488 </cn>
<ci> V </ci>
</apply>
<cn cellml:units="millivolt"> 5.98 </cn>
</apply>
</apply>
</apply>
</apply>
</apply>
<apply id="i_Kp_calculation">
<eq/>
<ci> i_Kp </ci>
<apply>
<times/>
<ci> g_Kp </ci>
<ci> Kp </ci>
<apply>
<minus/>
<ci> V </ci>
<ci> E_Kp </ci>
</apply>
</apply>
</apply>
</math>
</component>
<component name="sarcolemmal_calcium_pump">
<variable units="microA_per_microF" public_interface="out" name="i_p_Ca"/>
<variable units="micromolar" name="K_mpCa" initial_value="0.5"/>
<variable units="microA_per_microF" name="I_pCa" initial_value="1.15"/>
<variable units="millisecond" public_interface="in" name="time"/>
<variable units="micromolar" public_interface="in" name="Cai"/>
<math xmlns="http://www.w3.org/1998/Math/MathML">
<apply id="i_p_Ca_calculation">
<eq/>
<ci> i_p_Ca </ci>
<apply>
<times/>
<ci> I_pCa </ci>
<apply>
<divide/>
<ci> Cai </ci>
<apply>
<plus/>
<ci> K_mpCa </ci>
<ci> Cai </ci>
</apply>
</apply>
</apply>
</apply>
</math>
</component>
<component name="sodium_background_current">
<variable units="microA_per_microF" public_interface="out" name="i_Na_b"/>
<variable units="milliS_per_microF" name="g_Nab" initial_value="0.00141"/>
<variable units="millivolt" name="E_NaN"/>
<variable units="millisecond" public_interface="in" name="time"/>
<variable units="millivolt" public_interface="in" name="V"/>
<variable units="millivolt" public_interface="in" name="E_Na"/>
<math xmlns="http://www.w3.org/1998/Math/MathML">
<apply id="E_NaN_calculation">
<eq/>
<ci> E_NaN </ci>
<ci> E_Na </ci>
</apply>
<apply id="i_Na_b_calculation">
<eq/>
<ci> i_Na_b </ci>
<apply>
<times/>
<ci> g_Nab </ci>
<apply>
<minus/>
<ci> V </ci>
<ci> E_NaN </ci>
</apply>
</apply>
</apply>
</math>
</component>
<component name="calcium_background_current">
<variable units="microA_per_microF" public_interface="out" name="i_Ca_b"/>
<variable units="milliS_per_microF" name="g_Cab" initial_value="0.003016"/>
<variable units="millivolt" name="E_CaN"/>
<variable units="millisecond" public_interface="in" name="time"/>
<variable units="millivolt" public_interface="in" name="V"/>
<variable units="joule_per_kilomole_kelvin" public_interface="in" name="R"/>
<variable units="kelvin" public_interface="in" name="T"/>
<variable units="coulomb_per_mole" public_interface="in" name="F"/>
<variable units="micromolar" public_interface="in" name="Cai"/>
<variable units="millimolar" public_interface="in" name="Cao"/>
<math xmlns="http://www.w3.org/1998/Math/MathML">
<apply id="E_CaN_calculation">
<eq/>
<ci> E_CaN </ci>
<apply>
<times/>
<apply>
<divide/>
<apply>
<times/>
<ci> R </ci>
<ci> T </ci>
</apply>
<apply>
<times/>
<cn cellml:units="dimensionless"> 2.0 </cn>
<ci> F </ci>
</apply>
</apply>
<apply>
<ln/>
<apply>
<divide/>
<ci> Cao </ci>
<ci> Cai </ci>
</apply>
</apply>
</apply>
</apply>
<apply id="i_Ca_b_calculation">
<eq/>
<ci> i_Ca_b </ci>
<apply>
<times/>
<ci> g_Cab </ci>
<apply>
<minus/>
<ci> V </ci>
<ci> E_CaN </ci>
</apply>
</apply>
</apply>
</math>
</component>
<component name="sodium_potassium_pump">
<variable units="microA_per_microF" public_interface="out" name="i_NaK"/>
<variable units="microA_per_microF" name="I_NaK" initial_value="1.5e-2"/>
<variable units="dimensionless" name="f_NaK"/>
<variable units="millimolar" name="K_mNai" initial_value="10.0"/>
<variable units="millimolar" name="K_mKo" initial_value="1.5"/>
<variable units="dimensionless" name="sigma"/>
<variable units="millisecond" public_interface="in" name="time"/>
<variable units="millivolt" public_interface="in" name="V"/>
<variable units="joule_per_kilomole_kelvin" public_interface="in" name="R"/>
<variable units="kelvin" public_interface="in" name="T"/>
<variable units="coulomb_per_mole" public_interface="in" name="F"/>
<variable units="millimolar" public_interface="in" name="Nai"/>
<variable units="millimolar" public_interface="in" name="Nao"/>
<variable units="millimolar" public_interface="in" name="Ko"/>
<math xmlns="http://www.w3.org/1998/Math/MathML">
<apply id="f_NaK_calculation">
<eq/>
<ci> f_NaK </ci>
<apply>
<divide/>
<cn cellml:units="dimensionless"> 1.0 </cn>
<apply>
<plus/>
<apply>
<plus/>
<cn cellml:units="dimensionless"> 1.0 </cn>
<apply>
<times/>
<cn cellml:units="dimensionless"> 0.1245 </cn>
<apply>
<exp/>
<apply>
<times/>
<cn cellml:units="dimensionless"> -0.1 </cn>
<apply>
<divide/>
<apply>
<times/>
<ci> V </ci>
<ci> F </ci>
</apply>
<apply>
<times/>
<ci> R </ci>
<ci> T </ci>
</apply>
</apply>
</apply>
</apply>
</apply>
</apply>
<apply>
<times/>
<cn cellml:units="dimensionless"> 0.0365 </cn>
<ci> sigma </ci>
<apply>
<exp/>
<apply>
<minus/>
<apply>
<divide/>
<apply>
<times/>
<ci> V </ci>
<ci> F </ci>
</apply>
<apply>
<times/>
<ci> R </ci>
<ci> T </ci>
</apply>
</apply>
</apply>
</apply>
</apply>
</apply>
</apply>
</apply>
<apply id="sigma_calculation">
<eq/>
<ci> sigma </ci>
<apply>
<times/>
<apply>
<divide/>
<cn cellml:units="dimensionless"> 1.0 </cn>
<cn cellml:units="dimensionless"> 7.0 </cn>
</apply>
<apply>
<minus/>
<apply>
<exp/>
<apply>
<divide/>
<ci> Nao </ci>
<cn cellml:units="dimensionless"> 67.3 </cn>
</apply>
</apply>
<cn cellml:units="dimensionless"> 1.0 </cn>
</apply>
</apply>
</apply>
<apply id="i_NaK_calculation">
<eq/>
<ci> i_NaK </ci>
<apply>
<times/>
<ci> I_NaK </ci>
<ci> f_NaK </ci>
<apply>
<divide/>
<cn cellml:units="dimensionless"> 1.0 </cn>
<apply>
<plus/>
<cn cellml:units="dimensionless"> 1.0 </cn>
<apply>
<power/>
<apply>
<divide/>
<ci> K_mNai </ci>
<ci> Nai </ci>
</apply>
<cn cellml:units="dimensionless"> 1.5 </cn>
</apply>
</apply>
</apply>
<apply>
<divide/>
<ci> Ko </ci>
<apply>
<plus/>
<ci> Ko </ci>
<ci> K_mKo </ci>
</apply>
</apply>
</apply>
</apply>
</math>
</component>
<component name="non_specific_calcium_activated_current">
<variable units="microA_per_microF" public_interface="out" name="i_ns_Ca"/>
<variable units="microA_per_microF" public_interface="out" name="i_ns_Na"/>
<variable units="microA_per_microF" public_interface="out" name="i_ns_K"/>
<variable units="cm_per_second" name="P_ns_Ca" initial_value="1.75E-7"/>
<variable units="dimensionless" public_interface="in" name="gamma_Nai"/>
<variable units="dimensionless" public_interface="in" name="gamma_Nao"/>
<variable units="dimensionless" public_interface="in" name="gamma_Ki"/>
<variable units="dimensionless" public_interface="in" name="gamma_Ko"/>
<variable units="joule_per_kilomole_kelvin" public_interface="in" name="R"/>
<variable units="kelvin" public_interface="in" name="T"/>
<variable units="coulomb_per_mole" public_interface="in" name="F"/>
<variable units="millimolar" public_interface="in" name="Cao"/>
<variable units="millimolar" public_interface="in" name="Nao"/>
<variable units="millimolar" public_interface="in" name="Ko"/>
<variable units="millimolar" public_interface="in" name="Nai"/>
<variable units="millimolar" public_interface="in" name="Ki"/>
<variable units="microA_per_microF" name="I_ns_Na"/>
<variable units="microA_per_microF" name="I_ns_K"/>
<variable units="micromolar" name="K_m_ns_Ca" initial_value="1.2"/>
<variable units="millisecond" public_interface="in" name="time"/>
<variable units="micromolar" public_interface="in" name="Cai"/>
<variable units="millivolt" public_interface="in" name="V"/>
<math xmlns="http://www.w3.org/1998/Math/MathML">
<apply id="i_ns_Na_calculation">
<eq/>
<ci> i_ns_Na </ci>
<apply>
<times/>
<ci> I_ns_Na </ci>
<apply>
<divide/>
<cn cellml:units="dimensionless"> 1.0 </cn>
<apply>
<plus/>
<cn cellml:units="dimensionless"> 1.0 </cn>
<apply>
<power/>
<apply>
<divide/>
<ci> K_m_ns_Ca </ci>
<ci> Cai </ci>
</apply>
<cn cellml:units="dimensionless"> 3.0 </cn>
</apply>
</apply>
</apply>
</apply>
</apply>
<apply id="i_ns_K_calculation">
<eq/>
<ci> i_ns_K </ci>
<apply>
<times/>
<ci> I_ns_K </ci>
<apply>
<divide/>
<cn cellml:units="dimensionless"> 1.0 </cn>
<apply>
<plus/>
<cn cellml:units="dimensionless"> 1.0 </cn>
<apply>
<power/>
<apply>
<divide/>
<ci> K_m_ns_Ca </ci>
<ci> Cai </ci>
</apply>
<cn cellml:units="dimensionless"> 3.0 </cn>
</apply>
</apply>
</apply>
</apply>
</apply>
<apply id="i_ns_Ca_calculation">
<eq/>
<ci> i_ns_Ca </ci>
<apply>
<plus/>
<ci> i_ns_Na </ci>
<ci> i_ns_K </ci>
</apply>
</apply>
<apply id="I_ns_Na_calculation">
<eq/>
<ci> I_ns_Na </ci>
<apply>
<times/>
<ci> P_ns_Ca </ci>
<apply>
<power/>
<cn cellml:units="dimensionless"> 1.0 </cn>
<cn cellml:units="dimensionless"> 2.0 </cn>
</apply>
<apply>
<divide/>
<apply>
<times/>
<ci> V </ci>
<apply>
<power/>
<ci> F </ci>
<cn cellml:units="dimensionless"> 2.0 </cn>
</apply>
</apply>
<apply>
<times/>
<ci> R </ci>
<ci> T </ci>
</apply>
</apply>
<apply>
<divide/>
<apply>
<minus/>
<apply>
<times/>
<ci> gamma_Nai </ci>
<ci> Nai </ci>
<apply>
<exp/>
<apply>
<divide/>
<apply>
<times/>
<cn cellml:units="dimensionless"> 1.0 </cn>
<ci> V </ci>
<ci> F </ci>
</apply>
<apply>
<times/>
<ci> R </ci>
<ci> T </ci>
</apply>
</apply>
</apply>
</apply>
<apply>
<times/>
<ci> gamma_Nao </ci>
<ci> Nao </ci>
</apply>
</apply>
<apply>
<minus/>
<apply>
<exp/>
<apply>
<divide/>
<apply>
<times/>
<cn cellml:units="dimensionless"> 1.0 </cn>
<ci> V </ci>
<ci> F </ci>
</apply>
<apply>
<times/>
<ci> R </ci>
<ci> T </ci>
</apply>
</apply>
</apply>
<cn cellml:units="dimensionless"> 1.0 </cn>
</apply>
</apply>
</apply>
</apply>
<apply id="I_ns_K_calculation">
<eq/>
<ci> I_ns_K </ci>
<apply>
<times/>
<ci> P_ns_Ca </ci>
<apply>
<power/>
<cn cellml:units="dimensionless"> 1.0 </cn>
<cn cellml:units="dimensionless"> 2.0 </cn>
</apply>
<apply>
<divide/>
<apply>
<times/>
<ci> V </ci>
<apply>
<power/>
<ci> F </ci>
<cn cellml:units="dimensionless"> 2.0 </cn>
</apply>
</apply>
<apply>
<times/>
<ci> R </ci>
<ci> T </ci>
</apply>
</apply>
<apply>
<divide/>
<apply>
<minus/>
<apply>
<times/>
<ci> gamma_Ki </ci>
<ci> Ki </ci>
<apply>
<exp/>
<apply>
<divide/>
<apply>
<times/>
<cn cellml:units="dimensionless"> 1.0 </cn>
<ci> V </ci>
<ci> F </ci>
</apply>
<apply>
<times/>
<ci> R </ci>
<ci> T </ci>
</apply>
</apply>
</apply>
</apply>
<apply>
<times/>
<ci> gamma_Ko </ci>
<ci> Ko </ci>
</apply>
</apply>
<apply>
<minus/>
<apply>
<exp/>
<apply>
<divide/>
<apply>
<times/>
<cn cellml:units="dimensionless"> 1.0 </cn>
<ci> V </ci>
<ci> F </ci>
</apply>
<apply>
<times/>
<ci> R </ci>
<ci> T </ci>
</apply>
</apply>
</apply>
<cn cellml:units="dimensionless"> 1.0 </cn>
</apply>
</apply>
</apply>
</apply>
</math>
</component>
<component name="ATP_dependent_potassium_current">
<variable units="microA_per_microF" public_interface="out" name="i_K_ATP"/>
<variable units="millivolt" public_interface="out" name="E_K"/>
<variable units="milliS_per_microF" name="g_K_ATP"/>
<variable units="nanoS_per_cm2" name="G_K_ATP"/>
<variable units="dimensionless" name="P_ATP"/>
<variable units="millimolar" name="Ko_normal" initial_value="4.0"/>
<variable units="micromolar" name="K_05" initial_value="0.250"/>
<variable units="millimolar" name="ATP_i" initial_value="3.0"/>
<variable units="dimensionless" name="n" initial_value="0.24"/>
<variable units="dimensionless" name="H" initial_value="2.0"/>
<variable units="cm2" name="Nichols_area" initial_value="0.005"/>
<variable units="millisecond" public_interface="in" name="time"/>
<variable units="millivolt" public_interface="in" name="V"/>
<variable units="millimolar" public_interface="in" name="Ko"/>
<variable units="millimolar" public_interface="in" name="Ki"/>
<variable units="joule_per_kilomole_kelvin" public_interface="in" name="R"/>
<variable units="kelvin" public_interface="in" name="T"/>
<variable units="coulomb_per_mole" public_interface="in" name="F"/>
<math xmlns="http://www.w3.org/1998/Math/MathML">
<apply id="i_K_ATP_calculation">
<eq/>
<ci> i_K_ATP </ci>
<apply>
<times/>
<ci> g_K_ATP </ci>
<apply>
<minus/>
<ci> V </ci>
<ci> E_K </ci>
</apply>
</apply>
</apply>
<apply id="g_K_ATP_calculation">
<eq/>
<ci> g_K_ATP </ci>
<apply>
<times/>
<ci> G_K_ATP </ci>
<ci> P_ATP </ci>
<apply>
<power/>
<apply>
<divide/>
<ci> Ko </ci>
<ci> Ko_normal </ci>
</apply>
<ci> n </ci>
</apply>
</apply>
</apply>
<apply id="E_K_calculation">
<eq/>
<ci> E_K </ci>
<apply>
<times/>
<apply>
<divide/>
<apply>
<times/>
<ci> R </ci>
<ci> T </ci>
</apply>
<ci> F </ci>
</apply>
<apply>
<ln/>
<apply>
<divide/>
<ci> Ko </ci>
<ci> Ki </ci>
</apply>
</apply>
</apply>
</apply>
<apply id="G_K_ATP_calculation">
<eq/>
<ci> G_K_ATP </ci>
<apply>
<divide/>
<cn cellml:units="dimensionless"> 0.000195 </cn>
<ci> Nichols_area </ci>
</apply>
</apply>
<apply id="P_ATP_calculation">
<eq/>
<ci> P_ATP </ci>
<apply>
<divide/>
<cn cellml:units="dimensionless"> 1.0 </cn>
<apply>
<plus/>
<cn cellml:units="dimensionless"> 1.0 </cn>
<apply>
<power/>
<apply>
<divide/>
<ci> ATP_i </ci>
<ci> K_05 </ci>
</apply>
<ci> H </ci>
</apply>
</apply>
</apply>
</apply>
</math>
</component>
<component name="Na_Ca_exchanger">
<variable units="microA_per_microF" public_interface="out" name="i_NaCa"/>
<variable units="microA_per_microF" name="K_NaCa" initial_value="2000.0"/>
<variable units="millimolar" name="K_mNa" initial_value="87.5"/>
<variable units="millimolar" name="K_mCa" initial_value="1.38"/>
<variable units="dimensionless" name="K_sat" initial_value="0.1"/>
<variable units="dimensionless" name="eta" initial_value="0.35"/>
<variable units="millisecond" public_interface="in" name="time"/>
<variable units="millivolt" public_interface="in" name="V"/>
<variable units="joule_per_kilomole_kelvin" public_interface="in" name="R"/>
<variable units="kelvin" public_interface="in" name="T"/>
<variable units="coulomb_per_mole" public_interface="in" name="F"/>
<variable units="millimolar" public_interface="in" name="Nai"/>
<variable units="millimolar" public_interface="in" name="Nao"/>
<variable units="micromolar" public_interface="in" name="Cai"/>
<variable units="millimolar" public_interface="in" name="Cao"/>
<math xmlns="http://www.w3.org/1998/Math/MathML">
<apply id="Na_Ca_exchanger">
<eq/>
<ci> i_NaCa </ci>
<apply>
<times/>
<ci> K_NaCa </ci>
<apply>
<divide/>
<cn cellml:units="dimensionless"> 1.0 </cn>
<apply>
<plus/>
<apply>
<power/>
<ci> K_mNa </ci>
<cn cellml:units="dimensionless"> 3.0 </cn>
</apply>
<apply>
<power/>
<ci> Nao </ci>
<cn cellml:units="dimensionless"> 3.0 </cn>
</apply>
</apply>
</apply>
<apply>
<divide/>
<cn cellml:units="dimensionless"> 1.0 </cn>
<apply>
<plus/>
<ci> K_mCa </ci>
<ci> Cao </ci>
</apply>
</apply>
<apply>
<divide/>
<cn cellml:units="dimensionless"> 1.0 </cn>
<apply>
<plus/>
<cn cellml:units="dimensionless"> 1.0 </cn>
<apply>
<times/>
<ci> K_sat </ci>
<apply>
<exp/>
<apply>
<times/>
<apply>
<minus/>
<ci> eta </ci>
<cn cellml:units="dimensionless"> 1.0 </cn>
</apply>
<ci> V </ci>
<apply>
<divide/>
<ci> F </ci>
<apply>
<times/>
<ci> R </ci>
<ci> T </ci>
</apply>
</apply>
</apply>
</apply>
</apply>
</apply>
</apply>
<apply>
<minus/>
<apply>
<times/>
<apply>
<exp/>
<apply>
<times/>
<ci> eta </ci>
<ci> V </ci>
<apply>
<divide/>
<ci> F </ci>
<apply>
<times/>
<ci> R </ci>
<ci> T </ci>
</apply>
</apply>
</apply>
</apply>
<apply>
<power/>
<ci> Nai </ci>
<cn cellml:units="dimensionless"> 3.0 </cn>
</apply>
<ci> Cao </ci>
</apply>
<apply>
<times/>
<apply>
<exp/>
<apply>
<times/>
<apply>
<minus/>
<ci> eta </ci>
<cn cellml:units="dimensionless"> 1.0 </cn>
</apply>
<ci> V </ci>
<apply>
<divide/>
<ci> F </ci>
<apply>
<times/>
<ci> R </ci>
<ci> T </ci>
</apply>
</apply>
</apply>
</apply>
<apply>
<power/>
<ci> Nao </ci>
<cn cellml:units="dimensionless"> 3.0 </cn>
</apply>
<ci> Cai </ci>
</apply>
</apply>
</apply>
</apply>
</math>
</component>
<component name="calcium_buffers_in_the_myoplasm">
<variable units="micromolar" name="K_mTn" initial_value="0.5"/>
<variable units="micromolar" name="K_mCMDN" initial_value="2.38"/>
<variable units="micromolar" name="Tn_max" initial_value="70.0"/>
<variable units="micromolar" name="CMDN_max" initial_value="50.0"/>
<variable units="micromolar" name="Tn_buff"/>
<variable units="micromolar" name="CMDN_buff"/>
<variable units="millisecond" public_interface="in" name="time"/>
<variable units="micromolar" public_interface="in" name="Cai"/>
<math xmlns="http://www.w3.org/1998/Math/MathML">
<apply id="Tn_buff_calculation">
<eq/>
<ci> Tn_buff </ci>
<apply>
<times/>
<ci> Tn_max </ci>
<apply>
<divide/>
<ci> Cai </ci>
<apply>
<plus/>
<ci> Cai </ci>
<ci> K_mTn </ci>
</apply>
</apply>
</apply>
</apply>
<apply id="CMDN_buff_calculation">
<eq/>
<ci> CMDN_buff </ci>
<apply>
<times/>
<ci> CMDN_max </ci>
<apply>
<divide/>
<ci> Cai </ci>
<apply>
<plus/>
<ci> Cai </ci>
<ci> K_mCMDN </ci>
</apply>
</apply>
</apply>
</apply>
</math>
</component>
<component name="calcium_fluxes_in_the_SR">
<variable units="millimolar_per_millisecond" public_interface="out" name="i_rel"/>
<variable units="millimolar_per_millisecond" public_interface="out" name="i_up"/>
<variable units="millimolar_per_millisecond" public_interface="out" name="i_leak"/>
<variable units="millimolar_per_millisecond" public_interface="out" name="i_tr"/>
<variable units="per_millisecond" name="G_rel" initial_value="0.0"/>
<variable units="per_millisecond" name="G_rel_max" initial_value="60.0"/>
<variable units="millisecond" name="tau_on" initial_value="2.0"/>
<variable units="millisecond" name="tau_off" initial_value="2.0"/>
<variable units="millisecond" name="tau_tr" initial_value="180.0"/>
<variable units="millisecond" name="t" initial_value="0.0"/>
<variable units="micromolar" name="K_mrel" initial_value="0.8"/>
<variable units="millimolar_per_millisecond" name="delta_Ca_i"/>
<variable units="millimolar_per_millisecond" name="delta_Ca_i2"/>
<variable units="millimolar_per_millisecond" name="delta_Ca_ith"/>
<variable units="micromolar" name="K_mup" initial_value="0.92"/>
<variable units="per_millisecond" name="K_leak"/>
<variable units="millimolar_per_millisecond" name="I_up" initial_value="0.005"/>
<variable units="millimolar" name="Ca_NSR_max" initial_value="0.15"/>
<variable units="millisecond" public_interface="in" name="time"/>
<variable units="micromolar" public_interface="in" name="Cai"/>
<variable units="millimolar" public_interface="in" name="Ca_JSR"/>
<variable units="millimolar" public_interface="in" name="Ca_NSR"/>
<math xmlns="http://www.w3.org/1998/Math/MathML">
<apply id="i_rel_calculation">
<eq/>
<ci> i_rel </ci>
<apply>
<times/>
<ci> G_rel </ci>
<apply>
<minus/>
<ci> Ca_JSR </ci>
<ci> Cai </ci>
</apply>
</apply>
</apply>
<apply id="delta_Ca_i_calculation">
<eq/>
<ci> delta_Ca_i </ci>
<apply>
<times/>
<ci> delta_Ca_i2 </ci>
<cn cellml:units="dimensionless"> 1000.0 </cn>
</apply>
</apply>
<apply id="G_rel_calculation">
<eq/>
<ci> G_rel </ci>
<piecewise>
<piece>
<apply>
<times/>
<ci> G_rel_max </ci>
<apply>
<divide/>
<apply>
<minus/>
<ci> delta_Ca_i2 </ci>
<cn cellml:units="millimolar_per_millisecond"> 0.00018 </cn>
</apply>
<apply>
<minus/>
<apply>
<plus/>
<ci> K_mrel </ci>
<ci> delta_Ca_i2 </ci>
</apply>
<cn cellml:units="millimolar_per_millisecond"> 0.00018 </cn>
</apply>
</apply>
<apply>
<minus/>
<cn cellml:units="dimensionless"> 1.0 </cn>
<apply>
<exp/>
<apply>
<minus/>
<apply>
<divide/>
<ci> t </ci>
<ci> tau_on </ci>
</apply>
</apply>
</apply>
</apply>
<apply>
<exp/>
<apply>
<minus/>
<apply>
<divide/>
<ci> t </ci>
<ci> tau_off </ci>
</apply>
</apply>
</apply>
</apply>
<apply>
<gt/>
<ci> delta_Ca_i2 </ci>
<ci> delta_Ca_ith </ci>
</apply>
</piece>
<otherwise>
<apply>
<times/>
<ci> G_rel_max </ci>
<apply>
<plus/>
<apply>
<minus/>
<apply>
<times/>
<cn cellml:units="dimensionless"> 7.5 </cn>
<apply>
<power/>
<ci> delta_Ca_i </ci>
<cn cellml:units="dimensionless"> 3.0 </cn>
</apply>
</apply>
<apply>
<power/>
<ci> delta_Ca_i </ci>
<cn cellml:units="dimensionless"> 2.0 </cn>
</apply>
</apply>
<apply>
<times/>
<cn cellml:units="dimensionless"> 0.1 </cn>
<ci> delta_Ca_i </ci>
</apply>
</apply>
<apply>
<minus/>
<cn cellml:units="dimensionless"> 1.0 </cn>
<apply>
<exp/>
<apply>
<minus/>
<apply>
<divide/>
<ci> t </ci>
<ci> tau_on </ci>
</apply>
</apply>
</apply>
</apply>
<apply>
<exp/>
<apply>
<minus/>
<apply>
<divide/>
<ci> t </ci>
<ci> tau_off </ci>
</apply>
</apply>
</apply>
</apply>
</otherwise>
</piecewise>
</apply>
<apply id="i_up_calculation">
<eq/>
<ci> i_up </ci>
<apply>
<times/>
<ci> I_up </ci>
<apply>
<divide/>
<ci> Cai </ci>
<apply>
<plus/>
<ci> Cai </ci>
<ci> K_mup </ci>
</apply>
</apply>
</apply>
</apply>
<apply id="i_leak_calculation">
<eq/>
<ci> i_leak </ci>
<apply>
<times/>
<ci> K_leak </ci>
<ci> Ca_NSR </ci>
</apply>
</apply>
<apply id="K_leak_calculation">
<eq/>
<ci> K_leak </ci>
<apply>
<divide/>
<ci> I_up </ci>
<ci> Ca_NSR_max </ci>
</apply>
</apply>
<apply id="i_tr_calculation">
<eq/>
<ci> i_tr </ci>
<apply>
<divide/>
<apply>
<minus/>
<ci> Ca_NSR </ci>
<ci> Ca_JSR </ci>
</apply>
<ci> tau_tr </ci>
</apply>
</apply>
</math>
</component>
<component name="ionic_concentrations">
<variable units="millimolar" public_interface="out" name="Nai" initial_value="10.0"/>
<variable units="millimolar" public_interface="out" name="Nao" initial_value="140.0"/>
<variable units="micromolar" public_interface="out" name="Cai" initial_value="0.12"/>
<variable units="millimolar" public_interface="out" name="Cao" initial_value="1.8"/>
<variable units="millimolar" public_interface="out" name="Ki" initial_value="145.0"/>
<variable units="millimolar" public_interface="out" name="Ko" initial_value="5.4"/>
<variable units="millimolar" public_interface="out" name="Ca_JSR"/>
<variable units="millimolar" public_interface="out" name="Ca_NSR" initial_value="15.0"/>
<variable units="micromolar" name="Ca_foot"/>
<variable units="mm2" name="A_cap" initial_value="0.000153"/>
<variable units="dimensionless" name="R_A_V"/>
<variable units="micro_litre" name="V_myo"/>
<variable units="micro_litre" name="V_cleft"/>
<variable units="micro_litre" name="V_JSR"/>
<variable units="micro_litre" name="V_NSR"/>
<variable units="millisecond" public_interface="in" name="time"/>
<variable units="coulomb_per_mole" public_interface="in" name="F"/>
<variable units="microA_per_microF" public_interface="in" name="i_Na"/> <variable units="microA_per_microF" public_interface="in" name="i_CaNa"/>
<variable units="microA_per_microF" public_interface="in" name="i_Na_b"/>
<variable units="microA_per_microF" public_interface="in" name="i_ns_Na"/> <variable units="microA_per_microF" public_interface="in" name="i_NaCa"/>
<variable units="microA_per_microF" public_interface="in" name="i_NaK"/>
<variable units="microA_per_microF" public_interface="in" name="i_CaCa"/>
<variable units="microA_per_microF" public_interface="in" name="i_CaK"/>
<variable units="microA_per_microF" public_interface="in" name="i_Ca_T"/>
<variable units="microA_per_microF" public_interface="in" name="i_p_Ca"/>
<variable units="microA_per_microF" public_interface="in" name="i_Ca_b"/>
<variable units="microA_per_microF" public_interface="in" name="i_Kr"/>
<variable units="microA_per_microF" public_interface="in" name="i_Ks"/>
<variable units="microA_per_microF" public_interface="in" name="i_K1"/>
<variable units="microA_per_microF" public_interface="in" name="i_Kp"/> <variable units="microA_per_microF" public_interface="in" name="i_ns_K"/>
<variable units="microA_per_microF" public_interface="in" name="i_K_ATP"/>
<variable units="millimolar_per_millisecond" public_interface="in" name="i_tr"/>
<variable units="millimolar_per_millisecond" public_interface="in" name="i_rel"/>
<variable units="millimolar_per_millisecond" public_interface="in" name="i_leak"/>
<variable units="millimolar_per_millisecond" public_interface="in" name="i_up"/>
<math xmlns="http://www.w3.org/1998/Math/MathML">
<apply id="sodium_diff_eq">
<eq/>
<apply>
<diff/>
<bvar>
<ci> time </ci>
</bvar>
<ci> Nai </ci>
</apply>
<apply>
<times/>
<apply>
<minus/>
<apply>
<plus/>
<ci> i_Na </ci>
<ci> i_CaNa </ci>
<ci> i_Na_b </ci>
<ci> i_ns_Na </ci>
<apply>
<times/>
<ci> i_NaCa </ci>
<cn cellml:units="dimensionless"> 3.0 </cn>
</apply>
<apply>
<times/>
<ci> i_NaK </ci>
<cn cellml:units="dimensionless"> 3.0 </cn>
</apply>
</apply>
</apply>
<apply>
<divide/>
<ci> A_cap </ci>
<apply>
<times/>
<ci> V_myo </ci>
<ci> F </ci>
</apply>
</apply>
</apply>
</apply>
<apply id="calcium_internal_diff_eq">
<eq/>
<apply>
<diff/>
<bvar>
<ci> time </ci>
</bvar>
<ci> Cai </ci>
</apply>
<apply>
<plus/>
<apply>
<times/>
<apply>
<minus/>
<apply>
<plus/>
<ci> i_CaCa </ci>
<ci> i_p_Ca </ci>
<ci> i_Ca_b </ci>
<ci> i_Ca_T </ci>
</apply>
<ci> i_NaCa </ci>
</apply>
<apply>
<divide/>
<ci> A_cap </ci>
<apply>
<times/>
<cn cellml:units="dimensionless"> 2.0 </cn>
<ci> V_myo </ci>
<ci> F </ci>
</apply>
</apply>
</apply>
<apply>
<times/>
<ci> i_rel </ci>
<apply>
<divide/>
<ci> V_JSR </ci>
<ci> V_myo </ci>
</apply>
</apply>
<apply>
<times/>
<apply>
<minus/>
<ci> i_leak </ci>
<ci> i_up </ci>
</apply>
<apply>
<divide/>
<ci> V_NSR </ci>
<ci> V_myo </ci>
</apply>
</apply>
</apply>
</apply>
<apply id="potassium_internal_diff_eq">
<eq/>
<apply>
<diff/>
<bvar>
<ci> time </ci>
</bvar>
<ci> Ki </ci>
</apply>
<apply>
<times/>
<apply>
<minus/>
<apply>
<plus/>
<ci> i_CaK </ci>
<ci> i_Kr </ci>
<ci> i_Ks </ci>
<ci> i_K1 </ci>
<ci> i_K_ATP </ci>
<ci> i_Kp </ci>
<ci> i_ns_K </ci>
<apply>
<minus/>
<apply>
<times/>
<ci> i_NaK </ci>
<cn cellml:units="dimensionless"> 2.0 </cn>
</apply>
</apply>
</apply>
</apply>
<apply>
<divide/>
<ci> A_cap </ci>
<apply>
<times/>
<ci> V_myo </ci>
<ci> F </ci>
</apply>
</apply>
</apply>
</apply>
<apply id="potassium_external_diff_eq">
<eq/>
<apply>
<diff/>
<bvar>
<ci> time </ci>
</bvar>
<ci> Ko </ci>
</apply>
<apply>
<times/>
<apply>
<plus/>
<ci> i_CaK </ci>
<ci> i_Kr </ci>
<ci> i_Ks </ci>
<ci> i_K1 </ci>
<ci> i_K_ATP </ci>
<ci> i_Kp </ci>
<ci> i_ns_K </ci>
<apply>
<minus/>
<apply>
<times/>
<ci> i_NaK </ci>
<cn cellml:units="dimensionless"> 2.0 </cn>
</apply>
</apply>
</apply>
<apply>
<divide/>
<ci> A_cap </ci>
<apply>
<times/>
<ci> V_cleft </ci>
<ci> F </ci>
</apply>
</apply>
</apply>
</apply>
<apply id="calcium_JSR_diff_eq">
<eq/>
<apply>
<diff/>
<bvar>
<ci> time </ci>
</bvar>
<ci> Ca_JSR </ci>
</apply>
<apply>
<minus/>
<apply>
<minus/>
<ci> i_rel </ci>
<apply>
<times/>
<ci> i_tr </ci>
<apply>
<divide/>
<ci> V_NSR </ci>
<ci> V_JSR </ci>
</apply>
</apply>
</apply>
</apply>
</apply>
<apply id="calcium_NSR_diff_eq">
<eq/>
<apply>
<diff/>
<bvar>
<ci> time </ci>
</bvar>
<ci> Ca_NSR </ci>
</apply>
<apply>
<minus/>
<apply>
<minus/>
<apply>
<plus/>
<ci> i_leak </ci>
<ci> i_tr </ci>
</apply>
<ci> i_up </ci>
</apply>
</apply>
</apply>
<apply id="calcium_foot_diff_eq">
<eq/>
<apply>
<diff/>
<bvar>
<ci> time </ci>
</bvar>
<ci> Ca_foot </ci>
</apply>
<apply>
<times/>
<apply>
<minus/>
<ci> i_CaCa </ci>
</apply>
<apply>
<divide/>
<ci> A_cap </ci>
<apply>
<times/>
<cn cellml:units="dimensionless"> 2.0 </cn>
<ci> V_myo </ci>
<ci> F </ci>
</apply>
</apply>
<ci> R_A_V </ci>
</apply>
</apply>
</math>
</component>
<group>
<relationship_ref relationship="containment"/>
<component_ref component="membrane">
<component_ref component="transient_outward_potassium_current">
<component_ref component="transient_outward_potassium_current_z_gate"/>
<component_ref component="transient_outward_potassium_current_y_gate"/>
</component_ref>
<component_ref component="fast_sodium_current">
<component_ref component="Na_channel_states"/>
</component_ref>
<component_ref component="L_type_Ca_channel">
<component_ref component="L_type_Ca_channel_d_gate"/>
<component_ref component="L_type_Ca_channel_f_gate"/>
<component_ref component="L_type_Ca_channel_f_Ca_gate"/>
</component_ref>
<component_ref component="T_type_Ca_channel">
<component_ref component="T_type_Ca_channel_b_gate"/>
<component_ref component="T_type_Ca_channel_g_gate"/>
</component_ref>
<component_ref component="rapid_time_dependent_potassium_current">
<component_ref component="rapid_time_dependent_potassium_current_Xr_gate"/>
<component_ref component="rapid_time_dependent_potassium_current_Rr_gate"/>
</component_ref>
<component_ref component="slow_time_dependent_potassium_current">
<component_ref component="slow_time_dependent_potassium_current_Xs1_gate"/>
<component_ref component="slow_time_dependent_potassium_current_Xs2_gate"/>
</component_ref>
<component_ref component="time_independent_potassium_current">
<component_ref component="time_independent_potassium_current_K1_gate"/>
</component_ref>
<component_ref component="Na_Ca_exchanger"/>
<component_ref component="plateau_potassium_current"/>
<component_ref component="sarcolemmal_calcium_pump"/>
<component_ref component="ATP_dependent_potassium_current"/>
<component_ref component="sodium_background_current"/>
<component_ref component="calcium_background_current"/>
<component_ref component="sodium_potassium_pump"/>
<component_ref component="non_specific_calcium_activated_current"/>
<component_ref component="ionic_concentrations"/>
<component_ref component="calcium_buffers_in_the_myoplasm"/>
<component_ref component="calcium_fluxes_in_the_SR"/>
</component_ref>
</group>
<group>
<relationship_ref relationship="encapsulation"/>
<component_ref component="transient_outward_potassium_current">
<component_ref component="transient_outward_potassium_current_z_gate"/>
<component_ref component="transient_outward_potassium_current_y_gate"/>
</component_ref>
<component_ref component="fast_sodium_current">
<component_ref component="Na_channel_states"/>
</component_ref>
<component_ref component="L_type_Ca_channel">
<component_ref component="L_type_Ca_channel_d_gate"/>
<component_ref component="L_type_Ca_channel_f_gate"/>
<component_ref component="L_type_Ca_channel_f_Ca_gate"/>
</component_ref>
<component_ref component="T_type_Ca_channel">
<component_ref component="T_type_Ca_channel_b_gate"/>
<component_ref component="T_type_Ca_channel_g_gate"/>
</component_ref>
<component_ref component="rapid_time_dependent_potassium_current">
<component_ref component="rapid_time_dependent_potassium_current_Xr_gate"/>
<component_ref component="rapid_time_dependent_potassium_current_Rr_gate"/>
</component_ref>
<component_ref component="slow_time_dependent_potassium_current">
<component_ref component="slow_time_dependent_potassium_current_Xs1_gate"/>
<component_ref component="slow_time_dependent_potassium_current_Xs2_gate"/>
</component_ref>
<component_ref component="time_independent_potassium_current">
<component_ref component="time_independent_potassium_current_K1_gate"/>
</component_ref>
</group>
<connection>
<map_components component_2="environment" component_1="membrane"/>
<map_variables variable_2="time" variable_1="time"/>
</connection>
<connection>
<map_components component_2="environment" component_1="fast_sodium_current"/>
<map_variables variable_2="time" variable_1="time"/>
</connection>
<connection>
<map_components component_2="environment" component_1="L_type_Ca_channel"/>
<map_variables variable_2="time" variable_1="time"/>
</connection>
<connection>
<map_components component_2="environment" component_1="T_type_Ca_channel"/>
<map_variables variable_2="time" variable_1="time"/>
</connection>
<connection>
<map_components component_2="environment" component_1="rapid_time_dependent_potassium_current"/>
<map_variables variable_2="time" variable_1="time"/>
</connection>
<connection>
<map_components component_2="environment" component_1="slow_time_dependent_potassium_current"/>
<map_variables variable_2="time" variable_1="time"/>
</connection>
<connection>
<map_components component_2="environment" component_1="time_independent_potassium_current"/>
<map_variables variable_2="time" variable_1="time"/>
</connection>
<connection>
<map_components component_2="environment" component_1="ATP_dependent_potassium_current"/>
<map_variables variable_2="time" variable_1="time"/>
</connection>
<connection>
<map_components component_2="environment" component_1="Na_Ca_exchanger"/>
<map_variables variable_2="time" variable_1="time"/>
</connection>
<connection>
<map_components component_2="environment" component_1="plateau_potassium_current"/>
<map_variables variable_2="time" variable_1="time"/>
</connection>
<connection>
<map_components component_2="environment" component_1="sarcolemmal_calcium_pump"/>
<map_variables variable_2="time" variable_1="time"/>
</connection>
<connection>
<map_components component_2="environment" component_1="sodium_background_current"/>
<map_variables variable_2="time" variable_1="time"/>
</connection>
<connection>
<map_components component_2="environment" component_1="calcium_background_current"/>
<map_variables variable_2="time" variable_1="time"/>
</connection>
<connection>
<map_components component_2="environment" component_1="sodium_potassium_pump"/>
<map_variables variable_2="time" variable_1="time"/>
</connection>
<connection>
<map_components component_2="environment" component_1="transient_outward_potassium_current"/>
<map_variables variable_2="time" variable_1="time"/>
</connection>
<connection>
<map_components component_2="environment" component_1="non_specific_calcium_activated_current"/>
<map_variables variable_2="time" variable_1="time"/>
</connection>
<connection>
<map_components component_2="environment" component_1="ionic_concentrations"/>
<map_variables variable_2="time" variable_1="time"/>
</connection>
<connection>
<map_components component_2="environment" component_1="calcium_buffers_in_the_myoplasm"/>
<map_variables variable_2="time" variable_1="time"/>
</connection>
<connection>
<map_components component_2="environment" component_1="calcium_fluxes_in_the_SR"/>
<map_variables variable_2="time" variable_1="time"/>
</connection>
<connection>
<map_components component_2="transient_outward_potassium_current" component_1="membrane"/>
<map_variables variable_2="V" variable_1="V"/>
<map_variables variable_2="i_to" variable_1="i_to"/>
</connection>
<connection>
<map_components component_2="fast_sodium_current" component_1="membrane"/>
<map_variables variable_2="V" variable_1="V"/>
<map_variables variable_2="i_Na" variable_1="i_Na"/>
<map_variables variable_2="R" variable_1="R"/>
<map_variables variable_2="T" variable_1="T"/>
<map_variables variable_2="F" variable_1="F"/>
</connection>
<connection>
<map_components component_2="L_type_Ca_channel" component_1="membrane"/>
<map_variables variable_2="V" variable_1="V"/>
<map_variables variable_2="i_Ca_L" variable_1="i_Ca_L"/>
<map_variables variable_2="R" variable_1="R"/>
<map_variables variable_2="T" variable_1="T"/>
<map_variables variable_2="F" variable_1="F"/>
</connection>
<connection>
<map_components component_2="T_type_Ca_channel" component_1="membrane"/>
<map_variables variable_2="V" variable_1="V"/>
<map_variables variable_2="i_Ca_T" variable_1="i_Ca_T"/>
<map_variables variable_2="R" variable_1="R"/>
<map_variables variable_2="T" variable_1="T"/>
<map_variables variable_2="F" variable_1="F"/>
</connection>
<connection>
<map_components component_2="rapid_time_dependent_potassium_current" component_1="membrane"/>
<map_variables variable_2="V" variable_1="V"/>
<map_variables variable_2="i_Kr" variable_1="i_Kr"/>
<map_variables variable_2="R" variable_1="R"/>
<map_variables variable_2="T" variable_1="T"/>
<map_variables variable_2="F" variable_1="F"/>
</connection>
<connection>
<map_components component_2="slow_time_dependent_potassium_current" component_1="membrane"/>
<map_variables variable_2="V" variable_1="V"/>
<map_variables variable_2="i_Ks" variable_1="i_Ks"/>
<map_variables variable_2="R" variable_1="R"/>
<map_variables variable_2="T" variable_1="T"/>
<map_variables variable_2="F" variable_1="F"/>
</connection>
<connection>
<map_components component_2="Na_Ca_exchanger" component_1="membrane"/>
<map_variables variable_2="V" variable_1="V"/>
<map_variables variable_2="i_NaCa" variable_1="i_NaCa"/>
<map_variables variable_2="R" variable_1="R"/>
<map_variables variable_2="T" variable_1="T"/>
<map_variables variable_2="F" variable_1="F"/>
</connection>
<connection>
<map_components component_2="ATP_dependent_potassium_current" component_1="membrane"/>
<map_variables variable_2="V" variable_1="V"/>
<map_variables variable_2="i_K_ATP" variable_1="i_K_ATP"/>
<map_variables variable_2="R" variable_1="R"/>
<map_variables variable_2="T" variable_1="T"/>
<map_variables variable_2="F" variable_1="F"/>
</connection>
<connection>
<map_components component_2="time_independent_potassium_current" component_1="membrane"/>
<map_variables variable_2="V" variable_1="V"/>
<map_variables variable_2="i_K1" variable_1="i_K1"/>
<map_variables variable_2="R" variable_1="R"/>
<map_variables variable_2="T" variable_1="T"/>
<map_variables variable_2="F" variable_1="F"/>
</connection>
<connection>
<map_components component_2="plateau_potassium_current" component_1="membrane"/>
<map_variables variable_2="V" variable_1="V"/>
<map_variables variable_2="i_Kp" variable_1="i_Kp"/>
</connection>
<connection>
<map_components component_2="sarcolemmal_calcium_pump" component_1="membrane"/>
<map_variables variable_2="i_p_Ca" variable_1="i_p_Ca"/>
</connection>
<connection>
<map_components component_2="sodium_background_current" component_1="membrane"/>
<map_variables variable_2="V" variable_1="V"/>
<map_variables variable_2="i_Na_b" variable_1="i_Na_b"/>
</connection>
<connection>
<map_components component_2="calcium_background_current" component_1="membrane"/>
<map_variables variable_2="V" variable_1="V"/>
<map_variables variable_2="i_Ca_b" variable_1="i_Ca_b"/>
<map_variables variable_2="R" variable_1="R"/>
<map_variables variable_2="T" variable_1="T"/>
<map_variables variable_2="F" variable_1="F"/>
</connection>
<connection>
<map_components component_2="sodium_potassium_pump" component_1="membrane"/>
<map_variables variable_2="V" variable_1="V"/>
<map_variables variable_2="i_NaK" variable_1="i_NaK"/>
<map_variables variable_2="R" variable_1="R"/>
<map_variables variable_2="T" variable_1="T"/>
<map_variables variable_2="F" variable_1="F"/>
</connection>
<connection>
<map_components component_2="non_specific_calcium_activated_current" component_1="membrane"/>
<map_variables variable_2="V" variable_1="V"/>
<map_variables variable_2="R" variable_1="R"/>
<map_variables variable_2="T" variable_1="T"/>
<map_variables variable_2="F" variable_1="F"/>
<map_variables variable_2="i_ns_Ca" variable_1="i_ns_Ca"/>
</connection>
<connection>
<map_components component_2="ionic_concentrations" component_1="membrane"/>
<map_variables variable_2="F" variable_1="F"/>
</connection>
<connection>
<map_components component_2="ionic_concentrations" component_1="fast_sodium_current"/>
<map_variables variable_2="i_Na" variable_1="i_Na"/>
<map_variables variable_2="Nao" variable_1="Nao"/>
<map_variables variable_2="Nai" variable_1="Nai"/>
</connection>
<connection>
<map_components component_2="sodium_background_current" component_1="fast_sodium_current"/>
<map_variables variable_2="E_Na" variable_1="E_Na"/>
</connection>
<connection>
<map_components component_2="transient_outward_potassium_current" component_1="ATP_dependent_potassium_current"/>
<map_variables variable_2="E_K" variable_1="E_K"/>
</connection>
<connection>
<map_components component_2="ionic_concentrations" component_1="L_type_Ca_channel"/>
<map_variables variable_2="Cai" variable_1="Cai"/>
<map_variables variable_2="Cao" variable_1="Cao"/>
<map_variables variable_2="Nao" variable_1="Nao"/>
<map_variables variable_2="Nai" variable_1="Nai"/>
<map_variables variable_2="Ko" variable_1="Ko"/>
<map_variables variable_2="Ki" variable_1="Ki"/>
<map_variables variable_2="i_CaCa" variable_1="i_CaCa"/>
<map_variables variable_2="i_CaNa" variable_1="i_CaNa"/>
<map_variables variable_2="i_CaK" variable_1="i_CaK"/>
</connection>
<connection>
<map_components component_2="ionic_concentrations" component_1="T_type_Ca_channel"/>
<map_variables variable_2="Cai" variable_1="Cai"/>
<map_variables variable_2="Cao" variable_1="Cao"/>
<map_variables variable_2="i_Ca_T" variable_1="i_Ca_T"/>
</connection>
<connection>
<map_components component_2="ionic_concentrations" component_1="rapid_time_dependent_potassium_current"/>
<map_variables variable_2="Ki" variable_1="Ki"/>
<map_variables variable_2="Ko" variable_1="Ko"/>
<map_variables variable_2="i_Kr" variable_1="i_Kr"/>
</connection>
<connection>
<map_components component_2="ionic_concentrations" component_1="slow_time_dependent_potassium_current"/>
<map_variables variable_2="Ki" variable_1="Ki"/>
<map_variables variable_2="Ko" variable_1="Ko"/>
<map_variables variable_2="Nai" variable_1="Nai"/>
<map_variables variable_2="Nao" variable_1="Nao"/>
<map_variables variable_2="Cai" variable_1="Cai"/>
<map_variables variable_2="i_Ks" variable_1="i_Ks"/>
</connection>
<connection>
<map_components component_2="ionic_concentrations" component_1="ATP_dependent_potassium_current"/>
<map_variables variable_2="Ki" variable_1="Ki"/>
<map_variables variable_2="Ko" variable_1="Ko"/>
<map_variables variable_2="i_K_ATP" variable_1="i_K_ATP"/>
</connection>
<connection>
<map_components component_2="ionic_concentrations" component_1="Na_Ca_exchanger"/>
<map_variables variable_2="Cai" variable_1="Cai"/>
<map_variables variable_2="Nai" variable_1="Nai"/>
<map_variables variable_2="Cao" variable_1="Cao"/>
<map_variables variable_2="Nao" variable_1="Nao"/>
<map_variables variable_2="i_NaCa" variable_1="i_NaCa"/>
</connection>
<connection>
<map_components component_2="ionic_concentrations" component_1="time_independent_potassium_current"/>
<map_variables variable_2="Ki" variable_1="Ki"/>
<map_variables variable_2="Ko" variable_1="Ko"/>
<map_variables variable_2="i_K1" variable_1="i_K1"/>
</connection>
<connection>
<map_components component_2="time_independent_potassium_current" component_1="plateau_potassium_current"/>
<map_variables variable_2="E_K1" variable_1="E_K1"/>
</connection>
<connection>
<map_components component_2="ionic_concentrations" component_1="plateau_potassium_current"/>
<map_variables variable_2="i_Kp" variable_1="i_Kp"/>
</connection>
<connection>
<map_components component_2="ionic_concentrations" component_1="sarcolemmal_calcium_pump"/>
<map_variables variable_2="i_p_Ca" variable_1="i_p_Ca"/>
<map_variables variable_2="Cai" variable_1="Cai"/>
</connection>
<connection>
<map_components component_2="ionic_concentrations" component_1="sodium_background_current"/>
<map_variables variable_2="i_Na_b" variable_1="i_Na_b"/>
</connection>
<connection>
<map_components component_2="ionic_concentrations" component_1="calcium_background_current"/>
<map_variables variable_2="Cai" variable_1="Cai"/>
<map_variables variable_2="Cao" variable_1="Cao"/>
<map_variables variable_2="i_Ca_b" variable_1="i_Ca_b"/>
</connection>
<connection>
<map_components component_2="ionic_concentrations" component_1="sodium_potassium_pump"/>
<map_variables variable_2="Nai" variable_1="Nai"/>
<map_variables variable_2="Nao" variable_1="Nao"/>
<map_variables variable_2="Ko" variable_1="Ko"/>
<map_variables variable_2="i_NaK" variable_1="i_NaK"/>
</connection>
<connection>
<map_components component_2="ionic_concentrations" component_1="non_specific_calcium_activated_current"/>
<map_variables variable_2="Cai" variable_1="Cai"/>
<map_variables variable_2="Cao" variable_1="Cao"/>
<map_variables variable_2="Nao" variable_1="Nao"/>
<map_variables variable_2="Nai" variable_1="Nai"/>
<map_variables variable_2="Ko" variable_1="Ko"/>
<map_variables variable_2="Ki" variable_1="Ki"/>
<map_variables variable_2="i_ns_Na" variable_1="i_ns_Na"/>
<map_variables variable_2="i_ns_K" variable_1="i_ns_K"/>
</connection>
<connection>
<map_components component_2="non_specific_calcium_activated_current" component_1="L_type_Ca_channel"/>
<map_variables variable_2="gamma_Nao" variable_1="gamma_Nao"/>
<map_variables variable_2="gamma_Nai" variable_1="gamma_Nai"/>
<map_variables variable_2="gamma_Ko" variable_1="gamma_Ko"/>
<map_variables variable_2="gamma_Ki" variable_1="gamma_Ki"/>
</connection>
<connection>
<map_components component_2="ionic_concentrations" component_1="calcium_buffers_in_the_myoplasm"/>
<map_variables variable_2="Cai" variable_1="Cai"/>
</connection>
<connection>
<map_components component_2="ionic_concentrations" component_1="calcium_fluxes_in_the_SR"/>
<map_variables variable_2="i_rel" variable_1="i_rel"/>
<map_variables variable_2="i_tr" variable_1="i_tr"/>
<map_variables variable_2="i_leak" variable_1="i_leak"/>
<map_variables variable_2="i_up" variable_1="i_up"/>
<map_variables variable_2="Cai" variable_1="Cai"/>
<map_variables variable_2="Ca_JSR" variable_1="Ca_JSR"/>
<map_variables variable_2="Ca_NSR" variable_1="Ca_NSR"/>
</connection>
<connection>
<map_components component_2="transient_outward_potassium_current_z_gate" component_1="transient_outward_potassium_current"/>
<map_variables variable_2="z" variable_1="z"/>
<map_variables variable_2="time" variable_1="time"/>
<map_variables variable_2="V" variable_1="V"/>
</connection>
<connection>
<map_components component_2="transient_outward_potassium_current_y_gate" component_1="transient_outward_potassium_current"/>
<map_variables variable_2="y" variable_1="y"/>
<map_variables variable_2="time" variable_1="time"/>
<map_variables variable_2="V" variable_1="V"/>
</connection>
<connection>
<map_components component_2="Na_channel_states" component_1="fast_sodium_current"/>
<map_variables variable_2="P_O_Na" variable_1="P_O_Na"/>
<map_variables variable_2="time" variable_1="time"/>
<map_variables variable_2="V" variable_1="V"/>
</connection>
<connection>
<map_components component_2="L_type_Ca_channel_d_gate" component_1="L_type_Ca_channel"/>
<map_variables variable_2="d" variable_1="d"/>
<map_variables variable_2="time" variable_1="time"/>
<map_variables variable_2="V" variable_1="V"/>
</connection>
<connection>
<map_components component_2="L_type_Ca_channel_f_gate" component_1="L_type_Ca_channel"/>
<map_variables variable_2="f" variable_1="f"/>
<map_variables variable_2="time" variable_1="time"/>
<map_variables variable_2="V" variable_1="V"/>
</connection>
<connection>
<map_components component_2="L_type_Ca_channel_f_Ca_gate" component_1="L_type_Ca_channel"/>
<map_variables variable_2="f_Ca" variable_1="f_Ca"/>
<map_variables variable_2="time" variable_1="time"/>
<map_variables variable_2="Cai" variable_1="Cai"/>
<map_variables variable_2="V" variable_1="V"/>
</connection>
<connection>
<map_components component_2="T_type_Ca_channel_b_gate" component_1="T_type_Ca_channel"/>
<map_variables variable_2="b" variable_1="b"/>
<map_variables variable_2="time" variable_1="time"/>
<map_variables variable_2="V" variable_1="V"/>
</connection>
<connection>
<map_components component_2="T_type_Ca_channel_g_gate" component_1="T_type_Ca_channel"/>
<map_variables variable_2="g" variable_1="g"/>
<map_variables variable_2="time" variable_1="time"/>
<map_variables variable_2="V" variable_1="V"/>
</connection>
<connection>
<map_components component_2="rapid_time_dependent_potassium_current_Xr_gate" component_1="rapid_time_dependent_potassium_current"/>
<map_variables variable_2="Xr" variable_1="Xr"/>
<map_variables variable_2="time" variable_1="time"/>
<map_variables variable_2="V" variable_1="V"/>
</connection>
<connection>
<map_components component_2="rapid_time_dependent_potassium_current_Rr_gate" component_1="rapid_time_dependent_potassium_current"/>
<map_variables variable_2="Rr" variable_1="Rr"/>
<map_variables variable_2="time" variable_1="time"/>
<map_variables variable_2="V" variable_1="V"/>
</connection>
<connection>
<map_components component_2="slow_time_dependent_potassium_current_Xs1_gate" component_1="slow_time_dependent_potassium_current"/>
<map_variables variable_2="Xs1" variable_1="Xs1"/>
<map_variables variable_2="time" variable_1="time"/>
<map_variables variable_2="V" variable_1="V"/>
</connection>
<connection>
<map_components component_2="slow_time_dependent_potassium_current_Xs2_gate" component_1="slow_time_dependent_potassium_current"/>
<map_variables variable_2="Xs2" variable_1="Xs2"/>
<map_variables variable_2="time" variable_1="time"/>
<map_variables variable_2="V" variable_1="V"/>
</connection>
<connection>
<map_components component_2="slow_time_dependent_potassium_current_Xs2_gate" component_1="slow_time_dependent_potassium_current_Xs1_gate"/>
<map_variables variable_2="tau_Xs1" variable_1="tau_Xs1"/>
<map_variables variable_2="Xs_infinity" variable_1="Xs_infinity"/>
</connection>
<connection>
<map_components component_2="time_independent_potassium_current_K1_gate" component_1="time_independent_potassium_current"/>
<map_variables variable_2="K1_infinity" variable_1="K1_infinity"/>
<map_variables variable_2="E_K1" variable_1="E_K1"/>
<map_variables variable_2="time" variable_1="time"/>
<map_variables variable_2="V" variable_1="V"/>
</connection>
<rdf:RDF>
<rdf:Bag rdf:about="rdf:#9a2484a4-5347-4c2a-ae56-1ba2ecf92d03">
<rdf:li>cardiac</rdf:li>
<rdf:li>Brugada Syndrome</rdf:li>
<rdf:li>Long QT Syndrome</rdf:li>
<rdf:li>electrophysiology</rdf:li>
<rdf:li>na channel</rdf:li>
</rdf:Bag>
<rdf:Seq rdf:about="rdf:#b962ed3b-3bf1-42c2-abc2-1f84f04fb6ea">
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</rdf:Seq>
<rdf:Description rdf:about="">
<dc:publisher>The University of Auckland, The Bioengineering Institute</dc:publisher>
<cmeta:comment rdf:resource="rdf:#429d3bf8-0794-4a0c-b7a5-6d166003caad"/>
<dcterms:created rdf:resource="rdf:#b117ebec-647a-46a3-9edd-e49c3395f906"/>
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<rdf:Description rdf:about="rdf:#d803aa7b-3f78-413b-9645-1513adc20163">
<vCard:Orgname>The University of Auckland</vCard:Orgname>
<vCard:Orgunit>The Bioengineering Institute</vCard:Orgunit>
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<rdf:Description rdf:about="rdf:#a1af5d01-f40f-466a-815e-306d5f32c684">
<dcterms:modified rdf:resource="rdf:#38ab0814-528a-468a-a1a1-e3135f1e5378"/>
<rdf:value>updated curation status,
removed publication link in documentation</rdf:value>
<cmeta:modifier rdf:resource="rdf:#0a232fa0-1166-4841-9e92-e410fd7aa7e3"/>
</rdf:Description>
<rdf:Description rdf:about="rdf:#3d57aa7e-c598-40f4-af54-f697ee73a61a">
<vCard:FN>James Lawson</vCard:FN>
</rdf:Description>
<rdf:Description rdf:about="rdf:#0e44e421-22d5-49a9-b0dc-318da090e7f5">
<dcterms:W3CDTF>2007-08-16T12:26:07+12:00</dcterms:W3CDTF>
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<rdf:value>This model is currently unable to be supported due to its dependence on the Luo Rudy 1994 model, which contains delay elements in its model of the CIRC, which can not yet be represented in CellML (as of CellML 1.1). Therefore this model is unconstrained and does not load or run in any simulator.</rdf:value>
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<vCard:Given>Colleen</vCard:Given>
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<vCard:Other>E</vCard:Other>
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<vCard:FN>Catherine Lloyd</vCard:FN>
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<rdf:value>Added value of 1.5e-2 to variable I_NaK (note, not i_NaK) in component "sodium_potassium_pump". This value was obtained from the LR94 dynamic model</rdf:value>
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<vCard:Given>Catherine</vCard:Given>
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<dc:title>Circulation</dc:title>
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<bqs:Pubmed_id>11889015</bqs:Pubmed_id>
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<dcterms:W3CDTF>2002-03-12</dcterms:W3CDTF>
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<vCard:Given>James</vCard:Given>
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<vCard:Other>Richard</vCard:Other>
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<vCard:Given>Yoram</vCard:Given>
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<dc:title>The Clancy and Rudy's 2002 mathematical model of a Na channel mutation that causes both Brugada and long-QT syndrome phenotypes.</dc:title>
<cmeta:bio_entity>Ventricular Myocyte</cmeta:bio_entity>
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<cmeta:species>Mammalia</cmeta:species>
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<dc:title>Na Channel Mutation That Causes Both Brugada Syndrome and Long-QT Syndrome Phenotypes: A Simulation Study of Mechanism</dc:title>
<bqs:volume>105</bqs:volume>
<bqs:first_page>1208</bqs:first_page>
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