- Author:
- pmr2.import <nobody@models.cellml.org>
- Date:
- 2006-09-14 23:32:29+12:00
- Desc:
- committing version03 of noble_varghese_kohl_noble_1998
- Permanent Source URI:
- https://staging.physiomeproject.org/workspace/noble_varghese_kohl_noble_1998/rawfile/a56299a5856ec03349e3618d0da1c156e151ebfe/noble_varghese_kohl_noble_1998.cellml
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<!--
This CellML file was generated on 17/08/2005 at 15:50:01 using:
COR (0.9.31.83)
Copyright 2002-2005 Oxford Cardiac Electrophysiology Group
http://COR.physiol.ox.ac.uk/ - COR@physiol.ox.ac.uk
CellML 1.0 was used to generate this cellular model
http://www.CellML.org/
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<documentation xmlns="http://cellml.org/tmp-documentation">
<article>
<articleinfo>
<title>Noble Ventricular Cell Model 1998</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 is the original unchecked version of the model imported from the previous
CellML model repository, 24-Jan-2006.
</para>
</section>
<sect1 id="sec_structure">
<title>Model Structure</title>
<para>In their 1998 paper, Denis Noble, Anthony Varghese, Peter Kohl and Penny Noble extended the guinea-pig ventricular cell model (originally developed in 1991 by Noble <emphasis>et al</emphasis>) to include accumulation and depletion of calcium in a diadic space between the sarcolemma and the sarcoplasmic reticulum, where the majority of calcium-induced calcium release is triggered. The model also includes rapid (i_Kr) and slow (i_Ks) components of the delayed rectifier current, and length- and tension-dependent changes in mechanical and electrophysiological processes have been incorporated (see <xref linkend="fig_cell_diagram"/> below). Drug-receptor interactions have also started to be modeled using the sodium channel as an example. The drugs used have the effect of blocking the inactivation h-gate of the fast sodium channel.
</para>
<para>
The complete original paper reference is cited below:
</para>
<para>
<ulink url="http://www.pulsus.com/CARDIOL/14_01/nobl_ed.htm">Improved guinea-pig ventricular cell model incorporating a diadic space, I<subscript>Kr</subscript> and I<subscript>Ks</subscript>, and length- and tension-dependent processes</ulink>, Denis Noble, Anthony Varghese, Peter Kohl and Penelope Noble, 1998, <ulink url="http://www.pulsus.com/CARDIOL/home.htm">
<emphasis>Can J Cardiol</emphasis>
</ulink>, 14, 123-134. <ulink url="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=9487284&dopt=Abstract">PubMed ID: 9487284</ulink>
</para>
<para>
The raw CellML description of the Noble'98 model can be downloaded in various formats as described in <xref linkend="sec_download_this_model"/>. For an example of a more complete documentation for an electrophysiological model, see <ulink url="${HTML_EXMPL_HHSA_INTRO}">The Hodgkin-Huxley Squid Axon Model, 1952</ulink>.
</para>
<informalfigure float="0" id="fig_cell_diagram">
<mediaobject>
<imageobject>
<objectinfo>
<title>cell diagram of Noble'98 model showing ionic currents, pumps and exchangers within the sarcolemma and the sarcoplasmic reticulum</title>
</objectinfo>
<imagedata fileref="noble_1998.png"/>
</imageobject>
</mediaobject>
<caption>A schematic diagram describing the current flows across the cell membrane that are captured in the Noble'98 model.</caption>
</informalfigure>
</sect1>
</article>
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<plus/>
<cn cellml:units="dimensionless">1</cn>
<apply>
<exp/>
<apply>
<divide/>
<apply>
<minus/>
<apply>
<minus/>
<ci>V</ci>
<cn cellml:units="millivolt">40</cn>
</apply>
</apply>
<cn cellml:units="millivolt">9</cn>
</apply>
</apply>
</apply>
</apply>
</apply>
<apply>
<eq/>
<ci>beta_xs</ci>
<apply>
<times/>
<cn cellml:units="per_second">1</cn>
<apply>
<exp/>
<apply>
<divide/>
<apply>
<minus/>
<ci>V</ci>
</apply>
<cn cellml:units="millivolt">45</cn>
</apply>
</apply>
</apply>
</apply>
<apply>
<eq/>
<apply>
<diff/>
<bvar>
<ci>time</ci>
</bvar>
<ci>xs</ci>
</apply>
<apply>
<minus/>
<apply>
<times/>
<ci>alpha_xs</ci>
<apply>
<minus/>
<cn cellml:units="dimensionless">1</cn>
<ci>xs</ci>
</apply>
</apply>
<apply>
<times/>
<ci>beta_xs</ci>
<ci>xs</ci>
</apply>
</apply>
</apply>
</math>
</component>
<component name="fast_sodium_current">
<variable units="nanoamp" public_interface="out" name="i_Na"/>
<variable units="microS" name="g_Na" initial_value="2.5"/>
<variable units="millivolt" public_interface="in" name="E_mh"/>
<variable units="second" public_interface="in" private_interface="out" name="time"/>
<variable units="millivolt" public_interface="in" private_interface="out" name="V"/>
<variable units="dimensionless" private_interface="in" name="m"/>
<variable units="dimensionless" private_interface="in" name="h"/>
<math xmlns="http://www.w3.org/1998/Math/MathML">
<apply>
<eq/>
<ci>i_Na</ci>
<apply>
<times/>
<ci>g_Na</ci>
<apply>
<power/>
<ci>m</ci>
<cn cellml:units="dimensionless">3</cn>
</apply>
<ci>h</ci>
<apply>
<minus/>
<ci>V</ci>
<ci>E_mh</ci>
</apply>
</apply>
</apply>
</math>
</component>
<component name="fast_sodium_current_m_gate">
<variable units="dimensionless" public_interface="out" name="m" initial_value="0.0016203"/>
<variable units="per_second" name="alpha_m"/>
<variable units="per_second" name="beta_m"/>
<variable units="millivolt" public_interface="in" name="V"/>
<variable units="second" public_interface="in" name="time"/>
<variable units="dimensionless" name="delta_m" initial_value="1e-5"/>
<variable units="millivolt" name="E0_m"/>
<math xmlns="http://www.w3.org/1998/Math/MathML">
<apply>
<eq/>
<ci>E0_m</ci>
<apply>
<plus/>
<ci>V</ci>
<cn cellml:units="millivolt">41</cn>
</apply>
</apply>
<apply>
<eq/>
<ci>alpha_m</ci>
<piecewise>
<piece>
<cn cellml:units="per_second">2000</cn>
<apply>
<lt/>
<apply>
<abs/>
<ci>E0_m</ci>
</apply>
<apply>
<times/>
<ci>delta_m</ci>
<cn cellml:units="millivolt">1</cn>
</apply>
</apply>
</piece>
<otherwise>
<apply>
<divide/>
<apply>
<times/>
<cn cellml:units="per_millivolt_second">200</cn>
<ci>E0_m</ci>
</apply>
<apply>
<minus/>
<cn cellml:units="dimensionless">1</cn>
<apply>
<exp/>
<apply>
<times/>
<apply>
<minus/>
<cn cellml:units="per_millivolt">0.1</cn>
</apply>
<ci>E0_m</ci>
</apply>
</apply>
</apply>
</apply>
</otherwise>
</piecewise>
</apply>
<apply>
<eq/>
<ci>beta_m</ci>
<apply>
<times/>
<cn cellml:units="per_second">8000</cn>
<apply>
<exp/>
<apply>
<times/>
<apply>
<minus/>
<cn cellml:units="per_millivolt">0.056</cn>
</apply>
<apply>
<plus/>
<ci>V</ci>
<cn cellml:units="millivolt">66</cn>
</apply>
</apply>
</apply>
</apply>
</apply>
<apply>
<eq/>
<apply>
<diff/>
<bvar>
<ci>time</ci>
</bvar>
<ci>m</ci>
</apply>
<apply>
<minus/>
<apply>
<times/>
<ci>alpha_m</ci>
<apply>
<minus/>
<cn cellml:units="dimensionless">1</cn>
<ci>m</ci>
</apply>
</apply>
<apply>
<times/>
<ci>beta_m</ci>
<ci>m</ci>
</apply>
</apply>
</apply>
</math>
</component>
<component name="fast_sodium_current_h_gate">
<variable units="dimensionless" public_interface="out" name="h" initial_value="0.9944036"/>
<variable units="per_second" name="alpha_h"/>
<variable units="per_second" name="beta_h"/>
<variable units="millivolt" public_interface="in" name="V"/>
<variable units="second" public_interface="in" name="time"/>
<math xmlns="http://www.w3.org/1998/Math/MathML">
<apply>
<eq/>
<ci>alpha_h</ci>
<apply>
<times/>
<cn cellml:units="per_second">20</cn>
<apply>
<exp/>
<apply>
<times/>
<apply>
<minus/>
<cn cellml:units="per_millivolt">0.125</cn>
</apply>
<apply>
<plus/>
<ci>V</ci>
<cn cellml:units="millivolt">75</cn>
</apply>
</apply>
</apply>
</apply>
</apply>
<apply>
<eq/>
<ci>beta_h</ci>
<apply>
<divide/>
<cn cellml:units="per_second">2000</cn>
<apply>
<plus/>
<cn cellml:units="dimensionless">1</cn>
<apply>
<times/>
<cn cellml:units="dimensionless">320</cn>
<apply>
<exp/>
<apply>
<times/>
<apply>
<minus/>
<cn cellml:units="per_millivolt">0.1</cn>
</apply>
<apply>
<plus/>
<ci>V</ci>
<cn cellml:units="millivolt">75</cn>
</apply>
</apply>
</apply>
</apply>
</apply>
</apply>
</apply>
<apply>
<eq/>
<apply>
<diff/>
<bvar>
<ci>time</ci>
</bvar>
<ci>h</ci>
</apply>
<apply>
<minus/>
<apply>
<times/>
<ci>alpha_h</ci>
<apply>
<minus/>
<cn cellml:units="dimensionless">1</cn>
<ci>h</ci>
</apply>
</apply>
<apply>
<times/>
<ci>beta_h</ci>
<ci>h</ci>
</apply>
</apply>
</apply>
</math>
</component>
<component name="persistent_sodium_current">
<variable units="nanoamp" public_interface="out" name="i_p_Na"/>
<variable units="microS" name="g_pna" initial_value="0.004"/>
<variable units="millivolt" public_interface="in" name="E_Na"/>
<variable units="second" public_interface="in" name="time"/>
<variable units="millivolt" public_interface="in" name="V"/>
<math xmlns="http://www.w3.org/1998/Math/MathML">
<apply>
<eq/>
<ci>i_p_Na</ci>
<apply>
<times/>
<apply>
<divide/>
<apply>
<times/>
<ci>g_pna</ci>
<cn cellml:units="dimensionless">1</cn>
</apply>
<apply>
<plus/>
<cn cellml:units="dimensionless">1</cn>
<apply>
<exp/>
<apply>
<divide/>
<apply>
<minus/>
<apply>
<plus/>
<ci>V</ci>
<cn cellml:units="millivolt">52</cn>
</apply>
</apply>
<cn cellml:units="millivolt">8</cn>
</apply>
</apply>
</apply>
</apply>
<apply>
<minus/>
<ci>V</ci>
<ci>E_Na</ci>
</apply>
</apply>
</apply>
</math>
</component>
<component name="sodium_background_current">
<variable units="nanoamp" public_interface="out" name="i_b_Na"/>
<variable units="microS" name="g_bna" initial_value="0.0006"/>
<variable units="millimolar" public_interface="in" name="Na_i"/>
<variable units="millivolt" public_interface="in" name="E_Na"/>
<variable units="second" public_interface="in" name="time"/>
<variable units="millivolt" public_interface="in" name="V"/>
<math xmlns="http://www.w3.org/1998/Math/MathML">
<apply>
<eq/>
<ci>i_b_Na</ci>
<apply>
<times/>
<ci>g_bna</ci>
<apply>
<minus/>
<ci>V</ci>
<ci>E_Na</ci>
</apply>
</apply>
</apply>
</math>
</component>
<component name="L_type_Ca_channel">
<variable units="nanoamp" public_interface="out" name="i_Ca_L_Ca_cyt"/>
<variable units="nanoamp" public_interface="out" name="i_Ca_L_K_cyt"/>
<variable units="nanoamp" public_interface="out" name="i_Ca_L_Na_cyt"/>
<variable units="nanoamp" public_interface="out" name="i_Ca_L_Ca_ds"/>
<variable units="nanoamp" public_interface="out" name="i_Ca_L_K_ds"/>
<variable units="nanoamp" public_interface="out" name="i_Ca_L_Na_ds"/>
<variable units="nanoamp" public_interface="out" name="i_Ca_L"/>
<variable units="nanoamp_per_millimolar" name="P_Ca_L" initial_value="0.1"/>
<variable units="nanoamp_per_millimolar" name="P_CaK" initial_value="0.002"/>
<variable units="nanoamp_per_millimolar" name="P_CaNa" initial_value="0.01"/>
<variable units="millimolar" public_interface="in" name="Ca_o"/>
<variable units="millimolar" public_interface="in" private_interface="out" name="Ca_i"/>
<variable units="millimolar" public_interface="in" private_interface="out" name="Ca_ds"/>
<variable units="millimolar" public_interface="in" name="K_o"/>
<variable units="millimolar" public_interface="in" name="K_i"/>
<variable units="millimolar" public_interface="in" name="Na_o"/>
<variable units="millimolar" public_interface="in" name="Na_i"/>
<variable units="millijoule_per_mole_kelvin" public_interface="in" name="R"/>
<variable units="coulomb_per_mole" public_interface="in" name="F"/>
<variable units="kelvin" public_interface="in" name="T"/>
<variable units="second" public_interface="in" private_interface="out" name="time"/>
<variable units="millivolt" public_interface="in" private_interface="out" name="V"/>
<variable units="dimensionless" private_interface="in" name="d"/>
<variable units="dimensionless" private_interface="in" name="f"/>
<variable units="dimensionless" private_interface="in" name="f2"/>
<variable units="dimensionless" private_interface="in" name="f2ds"/>
<variable units="millimolar" private_interface="out" name="Km_f2" initial_value="100000"/>
<variable units="millimolar" private_interface="out" name="Km_f2ds" initial_value="0.001"/>
<variable units="millimolar_per_second" public_interface="out" private_interface="out" name="R_decay" initial_value="20"/>
<variable units="dimensionless" name="FrICa" initial_value="1"/>
<math xmlns="http://www.w3.org/1998/Math/MathML">
<apply>
<eq/>
<ci>i_Ca_L_Ca_cyt</ci>
<apply>
<times/>
<apply>
<divide/>
<apply>
<divide/>
<apply>
<times/>
<apply>
<minus/>
<cn cellml:units="dimensionless">1</cn>
<ci>FrICa</ci>
</apply>
<cn cellml:units="dimensionless">4</cn>
<ci>P_Ca_L</ci>
<ci>d</ci>
<ci>f</ci>
<ci>f2</ci>
<apply>
<minus/>
<ci>V</ci>
<cn cellml:units="millivolt">50</cn>
</apply>
<ci>F</ci>
</apply>
<apply>
<times/>
<ci>R</ci>
<ci>T</ci>
</apply>
</apply>
<apply>
<minus/>
<cn cellml:units="dimensionless">1</cn>
<apply>
<exp/>
<apply>
<divide/>
<apply>
<times/>
<apply>
<minus/>
<apply>
<minus/>
<ci>V</ci>
<cn cellml:units="millivolt">50</cn>
</apply>
</apply>
<ci>F</ci>
<cn cellml:units="dimensionless">2</cn>
</apply>
<apply>
<times/>
<ci>R</ci>
<ci>T</ci>
</apply>
</apply>
</apply>
</apply>
</apply>
<apply>
<minus/>
<apply>
<times/>
<ci>Ca_i</ci>
<apply>
<exp/>
<apply>
<divide/>
<apply>
<times/>
<cn cellml:units="millijoule_per_coulomb">100</cn>
<ci>F</ci>
</apply>
<apply>
<times/>
<ci>R</ci>
<ci>T</ci>
</apply>
</apply>
</apply>
</apply>
<apply>
<times/>
<ci>Ca_o</ci>
<apply>
<exp/>
<apply>
<divide/>
<apply>
<times/>
<apply>
<minus/>
<apply>
<minus/>
<ci>V</ci>
<cn cellml:units="millivolt">50</cn>
</apply>
</apply>
<ci>F</ci>
<cn cellml:units="dimensionless">2</cn>
</apply>
<apply>
<times/>
<ci>R</ci>
<ci>T</ci>
</apply>
</apply>
</apply>
</apply>
</apply>
</apply>
</apply>
<apply>
<eq/>
<ci>i_Ca_L_K_cyt</ci>
<apply>
<times/>
<apply>
<divide/>
<apply>
<divide/>
<apply>
<times/>
<apply>
<minus/>
<cn cellml:units="dimensionless">1</cn>
<ci>FrICa</ci>
</apply>
<ci>P_CaK</ci>
<ci>P_Ca_L</ci>
<ci>d</ci>
<ci>f</ci>
<ci>f2</ci>
<apply>
<minus/>
<ci>V</ci>
<cn cellml:units="millivolt">50</cn>
</apply>
<ci>F</ci>
</apply>
<apply>
<times/>
<ci>R</ci>
<ci>T</ci>
</apply>
</apply>
<apply>
<minus/>
<cn cellml:units="dimensionless">1</cn>
<apply>
<exp/>
<apply>
<divide/>
<apply>
<times/>
<apply>
<minus/>
<apply>
<minus/>
<ci>V</ci>
<cn cellml:units="millivolt">50</cn>
</apply>
</apply>
<ci>F</ci>
</apply>
<apply>
<times/>
<ci>R</ci>
<ci>T</ci>
</apply>
</apply>
</apply>
</apply>
</apply>
<apply>
<minus/>
<apply>
<times/>
<ci>K_i</ci>
<apply>
<exp/>
<apply>
<divide/>
<apply>
<times/>
<cn cellml:units="millijoule_per_coulomb">50</cn>
<ci>F</ci>
</apply>
<apply>
<times/>
<ci>R</ci>
<ci>T</ci>
</apply>
</apply>
</apply>
</apply>
<apply>
<times/>
<ci>K_o</ci>
<apply>
<exp/>
<apply>
<divide/>
<apply>
<times/>
<apply>
<minus/>
<apply>
<minus/>
<ci>V</ci>
<cn cellml:units="millivolt">50</cn>
</apply>
</apply>
<ci>F</ci>
</apply>
<apply>
<times/>
<ci>R</ci>
<ci>T</ci>
</apply>
</apply>
</apply>
</apply>
</apply>
</apply>
</apply>
<apply>
<eq/>
<ci>i_Ca_L_Na_cyt</ci>
<apply>
<times/>
<apply>
<divide/>
<apply>
<divide/>
<apply>
<times/>
<apply>
<minus/>
<cn cellml:units="dimensionless">1</cn>
<ci>FrICa</ci>
</apply>
<ci>P_CaNa</ci>
<ci>P_Ca_L</ci>
<ci>d</ci>
<ci>f</ci>
<ci>f2</ci>
<apply>
<minus/>
<ci>V</ci>
<cn cellml:units="millivolt">50</cn>
</apply>
<ci>F</ci>
</apply>
<apply>
<times/>
<ci>R</ci>
<ci>T</ci>
</apply>
</apply>
<apply>
<minus/>
<cn cellml:units="dimensionless">1</cn>
<apply>
<exp/>
<apply>
<divide/>
<apply>
<times/>
<apply>
<minus/>
<apply>
<minus/>
<ci>V</ci>
<cn cellml:units="millivolt">50</cn>
</apply>
</apply>
<ci>F</ci>
</apply>
<apply>
<times/>
<ci>R</ci>
<ci>T</ci>
</apply>
</apply>
</apply>
</apply>
</apply>
<apply>
<minus/>
<apply>
<times/>
<ci>Na_i</ci>
<apply>
<exp/>
<apply>
<divide/>
<apply>
<times/>
<cn cellml:units="millijoule_per_coulomb">50</cn>
<ci>F</ci>
</apply>
<apply>
<times/>
<ci>R</ci>
<ci>T</ci>
</apply>
</apply>
</apply>
</apply>
<apply>
<times/>
<ci>Na_o</ci>
<apply>
<exp/>
<apply>
<divide/>
<apply>
<times/>
<apply>
<minus/>
<apply>
<minus/>
<ci>V</ci>
<cn cellml:units="millivolt">50</cn>
</apply>
</apply>
<ci>F</ci>
</apply>
<apply>
<times/>
<ci>R</ci>
<ci>T</ci>
</apply>
</apply>
</apply>
</apply>
</apply>
</apply>
</apply>
<apply>
<eq/>
<ci>i_Ca_L_Ca_ds</ci>
<apply>
<times/>
<apply>
<divide/>
<apply>
<divide/>
<apply>
<times/>
<ci>FrICa</ci>
<cn cellml:units="dimensionless">4</cn>
<ci>P_Ca_L</ci>
<ci>d</ci>
<ci>f</ci>
<ci>f2ds</ci>
<apply>
<minus/>
<ci>V</ci>
<cn cellml:units="millivolt">50</cn>
</apply>
<ci>F</ci>
</apply>
<apply>
<times/>
<ci>R</ci>
<ci>T</ci>
</apply>
</apply>
<apply>
<minus/>
<cn cellml:units="dimensionless">1</cn>
<apply>
<exp/>
<apply>
<divide/>
<apply>
<times/>
<apply>
<minus/>
<apply>
<minus/>
<ci>V</ci>
<cn cellml:units="millivolt">50</cn>
</apply>
</apply>
<ci>F</ci>
<cn cellml:units="dimensionless">2</cn>
</apply>
<apply>
<times/>
<ci>R</ci>
<ci>T</ci>
</apply>
</apply>
</apply>
</apply>
</apply>
<apply>
<minus/>
<apply>
<times/>
<ci>Ca_i</ci>
<apply>
<exp/>
<apply>
<divide/>
<apply>
<times/>
<cn cellml:units="millijoule_per_coulomb">100</cn>
<ci>F</ci>
</apply>
<apply>
<times/>
<ci>R</ci>
<ci>T</ci>
</apply>
</apply>
</apply>
</apply>
<apply>
<times/>
<ci>Ca_o</ci>
<apply>
<exp/>
<apply>
<divide/>
<apply>
<times/>
<apply>
<minus/>
<apply>
<minus/>
<ci>V</ci>
<cn cellml:units="millivolt">50</cn>
</apply>
</apply>
<ci>F</ci>
<cn cellml:units="dimensionless">2</cn>
</apply>
<apply>
<times/>
<ci>R</ci>
<ci>T</ci>
</apply>
</apply>
</apply>
</apply>
</apply>
</apply>
</apply>
<apply>
<eq/>
<ci>i_Ca_L_K_ds</ci>
<apply>
<times/>
<apply>
<divide/>
<apply>
<divide/>
<apply>
<times/>
<ci>FrICa</ci>
<ci>P_CaK</ci>
<ci>P_Ca_L</ci>
<ci>d</ci>
<ci>f</ci>
<ci>f2ds</ci>
<apply>
<minus/>
<ci>V</ci>
<cn cellml:units="millivolt">50</cn>
</apply>
<ci>F</ci>
</apply>
<apply>
<times/>
<ci>R</ci>
<ci>T</ci>
</apply>
</apply>
<apply>
<minus/>
<cn cellml:units="dimensionless">1</cn>
<apply>
<exp/>
<apply>
<divide/>
<apply>
<times/>
<apply>
<minus/>
<apply>
<minus/>
<ci>V</ci>
<cn cellml:units="millivolt">50</cn>
</apply>
</apply>
<ci>F</ci>
</apply>
<apply>
<times/>
<ci>R</ci>
<ci>T</ci>
</apply>
</apply>
</apply>
</apply>
</apply>
<apply>
<minus/>
<apply>
<times/>
<ci>K_i</ci>
<apply>
<exp/>
<apply>
<divide/>
<apply>
<times/>
<cn cellml:units="millijoule_per_coulomb">50</cn>
<ci>F</ci>
</apply>
<apply>
<times/>
<ci>R</ci>
<ci>T</ci>
</apply>
</apply>
</apply>
</apply>
<apply>
<times/>
<ci>K_o</ci>
<apply>
<exp/>
<apply>
<divide/>
<apply>
<times/>
<apply>
<minus/>
<apply>
<minus/>
<ci>V</ci>
<cn cellml:units="millivolt">50</cn>
</apply>
</apply>
<ci>F</ci>
</apply>
<apply>
<times/>
<ci>R</ci>
<ci>T</ci>
</apply>
</apply>
</apply>
</apply>
</apply>
</apply>
</apply>
<apply>
<eq/>
<ci>i_Ca_L_Na_ds</ci>
<apply>
<times/>
<apply>
<divide/>
<apply>
<divide/>
<apply>
<times/>
<ci>FrICa</ci>
<ci>P_CaNa</ci>
<ci>P_Ca_L</ci>
<ci>d</ci>
<ci>f</ci>
<ci>f2ds</ci>
<apply>
<minus/>
<ci>V</ci>
<cn cellml:units="millivolt">50</cn>
</apply>
<ci>F</ci>
</apply>
<apply>
<times/>
<ci>R</ci>
<ci>T</ci>
</apply>
</apply>
<apply>
<minus/>
<cn cellml:units="dimensionless">1</cn>
<apply>
<exp/>
<apply>
<divide/>
<apply>
<times/>
<apply>
<minus/>
<apply>
<minus/>
<ci>V</ci>
<cn cellml:units="millivolt">50</cn>
</apply>
</apply>
<ci>F</ci>
</apply>
<apply>
<times/>
<ci>R</ci>
<ci>T</ci>
</apply>
</apply>
</apply>
</apply>
</apply>
<apply>
<minus/>
<apply>
<times/>
<ci>Na_i</ci>
<apply>
<exp/>
<apply>
<divide/>
<apply>
<times/>
<cn cellml:units="millijoule_per_coulomb">50</cn>
<ci>F</ci>
</apply>
<apply>
<times/>
<ci>R</ci>
<ci>T</ci>
</apply>
</apply>
</apply>
</apply>
<apply>
<times/>
<ci>Na_o</ci>
<apply>
<exp/>
<apply>
<divide/>
<apply>
<times/>
<apply>
<minus/>
<apply>
<minus/>
<ci>V</ci>
<cn cellml:units="millivolt">50</cn>
</apply>
</apply>
<ci>F</ci>
</apply>
<apply>
<times/>
<ci>R</ci>
<ci>T</ci>
</apply>
</apply>
</apply>
</apply>
</apply>
</apply>
</apply>
<apply>
<eq/>
<ci>i_Ca_L</ci>
<apply>
<plus/>
<ci>i_Ca_L_Ca_cyt</ci>
<ci>i_Ca_L_K_cyt</ci>
<ci>i_Ca_L_Na_cyt</ci>
<ci>i_Ca_L_Ca_ds</ci>
<ci>i_Ca_L_K_ds</ci>
<ci>i_Ca_L_Na_ds</ci>
</apply>
</apply>
</math>
</component>
<component name="L_type_Ca_channel_d_gate">
<variable units="dimensionless" public_interface="out" name="d" initial_value="0"/>
<variable units="per_second" name="alpha_d"/>
<variable units="per_second" name="beta_d"/>
<variable units="millivolt" public_interface="in" name="V"/>
<variable units="second" public_interface="in" name="time"/>
<variable units="millivolt" name="E0_d"/>
<variable units="dimensionless" name="speed_d" initial_value="3"/>
<math xmlns="http://www.w3.org/1998/Math/MathML">
<apply>
<eq/>
<ci>E0_d</ci>
<apply>
<minus/>
<apply>
<plus/>
<ci>V</ci>
<cn cellml:units="millivolt">24</cn>
</apply>
<cn cellml:units="millivolt">5</cn>
</apply>
</apply>
<apply>
<eq/>
<ci>alpha_d</ci>
<piecewise>
<piece>
<cn cellml:units="per_second">120</cn>
<apply>
<lt/>
<apply>
<abs/>
<ci>E0_d</ci>
</apply>
<cn cellml:units="millivolt">0.0001</cn>
</apply>
</piece>
<otherwise>
<apply>
<divide/>
<apply>
<times/>
<cn cellml:units="per_millivolt_second">30</cn>
<ci>E0_d</ci>
</apply>
<apply>
<minus/>
<cn cellml:units="dimensionless">1</cn>
<apply>
<exp/>
<apply>
<divide/>
<apply>
<minus/>
<ci>E0_d</ci>
</apply>
<cn cellml:units="millivolt">4</cn>
</apply>
</apply>
</apply>
</apply>
</otherwise>
</piecewise>
</apply>
<apply>
<eq/>
<ci>beta_d</ci>
<piecewise>
<piece>
<cn cellml:units="per_second">120</cn>
<apply>
<lt/>
<apply>
<abs/>
<ci>E0_d</ci>
</apply>
<cn cellml:units="millivolt">0.0001</cn>
</apply>
</piece>
<otherwise>
<apply>
<divide/>
<apply>
<times/>
<cn cellml:units="per_millivolt_second">12</cn>
<ci>E0_d</ci>
</apply>
<apply>
<minus/>
<apply>
<exp/>
<apply>
<divide/>
<ci>E0_d</ci>
<cn cellml:units="millivolt">10</cn>
</apply>
</apply>
<cn cellml:units="dimensionless">1</cn>
</apply>
</apply>
</otherwise>
</piecewise>
</apply>
<apply>
<eq/>
<apply>
<diff/>
<bvar>
<ci>time</ci>
</bvar>
<ci>d</ci>
</apply>
<apply>
<times/>
<ci>speed_d</ci>
<apply>
<minus/>
<apply>
<times/>
<ci>alpha_d</ci>
<apply>
<minus/>
<cn cellml:units="dimensionless">1</cn>
<ci>d</ci>
</apply>
</apply>
<apply>
<times/>
<ci>beta_d</ci>
<ci>d</ci>
</apply>
</apply>
</apply>
</apply>
</math>
</component>
<component name="L_type_Ca_channel_f_gate">
<variable units="dimensionless" public_interface="out" name="f" initial_value="1"/>
<variable units="per_second" name="alpha_f"/>
<variable units="per_second" name="beta_f"/>
<variable units="millivolt" public_interface="in" name="V"/>
<variable units="second" public_interface="in" name="time"/>
<variable units="dimensionless" name="speed_f" initial_value="0.3"/>
<variable units="dimensionless" name="delta_f" initial_value="0.0001"/>
<variable units="millivolt" name="E0_f"/>
<math xmlns="http://www.w3.org/1998/Math/MathML">
<apply>
<eq/>
<ci>E0_f</ci>
<apply>
<plus/>
<ci>V</ci>
<cn cellml:units="millivolt">34</cn>
</apply>
</apply>
<apply>
<eq/>
<ci>alpha_f</ci>
<piecewise>
<piece>
<cn cellml:units="per_second">25</cn>
<apply>
<lt/>
<apply>
<abs/>
<ci>E0_f</ci>
</apply>
<ci>delta_f</ci>
</apply>
</piece>
<otherwise>
<apply>
<divide/>
<apply>
<times/>
<cn cellml:units="per_millivolt_second">6.25</cn>
<ci>E0_f</ci>
</apply>
<apply>
<minus/>
<apply>
<exp/>
<apply>
<divide/>
<ci>E0_f</ci>
<cn cellml:units="millivolt">4</cn>
</apply>
</apply>
<cn cellml:units="dimensionless">1</cn>
</apply>
</apply>
</otherwise>
</piecewise>
</apply>
<apply>
<eq/>
<ci>beta_f</ci>
<apply>
<divide/>
<cn cellml:units="per_second">12</cn>
<apply>
<plus/>
<cn cellml:units="dimensionless">1</cn>
<apply>
<exp/>
<apply>
<divide/>
<apply>
<times/>
<apply>
<minus/>
<cn cellml:units="dimensionless">1</cn>
</apply>
<apply>
<plus/>
<ci>V</ci>
<cn cellml:units="millivolt">34</cn>
</apply>
</apply>
<cn cellml:units="millivolt">4</cn>
</apply>
</apply>
</apply>
</apply>
</apply>
<apply>
<eq/>
<apply>
<diff/>
<bvar>
<ci>time</ci>
</bvar>
<ci>f</ci>
</apply>
<apply>
<times/>
<ci>speed_f</ci>
<apply>
<minus/>
<apply>
<times/>
<ci>alpha_f</ci>
<apply>
<minus/>
<cn cellml:units="dimensionless">1</cn>
<ci>f</ci>
</apply>
</apply>
<apply>
<times/>
<ci>beta_f</ci>
<ci>f</ci>
</apply>
</apply>
</apply>
</apply>
</math>
</component>
<component name="L_type_Ca_channel_f2_gate">
<variable units="dimensionless" public_interface="out" name="f2" initial_value="0.9349197"/>
<variable units="millimolar" public_interface="in" name="Km_f2"/>
<variable units="millimolar" public_interface="in" name="Ca_i"/>
<variable units="millivolt" public_interface="in" name="V"/>
<variable units="second" public_interface="in" name="time"/>
<math xmlns="http://www.w3.org/1998/Math/MathML">
<apply>
<eq/>
<apply>
<diff/>
<bvar>
<ci>time</ci>
</bvar>
<ci>f2</ci>
</apply>
<apply>
<minus/>
<cn cellml:units="dimensionless">1</cn>
<apply>
<plus/>
<apply>
<divide/>
<ci>Ca_i</ci>
<apply>
<plus/>
<ci>Km_f2</ci>
<ci>Ca_i</ci>
</apply>
</apply>
<ci>f2</ci>
</apply>
</apply>
</apply>
</math>
</component>
<component name="L_type_Ca_channel_f2ds_gate">
<variable units="dimensionless" public_interface="out" name="f2ds" initial_value="0.9651958"/>
<variable units="millimolar" public_interface="in" name="Km_f2ds"/>
<variable units="millimolar_per_second" public_interface="in" name="R_decay"/>
<variable units="millimolar" public_interface="in" name="Ca_ds"/>
<variable units="millivolt" public_interface="in" name="V"/>
<variable units="second" public_interface="in" name="time"/>
<math xmlns="http://www.w3.org/1998/Math/MathML">
<apply>
<eq/>
<apply>
<diff/>
<bvar>
<ci>time</ci>
</bvar>
<ci>f2ds</ci>
</apply>
<apply>
<times/>
<ci>R_decay</ci>
<apply>
<minus/>
<cn cellml:units="dimensionless">1</cn>
<apply>
<plus/>
<apply>
<divide/>
<ci>Ca_ds</ci>
<apply>
<plus/>
<ci>Km_f2ds</ci>
<ci>Ca_ds</ci>
</apply>
</apply>
<ci>f2ds</ci>
</apply>
</apply>
</apply>
</apply>
</math>
</component>
<component name="calcium_background_current">
<variable units="nanoamp" public_interface="out" name="i_b_Ca"/>
<variable units="microS" name="g_bca" initial_value="0.00025"/>
<variable units="millivolt" public_interface="in" name="E_Ca"/>
<variable units="second" public_interface="in" name="time"/>
<variable units="millivolt" public_interface="in" name="V"/>
<math xmlns="http://www.w3.org/1998/Math/MathML">
<apply>
<eq/>
<ci>i_b_Ca</ci>
<apply>
<times/>
<ci>g_bca</ci>
<apply>
<minus/>
<ci>V</ci>
<ci>E_Ca</ci>
</apply>
</apply>
</apply>
</math>
</component>
<component name="transient_outward_current">
<variable units="nanoamp" public_interface="out" name="i_to"/>
<variable units="microS" name="g_to" initial_value="0.005"/>
<variable units="microS" name="g_tos" initial_value="0"/>
<variable units="millivolt" public_interface="in" name="E_K"/>
<variable units="millivolt" public_interface="in" private_interface="out" name="V"/>
<variable units="second" public_interface="in" private_interface="out" name="time"/>
<variable units="dimensionless" private_interface="in" name="s"/>
<variable units="dimensionless" private_interface="in" name="r"/>
<math xmlns="http://www.w3.org/1998/Math/MathML">
<apply>
<eq/>
<ci>i_to</ci>
<apply>
<times/>
<ci>g_to</ci>
<apply>
<plus/>
<ci>g_tos</ci>
<apply>
<times/>
<ci>s</ci>
<apply>
<minus/>
<cn cellml:units="dimensionless">1</cn>
<ci>g_tos</ci>
</apply>
</apply>
</apply>
<ci>r</ci>
<apply>
<minus/>
<ci>V</ci>
<ci>E_K</ci>
</apply>
</apply>
</apply>
</math>
</component>
<component name="transient_outward_current_s_gate">
<variable units="dimensionless" public_interface="out" name="s" initial_value="0.9948645"/>
<variable units="per_second" name="alpha_s"/>
<variable units="per_second" name="beta_s"/>
<variable units="millivolt" public_interface="in" name="V"/>
<variable units="second" public_interface="in" name="time"/>
<math xmlns="http://www.w3.org/1998/Math/MathML">
<apply>
<eq/>
<ci>alpha_s</ci>
<apply>
<times/>
<cn cellml:units="per_second">0.033</cn>
<apply>
<exp/>
<apply>
<divide/>
<apply>
<minus/>
<ci>V</ci>
</apply>
<cn cellml:units="millivolt">17</cn>
</apply>
</apply>
</apply>
</apply>
<apply>
<eq/>
<ci>beta_s</ci>
<apply>
<divide/>
<cn cellml:units="per_second">33</cn>
<apply>
<plus/>
<cn cellml:units="dimensionless">1</cn>
<apply>
<exp/>
<apply>
<times/>
<apply>
<minus/>
<cn cellml:units="dimensionless">0.125</cn>
</apply>
<apply>
<plus/>
<ci>V</ci>
<cn cellml:units="millivolt">10</cn>
</apply>
</apply>
</apply>
</apply>
</apply>
</apply>
<apply>
<eq/>
<apply>
<diff/>
<bvar>
<ci>time</ci>
</bvar>
<ci>s</ci>
</apply>
<apply>
<minus/>
<apply>
<times/>
<ci>alpha_s</ci>
<apply>
<minus/>
<cn cellml:units="dimensionless">1</cn>
<ci>s</ci>
</apply>
</apply>
<apply>
<times/>
<ci>beta_s</ci>
<ci>s</ci>
</apply>
</apply>
</apply>
</math>
</component>
<component name="transient_outward_current_r_gate">
<variable units="dimensionless" public_interface="out" name="r" initial_value="0"/>
<variable units="millivolt" public_interface="in" name="V"/>
<variable units="second" public_interface="in" name="time"/>
<math xmlns="http://www.w3.org/1998/Math/MathML">
<apply>
<eq/>
<apply>
<diff/>
<bvar>
<ci>time</ci>
</bvar>
<ci>r</ci>
</apply>
<apply>
<times/>
<cn cellml:units="per_second">333</cn>
<apply>
<minus/>
<apply>
<divide/>
<cn cellml:units="dimensionless">1</cn>
<apply>
<plus/>
<cn cellml:units="dimensionless">1</cn>
<apply>
<exp/>
<apply>
<divide/>
<apply>
<minus/>
<apply>
<plus/>
<ci>V</ci>
<cn cellml:units="millivolt">4</cn>
</apply>
</apply>
<cn cellml:units="dimensionless">5</cn>
</apply>
</apply>
</apply>
</apply>
<ci>r</ci>
</apply>
</apply>
</apply>
</math>
</component>
<component name="sodium_potassium_pump">
<variable units="nanoamp" public_interface="out" name="i_NaK"/>
<variable units="nanoamp" name="i_NaK_max" initial_value="0.7"/>
<variable units="millimolar" name="K_mK" initial_value="1"/>
<variable units="millimolar" name="K_mNa" initial_value="40"/>
<variable units="millimolar" public_interface="in" name="K_o"/>
<variable units="millimolar" public_interface="in" name="Na_i"/>
<variable units="second" public_interface="in" name="time"/>
<math xmlns="http://www.w3.org/1998/Math/MathML">
<apply>
<eq/>
<ci>i_NaK</ci>
<apply>
<divide/>
<apply>
<times/>
<apply>
<divide/>
<apply>
<times/>
<ci>i_NaK_max</ci>
<ci>K_o</ci>
</apply>
<apply>
<plus/>
<ci>K_mK</ci>
<ci>K_o</ci>
</apply>
</apply>
<ci>Na_i</ci>
</apply>
<apply>
<plus/>
<ci>K_mNa</ci>
<ci>Na_i</ci>
</apply>
</apply>
</apply>
</math>
</component>
<component name="sodium_calcium_exchanger">
<variable units="nanoamp" public_interface="out" name="i_NaCa"/>
<variable units="nanoamp" public_interface="out" name="i_NaCa_cyt"/>
<variable units="nanoamp" public_interface="out" name="i_NaCa_ds"/>
<variable units="nanoamp" name="k_NaCa" initial_value="0.0005"/>
<variable units="dimensionless" name="n_NaCa" initial_value="3"/>
<variable units="dimensionless" name="d_NaCa" initial_value="0"/>
<variable units="dimensionless" name="gamma" initial_value="0.5"/>
<variable units="dimensionless" name="FRiNaCa" initial_value="0.001"/>
<variable units="millimolar" public_interface="in" name="Na_i"/>
<variable units="millimolar" public_interface="in" name="Na_o"/>
<variable units="millimolar" public_interface="in" name="Ca_i"/>
<variable units="millimolar" public_interface="in" name="Ca_ds"/>
<variable units="millimolar" public_interface="in" name="Ca_o"/>
<variable units="millijoule_per_mole_kelvin" public_interface="in" name="R"/>
<variable units="coulomb_per_mole" public_interface="in" name="F"/>
<variable units="kelvin" public_interface="in" name="T"/>
<variable units="millivolt" public_interface="in" name="V"/>
<variable units="second" public_interface="in" name="time"/>
<math xmlns="http://www.w3.org/1998/Math/MathML">
<apply>
<eq/>
<ci>i_NaCa_cyt</ci>
<apply>
<divide/>
<apply>
<times/>
<apply>
<minus/>
<cn cellml:units="dimensionless">1</cn>
<ci>FRiNaCa</ci>
</apply>
<ci>k_NaCa</ci>
<apply>
<minus/>
<apply>
<times/>
<apply>
<exp/>
<apply>
<divide/>
<apply>
<times/>
<ci>gamma</ci>
<apply>
<minus/>
<ci>n_NaCa</ci>
<cn cellml:units="dimensionless">2</cn>
</apply>
<ci>V</ci>
<ci>F</ci>
</apply>
<apply>
<times/>
<ci>R</ci>
<ci>T</ci>
</apply>
</apply>
</apply>
<apply>
<power/>
<ci>Na_i</ci>
<ci>n_NaCa</ci>
</apply>
<ci>Ca_o</ci>
</apply>
<apply>
<times/>
<apply>
<exp/>
<apply>
<divide/>
<apply>
<times/>
<apply>
<minus/>
<ci>gamma</ci>
<cn cellml:units="dimensionless">1</cn>
</apply>
<apply>
<minus/>
<ci>n_NaCa</ci>
<cn cellml:units="dimensionless">2</cn>
</apply>
<ci>V</ci>
<ci>F</ci>
</apply>
<apply>
<times/>
<ci>R</ci>
<ci>T</ci>
</apply>
</apply>
</apply>
<apply>
<power/>
<ci>Na_o</ci>
<ci>n_NaCa</ci>
</apply>
<ci>Ca_i</ci>
</apply>
</apply>
</apply>
<apply>
<times/>
<apply>
<plus/>
<cn cellml:units="dimensionless">1</cn>
<apply>
<times/>
<ci>d_NaCa</ci>
<apply>
<plus/>
<apply>
<times/>
<ci>Ca_i</ci>
<apply>
<power/>
<ci>Na_o</ci>
<ci>n_NaCa</ci>
</apply>
</apply>
<apply>
<times/>
<ci>Ca_o</ci>
<apply>
<power/>
<ci>Na_i</ci>
<ci>n_NaCa</ci>
</apply>
</apply>
</apply>
</apply>
</apply>
<apply>
<plus/>
<cn cellml:units="dimensionless">1</cn>
<apply>
<divide/>
<ci>Ca_i</ci>
<cn cellml:units="millimolar">0.0069</cn>
</apply>
</apply>
</apply>
</apply>
</apply>
<apply>
<eq/>
<ci>i_NaCa_ds</ci>
<apply>
<divide/>
<apply>
<times/>
<ci>FRiNaCa</ci>
<ci>k_NaCa</ci>
<apply>
<minus/>
<apply>
<times/>
<apply>
<exp/>
<apply>
<divide/>
<apply>
<times/>
<ci>gamma</ci>
<apply>
<minus/>
<ci>n_NaCa</ci>
<cn cellml:units="dimensionless">2</cn>
</apply>
<ci>V</ci>
<ci>F</ci>
</apply>
<apply>
<times/>
<ci>R</ci>
<ci>T</ci>
</apply>
</apply>
</apply>
<apply>
<power/>
<ci>Na_i</ci>
<ci>n_NaCa</ci>
</apply>
<ci>Ca_o</ci>
</apply>
<apply>
<times/>
<apply>
<exp/>
<apply>
<divide/>
<apply>
<times/>
<apply>
<minus/>
<ci>gamma</ci>
<cn cellml:units="dimensionless">1</cn>
</apply>
<apply>
<minus/>
<ci>n_NaCa</ci>
<cn cellml:units="dimensionless">2</cn>
</apply>
<ci>V</ci>
<ci>F</ci>
</apply>
<apply>
<times/>
<ci>R</ci>
<ci>T</ci>
</apply>
</apply>
</apply>
<apply>
<power/>
<ci>Na_o</ci>
<ci>n_NaCa</ci>
</apply>
<ci>Ca_ds</ci>
</apply>
</apply>
</apply>
<apply>
<times/>
<apply>
<plus/>
<cn cellml:units="dimensionless">1</cn>
<apply>
<times/>
<ci>d_NaCa</ci>
<apply>
<plus/>
<apply>
<times/>
<ci>Ca_ds</ci>
<apply>
<power/>
<ci>Na_o</ci>
<ci>n_NaCa</ci>
</apply>
</apply>
<apply>
<times/>
<ci>Ca_o</ci>
<apply>
<power/>
<ci>Na_i</ci>
<ci>n_NaCa</ci>
</apply>
</apply>
</apply>
</apply>
</apply>
<apply>
<plus/>
<cn cellml:units="dimensionless">1</cn>
<apply>
<divide/>
<ci>Ca_ds</ci>
<cn cellml:units="millimolar">0.0069</cn>
</apply>
</apply>
</apply>
</apply>
</apply>
<apply>
<eq/>
<ci>i_NaCa</ci>
<apply>
<plus/>
<ci>i_NaCa_cyt</ci>
<ci>i_NaCa_ds</ci>
</apply>
</apply>
</math>
</component>
<component name="sarcoplasmic_reticulum_calcium_pump">
<variable units="millimolar_per_second" public_interface="out" name="i_up"/>
<variable units="per_second" name="K_1"/>
<variable units="per_second" name="K_2"/>
<variable units="millimolar" name="K_cyca" initial_value="0.0003"/>
<variable units="millimolar" name="K_xcs" initial_value="0.4"/>
<variable units="millimolar" name="K_srca" initial_value="0.5"/>
<variable units="per_second" name="alpha_up" initial_value="0.4"/>
<variable units="per_second" name="beta_up" initial_value="0.03"/>
<variable units="millimolar" public_interface="in" name="Ca_i"/>
<variable units="millimolar" public_interface="in" name="Ca_up"/>
<variable units="second" public_interface="in" name="time"/>
<math xmlns="http://www.w3.org/1998/Math/MathML">
<apply>
<eq/>
<ci>K_1</ci>
<apply>
<divide/>
<apply>
<times/>
<ci>K_cyca</ci>
<ci>K_xcs</ci>
</apply>
<ci>K_srca</ci>
</apply>
</apply>
<apply>
<eq/>
<ci>K_2</ci>
<apply>
<plus/>
<ci>Ca_i</ci>
<apply>
<times/>
<ci>Ca_up</ci>
<ci>K_1</ci>
</apply>
<apply>
<times/>
<ci>K_cyca</ci>
<ci>K_xcs</ci>
</apply>
<ci>K_cyca</ci>
</apply>
</apply>
<apply>
<eq/>
<ci>i_up</ci>
<apply>
<minus/>
<apply>
<times/>
<apply>
<divide/>
<ci>Ca_i</ci>
<ci>K_2</ci>
</apply>
<ci>alpha_up</ci>
</apply>
<apply>
<times/>
<apply>
<divide/>
<apply>
<times/>
<ci>Ca_up</ci>
<ci>K_1</ci>
</apply>
<ci>K_2</ci>
</apply>
<ci>beta_up</ci>
</apply>
</apply>
</apply>
</math>
</component>
<component name="calcium_translocation">
<variable units="millimolar_per_second" public_interface="out" name="i_trans"/>
<variable units="millimolar" public_interface="in" name="Ca_rel"/>
<variable units="millimolar" public_interface="in" name="Ca_up"/>
<variable units="second" public_interface="in" name="time"/>
<math xmlns="http://www.w3.org/1998/Math/MathML">
<apply>
<eq/>
<ci>i_trans</ci>
<apply>
<times/>
<cn cellml:units="per_second">50</cn>
<apply>
<minus/>
<ci>Ca_up</ci>
<ci>Ca_rel</ci>
</apply>
</apply>
</apply>
</math>
</component>
<component name="calcium_release">
<variable units="millimolar_per_second" public_interface="out" name="i_rel"/>
<variable units="millivolt" name="VoltDep"/>
<variable units="dimensionless" name="RegBindSite"/>
<variable units="dimensionless" name="CaiReg"/>
<variable units="dimensionless" name="CadsReg"/>
<variable units="per_second" name="ActRate"/>
<variable units="per_second" name="InactRate"/>
<variable units="per_second" name="K_leak_rate" initial_value="0.05"/>
<variable units="per_second" name="K_m_rel" initial_value="250"/>
<variable units="millimolar" name="K_m_Ca_cyt" initial_value="0.0005"/>
<variable units="millimolar" name="K_m_Ca_ds" initial_value="0.01"/>
<variable units="dimensionless" name="PrecFrac"/>
<variable units="dimensionless" name="ActFrac" initial_value="0.0042614"/>
<variable units="dimensionless" name="ProdFrac" initial_value="0.4068154"/>
<variable units="dimensionless" name="SpeedRel"/>
<variable units="second" public_interface="in" name="time"/>
<variable units="millivolt" public_interface="in" name="V"/>
<variable units="millimolar" public_interface="in" name="Ca_i"/>
<variable units="millimolar" public_interface="in" name="Ca_ds"/>
<variable units="millimolar" public_interface="in" name="Ca_rel"/>
<math xmlns="http://www.w3.org/1998/Math/MathML">
<apply>
<eq/>
<ci>VoltDep</ci>
<apply>
<exp/>
<apply>
<times/>
<cn cellml:units="dimensionless">0.08</cn>
<apply>
<minus/>
<ci>V</ci>
<cn cellml:units="millivolt">40</cn>
</apply>
</apply>
</apply>
</apply>
<apply>
<eq/>
<ci>CaiReg</ci>
<apply>
<divide/>
<ci>Ca_i</ci>
<apply>
<plus/>
<ci>Ca_i</ci>
<ci>K_m_Ca_cyt</ci>
</apply>
</apply>
</apply>
<apply>
<eq/>
<ci>CadsReg</ci>
<apply>
<divide/>
<ci>Ca_ds</ci>
<apply>
<plus/>
<ci>Ca_ds</ci>
<ci>K_m_Ca_ds</ci>
</apply>
</apply>
</apply>
<apply>
<eq/>
<ci>RegBindSite</ci>
<apply>
<plus/>
<ci>CaiReg</ci>
<apply>
<times/>
<apply>
<minus/>
<cn cellml:units="dimensionless">1</cn>
<ci>CaiReg</ci>
</apply>
<ci>CadsReg</ci>
</apply>
</apply>
</apply>
<apply>
<eq/>
<ci>ActRate</ci>
<apply>
<plus/>
<apply>
<times/>
<cn cellml:units="per_millivolt_second">0</cn>
<ci>VoltDep</ci>
</apply>
<apply>
<times/>
<cn cellml:units="per_second">500</cn>
<apply>
<power/>
<ci>RegBindSite</ci>
<cn cellml:units="dimensionless">2</cn>
</apply>
</apply>
</apply>
</apply>
<apply>
<eq/>
<ci>InactRate</ci>
<apply>
<plus/>
<cn cellml:units="per_second">60</cn>
<apply>
<times/>
<cn cellml:units="per_second">500</cn>
<apply>
<power/>
<ci>RegBindSite</ci>
<cn cellml:units="dimensionless">2</cn>
</apply>
</apply>
</apply>
</apply>
<apply>
<eq/>
<ci>SpeedRel</ci>
<piecewise>
<piece>
<cn cellml:units="dimensionless">5</cn>
<apply>
<lt/>
<ci>V</ci>
<apply>
<minus/>
<cn cellml:units="millivolt">50</cn>
</apply>
</apply>
</piece>
<otherwise>
<cn cellml:units="dimensionless">1</cn>
</otherwise>
</piecewise>
</apply>
<apply>
<eq/>
<ci>PrecFrac</ci>
<apply>
<minus/>
<apply>
<minus/>
<cn cellml:units="dimensionless">1</cn>
<ci>ActFrac</ci>
</apply>
<ci>ProdFrac</ci>
</apply>
</apply>
<apply>
<eq/>
<apply>
<diff/>
<bvar>
<ci>time</ci>
</bvar>
<ci>ActFrac</ci>
</apply>
<apply>
<minus/>
<apply>
<times/>
<ci>PrecFrac</ci>
<ci>SpeedRel</ci>
<ci>ActRate</ci>
</apply>
<apply>
<times/>
<ci>ActFrac</ci>
<ci>SpeedRel</ci>
<ci>InactRate</ci>
</apply>
</apply>
</apply>
<apply>
<eq/>
<apply>
<diff/>
<bvar>
<ci>time</ci>
</bvar>
<ci>ProdFrac</ci>
</apply>
<apply>
<minus/>
<apply>
<times/>
<ci>ActFrac</ci>
<ci>SpeedRel</ci>
<ci>InactRate</ci>
</apply>
<apply>
<times/>
<ci>SpeedRel</ci>
<ci>ProdFrac</ci>
</apply>
</apply>
</apply>
<apply>
<eq/>
<ci>i_rel</ci>
<apply>
<times/>
<apply>
<plus/>
<apply>
<times/>
<apply>
<power/>
<apply>
<divide/>
<ci>ActFrac</ci>
<apply>
<plus/>
<ci>ActFrac</ci>
<cn cellml:units="dimensionless">0.25</cn>
</apply>
</apply>
<cn cellml:units="dimensionless">2</cn>
</apply>
<ci>K_m_rel</ci>
</apply>
<ci>K_leak_rate</ci>
</apply>
<ci>Ca_rel</ci>
</apply>
</apply>
</math>
</component>
<component name="extracellular_sodium_concentration">
<variable units="millimolar" public_interface="out" name="Na_o" initial_value="140"/>
</component>
<component name="intracellular_sodium_concentration">
<variable units="millimolar" public_interface="out" name="Na_i" initial_value="7.3321223"/>
<variable units="microlitre" public_interface="in" name="V_i"/>
<variable units="second" public_interface="in" name="time"/>
<variable units="coulomb_per_mole" public_interface="in" name="F"/>
<variable units="nanoamp" public_interface="in" name="i_Na"/>
<variable units="nanoamp" public_interface="in" name="i_b_Na"/>
<variable units="nanoamp" public_interface="in" name="i_p_Na"/>
<variable units="nanoamp" public_interface="in" name="i_Ca_L_Na_cyt"/>
<variable units="nanoamp" public_interface="in" name="i_Ca_L_Na_ds"/>
<variable units="nanoamp" public_interface="in" name="i_NaK"/>
<variable units="nanoamp" public_interface="in" name="i_NaCa_cyt"/>
<math xmlns="http://www.w3.org/1998/Math/MathML">
<apply>
<eq/>
<apply>
<diff/>
<bvar>
<ci>time</ci>
</bvar>
<ci>Na_i</ci>
</apply>
<apply>
<times/>
<apply>
<divide/>
<apply>
<minus/>
<cn cellml:units="dimensionless">1</cn>
</apply>
<apply>
<times/>
<ci>V_i</ci>
<ci>F</ci>
</apply>
</apply>
<apply>
<plus/>
<ci>i_Na</ci>
<ci>i_p_Na</ci>
<ci>i_b_Na</ci>
<apply>
<times/>
<cn cellml:units="dimensionless">3</cn>
<ci>i_NaK</ci>
</apply>
<apply>
<times/>
<cn cellml:units="dimensionless">3</cn>
<ci>i_NaCa_cyt</ci>
</apply>
<ci>i_Ca_L_Na_cyt</ci>
<ci>i_Ca_L_Na_ds</ci>
</apply>
</apply>
</apply>
</math>
</component>
<component name="extracellular_calcium_concentration">
<variable units="millimolar" public_interface="out" name="Ca_o" initial_value="2"/>
</component>
<component name="extracellular_potassium_concentration">
<variable units="millimolar" public_interface="out" name="K_o" initial_value="4"/>
</component>
<component name="intracellular_potassium_concentration">
<variable units="millimolar" public_interface="out" name="K_i" initial_value="136.5644281"/>
<variable units="microlitre" public_interface="in" name="V_i"/>
<variable units="nanoamp" public_interface="in" name="i_K1"/>
<variable units="nanoamp" public_interface="in" name="i_Kr"/>
<variable units="nanoamp" public_interface="in" name="i_Ks"/>
<variable units="nanoamp" public_interface="in" name="i_Ca_L_K_cyt"/>
<variable units="nanoamp" public_interface="in" name="i_Ca_L_K_ds"/>
<variable units="nanoamp" public_interface="in" name="i_to"/>
<variable units="nanoamp" public_interface="in" name="i_NaK"/>
<variable units="second" public_interface="in" name="time"/>
<variable units="coulomb_per_mole" public_interface="in" name="F"/>
<math xmlns="http://www.w3.org/1998/Math/MathML">
<apply>
<eq/>
<apply>
<diff/>
<bvar>
<ci>time</ci>
</bvar>
<ci>K_i</ci>
</apply>
<apply>
<times/>
<apply>
<divide/>
<apply>
<minus/>
<cn cellml:units="dimensionless">1</cn>
</apply>
<apply>
<times/>
<ci>V_i</ci>
<ci>F</ci>
</apply>
</apply>
<apply>
<minus/>
<apply>
<plus/>
<ci>i_K1</ci>
<ci>i_Kr</ci>
<ci>i_Ks</ci>
<ci>i_Ca_L_K_cyt</ci>
<ci>i_Ca_L_K_ds</ci>
<ci>i_to</ci>
</apply>
<apply>
<times/>
<cn cellml:units="dimensionless">2</cn>
<ci>i_NaK</ci>
</apply>
</apply>
</apply>
</apply>
</math>
</component>
<component name="intracellular_calcium_concentration">
<variable units="millimolar" public_interface="out" name="Ca_i" initial_value="1.4e-5"/>
<variable units="millimolar" public_interface="out" name="Ca_ds" initial_value="1.88e-5"/>
<variable units="millimolar" public_interface="out" name="Ca_up" initial_value="0.4531889"/>
<variable units="millimolar" public_interface="out" name="Ca_rel" initial_value="0.4481927"/>
<variable units="millimolar" name="Ca_Calmod" initial_value="0.0005555"/>
<variable units="millimolar" name="Ca_Trop" initial_value="0.0003542"/>
<variable units="millimolar" name="Calmod" initial_value="0.02"/>
<variable units="millimolar" name="Trop" initial_value="0.05"/>
<variable units="per_second" name="alpha_Calmod" initial_value="100000"/>
<variable units="per_second" name="beta_Calmod" initial_value="50"/>
<variable units="per_second" name="alpha_Trop" initial_value="100000"/>
<variable units="per_second" name="beta_Trop" initial_value="200"/>
<variable units="micrometre" name="radius" initial_value="12"/>
<variable units="micrometre" name="length" initial_value="74"/>
<variable units="microlitre" public_interface="out" name="V_i"/>
<variable units="microlitre" name="V_Cell"/>
<variable units="dimensionless" name="V_i_ratio"/>
<variable units="dimensionless" name="V_ds_ratio" initial_value="0.1"/>
<variable units="dimensionless" name="V_rel_ratio" initial_value="0.1"/>
<variable units="dimensionless" name="V_e_ratio" initial_value="0.4"/>
<variable units="dimensionless" name="V_up_ratio" initial_value="0.01"/>
<variable units="second" name="Kdecay" initial_value="10"/>
<variable units="millimolar_per_second" public_interface="in" name="i_up"/>
<variable units="millimolar_per_second" public_interface="in" name="i_trans"/>
<variable units="millimolar_per_second" public_interface="in" name="i_rel"/>
<variable units="nanoamp" public_interface="in" name="i_NaCa_cyt"/>
<variable units="nanoamp" public_interface="in" name="i_NaCa_ds"/>
<variable units="nanoamp" public_interface="in" name="i_Ca_L_Ca_cyt"/>
<variable units="nanoamp" public_interface="in" name="i_Ca_L_Ca_ds"/>
<variable units="nanoamp" public_interface="in" name="i_b_Ca"/>
<variable units="coulomb_per_mole" public_interface="in" name="F"/>
<variable units="second" public_interface="in" name="time"/>
<math xmlns="http://www.w3.org/1998/Math/MathML">
<apply>
<eq/>
<ci>V_Cell</ci>
<apply>
<divide/>
<apply>
<times/>
<cn cellml:units="dimensionless">3.141592654</cn>
<apply>
<power/>
<apply>
<divide/>
<ci>radius</ci>
<cn cellml:units="dimensionless">1000</cn>
</apply>
<cn cellml:units="dimensionless">2</cn>
</apply>
<ci>length</ci>
</apply>
<cn cellml:units="dimensionless">1000</cn>
</apply>
</apply>
<apply>
<eq/>
<ci>V_i_ratio</ci>
<apply>
<minus/>
<apply>
<minus/>
<apply>
<minus/>
<cn cellml:units="dimensionless">1</cn>
<ci>V_e_ratio</ci>
</apply>
<ci>V_up_ratio</ci>
</apply>
<ci>V_rel_ratio</ci>
</apply>
</apply>
<apply>
<eq/>
<ci>V_i</ci>
<apply>
<times/>
<ci>V_Cell</ci>
<ci>V_i_ratio</ci>
</apply>
</apply>
<apply>
<eq/>
<apply>
<diff/>
<bvar>
<ci>time</ci>
</bvar>
<ci>Ca_i</ci>
</apply>
<apply>
<minus/>
<apply>
<minus/>
<apply>
<minus/>
<apply>
<plus/>
<apply>
<times/>
<apply>
<divide/>
<apply>
<minus/>
<cn cellml:units="dimensionless">1</cn>
</apply>
<apply>
<times/>
<cn cellml:units="dimensionless">2</cn>
<ci>V_i</ci>
<ci>F</ci>
</apply>
</apply>
<apply>
<minus/>
<apply>
<plus/>
<ci>i_Ca_L_Ca_cyt</ci>
<ci>i_b_Ca</ci>
</apply>
<apply>
<times/>
<cn cellml:units="dimensionless">2</cn>
<ci>i_NaCa_cyt</ci>
</apply>
</apply>
</apply>
<apply>
<times/>
<ci>Ca_ds</ci>
<ci>V_ds_ratio</ci>
<ci>Kdecay</ci>
</apply>
<apply>
<divide/>
<apply>
<times/>
<ci>i_rel</ci>
<ci>V_rel_ratio</ci>
</apply>
<ci>V_i_ratio</ci>
</apply>
</apply>
<apply>
<diff/>
<bvar>
<ci>time</ci>
</bvar>
<ci>Ca_Calmod</ci>
</apply>
</apply>
<apply>
<diff/>
<bvar>
<ci>time</ci>
</bvar>
<ci>Ca_Trop</ci>
</apply>
</apply>
<ci>i_up</ci>
</apply>
</apply>
<apply>
<eq/>
<apply>
<diff/>
<bvar>
<ci>time</ci>
</bvar>
<ci>Ca_ds</ci>
</apply>
<apply>
<minus/>
<apply>
<divide/>
<apply>
<minus/>
<ci>i_Ca_L_Ca_ds</ci>
</apply>
<apply>
<times/>
<cn cellml:units="dimensionless">2</cn>
<ci>V_ds_ratio</ci>
<ci>V_i</ci>
<ci>F</ci>
</apply>
</apply>
<apply>
<times/>
<ci>Ca_ds</ci>
<ci>Kdecay</ci>
</apply>
</apply>
</apply>
<apply>
<eq/>
<apply>
<diff/>
<bvar>
<ci>time</ci>
</bvar>
<ci>Ca_up</ci>
</apply>
<apply>
<minus/>
<apply>
<times/>
<apply>
<divide/>
<ci>V_i_ratio</ci>
<ci>V_up_ratio</ci>
</apply>
<ci>i_up</ci>
</apply>
<ci>i_trans</ci>
</apply>
</apply>
<apply>
<eq/>
<apply>
<diff/>
<bvar>
<ci>time</ci>
</bvar>
<ci>Ca_rel</ci>
</apply>
<apply>
<minus/>
<apply>
<times/>
<apply>
<divide/>
<ci>V_up_ratio</ci>
<ci>V_rel_ratio</ci>
</apply>
<ci>i_trans</ci>
</apply>
<ci>i_rel</ci>
</apply>
</apply>
<apply>
<eq/>
<apply>
<diff/>
<bvar>
<ci>time</ci>
</bvar>
<ci>Ca_Calmod</ci>
</apply>
<apply>
<minus/>
<apply>
<times/>
<ci>alpha_Calmod</ci>
<ci>Ca_i</ci>
<apply>
<minus/>
<ci>Calmod</ci>
<ci>Ca_Calmod</ci>
</apply>
</apply>
<apply>
<times/>
<ci>beta_Calmod</ci>
<ci>Ca_Calmod</ci>
</apply>
</apply>
</apply>
<apply>
<eq/>
<apply>
<diff/>
<bvar>
<ci>time</ci>
</bvar>
<ci>Ca_Trop</ci>
</apply>
<apply>
<minus/>
<apply>
<times/>
<ci>alpha_Trop</ci>
<ci>Ca_i</ci>
<apply>
<minus/>
<ci>Trop</ci>
<ci>Ca_Trop</ci>
</apply>
</apply>
<apply>
<times/>
<ci>beta_Trop</ci>
<ci>Ca_Trop</ci>
</apply>
</apply>
</apply>
</math>
</component>
<group>
<relationship_ref relationship="containment"/>
<component_ref component="membrane">
<component_ref component="fast_sodium_current">
<component_ref component="fast_sodium_current_m_gate"/>
<component_ref component="fast_sodium_current_h_gate"/>
</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_f2_gate"/>
<component_ref component="L_type_Ca_channel_f2ds_gate"/>
</component_ref>
<component_ref component="rapid_delayed_rectifier_potassium_current">
<component_ref component="rapid_delayed_rectifier_potassium_current_xr1_gate"/>
<component_ref component="rapid_delayed_rectifier_potassium_current_xr2_gate"/>
</component_ref>
<component_ref component="slow_delayed_rectifier_potassium_current">
<component_ref component="slow_delayed_rectifier_potassium_current_xs_gate"/>
</component_ref>
<component_ref component="time_independent_potassium_current"/>
<component_ref component="persistent_sodium_current"/>
<component_ref component="sodium_background_current"/>
<component_ref component="calcium_background_current"/>
<component_ref component="transient_outward_current">
<component_ref component="transient_outward_current_s_gate"/>
<component_ref component="transient_outward_current_r_gate"/>
</component_ref>
<component_ref component="sodium_potassium_pump"/>
<component_ref component="sodium_calcium_exchanger"/>
<component_ref component="sarcoplasmic_reticulum_calcium_pump"/>
<component_ref component="calcium_translocation"/>
<component_ref component="calcium_release"/>
<component_ref component="extracellular_sodium_concentration"/>
<component_ref component="intracellular_sodium_concentration"/>
<component_ref component="extracellular_potassium_concentration"/>
<component_ref component="intracellular_potassium_concentration"/>
<component_ref component="extracellular_calcium_concentration"/>
<component_ref component="intracellular_calcium_concentration"/>
<component_ref component="reversal_potentials"/>
</component_ref>
</group>
<group>
<relationship_ref relationship="encapsulation"/>
<component_ref component="fast_sodium_current">
<component_ref component="fast_sodium_current_m_gate"/>
<component_ref component="fast_sodium_current_h_gate"/>
</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_f2_gate"/>
<component_ref component="L_type_Ca_channel_f2ds_gate"/>
</component_ref>
<component_ref component="transient_outward_current">
<component_ref component="transient_outward_current_s_gate"/>
<component_ref component="transient_outward_current_r_gate"/>
</component_ref>
<component_ref component="rapid_delayed_rectifier_potassium_current">
<component_ref component="rapid_delayed_rectifier_potassium_current_xr1_gate"/>
<component_ref component="rapid_delayed_rectifier_potassium_current_xr2_gate"/>
</component_ref>
<component_ref component="slow_delayed_rectifier_potassium_current">
<component_ref component="slow_delayed_rectifier_potassium_current_xs_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="reversal_potentials"/>
<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="rapid_delayed_rectifier_potassium_current"/>
<map_variables variable_2="time" variable_1="time"/>
</connection>
<connection>
<map_components component_2="environment" component_1="slow_delayed_rectifier_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="persistent_sodium_current"/>
<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>
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<vCard:Other>unknown</vCard:Other>
</rdf:Description>
<rdf:Description rdf:about="rdf:#1ef60fab-d81b-4fce-95f0-1ea149acaae8">
<rdf:type rdf:resource="http://imc.org/vCard/3.0#internet"/>
<rdf:value>penny.noble@physiol.ox.ac.uk</rdf:value>
</rdf:Description>
<rdf:Description rdf:about="rdf:#fafda675-5f0f-4ea0-943c-252f43d7506e">
<vCard:Orgname>Oxford University</vCard:Orgname>
<vCard:Orgunit>unknown</vCard:Orgunit>
</rdf:Description>
<rdf:Description rdf:about="rdf:#ebff9468-7e1d-48d5-bd9a-914865e1f9af">
<vCard:ORG rdf:resource="rdf:#fafda675-5f0f-4ea0-943c-252f43d7506e"/>
<vCard:EMAIL rdf:resource="rdf:#1ef60fab-d81b-4fce-95f0-1ea149acaae8"/>
<vCard:N rdf:resource="rdf:#143d75c5-5ce5-4dd6-b9d1-cc8986cfae5c"/>
</rdf:Description>
<rdf:Description rdf:about="rdf:#7f2f8a88-a0f0-4285-b67d-ee171d003d69">
<dcterms:W3CDTF>1998-01-01</dcterms:W3CDTF>
</rdf:Description>
<rdf:Description rdf:about="rdf:#449ef549-1fc4-4510-8921-b82f6d1cdc64">
<vCard:N rdf:resource="rdf:#e801b2e9-efd4-4c27-a6c8-ab8db3d1fe92"/>
</rdf:Description>
</rdf:RDF>
</model>
