- Author:
- Hanne <Hanne@hanne-nielsens-macbook.local>
- Date:
- 2009-12-11 13:35:27+13:00
- Desc:
- Added images in ai and svg format, removed non pub med references
- Permanent Source URI:
- https://staging.physiomeproject.org/workspace/noble_varghese_kohl_noble_1998/rawfile/9a4240bfb9e47d801f5325696ae8222a1673631c/noble_varghese_kohl_noble_1998_c.cellml
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<!--
This CellML file was generated on 02/10/2007 at 16:53:35 using:
COR (0.9.31.793)
Copyright 2002-2007 Dr Alan Garny
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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<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 version has been curated and unit-checked by Penny Noble and is known to run in COR and PCEnv. This variant is the STRETCH model, which includes acetylcholine dependent modulation and the electromechanical processes simulated by Variant 02, and also includes simulation of stretch and fibroblasts. This model is parameterised the same as the BASIC model, with all additional variables set to zero. The values for these variables can be found in <ulink url="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=9487284&dopt=Abstract">Noble et al.'s 1998 paper.</ulink> This model is also associated with a PCEnv session file.
</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>
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, Denis Noble, Anthony Varghese, Peter Kohl and Penelope Noble, 1998, <emphasis>Can J Cardiol</emphasis>, 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>
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<title>cell diagram of Noble'98 model showing ionic currents, pumps and exchangers within the sarcolemma and the sarcoplasmic reticulum</title>
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<caption>A schematic diagram describing the current flows across the cell membrane that are captured in the Noble'98 model.</caption>
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</sect1>
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<cn cellml:units="dimensionless">2</cn>
</apply>
<apply>
<minus/>
<ci>V</ci>
<ci>E_Ks</ci>
</apply>
</apply>
</apply>
</math>
</component>
<component name="slow_delayed_rectifier_potassium_current_xs_gate">
<variable units="dimensionless" public_interface="out" name="xs" initial_value="0.001302"/>
<variable units="millivolt" public_interface="in" name="V"/>
<variable units="per_second" name="alpha_xs"/>
<variable units="per_second" name="beta_xs"/>
<variable units="second" public_interface="in" name="time"/>
<math xmlns="http://www.w3.org/1998/Math/MathML">
<apply>
<eq/>
<ci>alpha_xs</ci>
<apply>
<divide/>
<cn cellml:units="per_second">14</cn>
<apply>
<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="ATP_dependent_potassium_current">
<variable units="nanoA" public_interface="out" name="i_K_ATP"/>
<variable units="microS" name="g_K_ATP" initial_value="0"/>
<variable units="millimolar" name="K_ATP" initial_value="0.1"/>
<variable units="millimolar" name="ATP" 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/>
<ci>i_K_ATP</ci>
<apply>
<divide/>
<apply>
<times/>
<ci>g_K_ATP</ci>
<apply>
<plus/>
<ci>V</ci>
<cn cellml:units="millivolt">80</cn>
</apply>
</apply>
<apply>
<plus/>
<cn cellml:units="dimensionless">1</cn>
<apply>
<power/>
<apply>
<divide/>
<ci>ATP</ci>
<ci>K_ATP</ci>
</apply>
<cn cellml:units="dimensionless">2</cn>
</apply>
</apply>
</apply>
</apply>
</math>
</component>
<component name="sodium_activated_potassium_current">
<variable units="nanoA" public_interface="out" name="i_KNa"/>
<variable units="microS" name="g_K_Na" initial_value="0"/>
<variable units="millimolar" name="K_kna" initial_value="20"/>
<variable units="millimolar" public_interface="in" name="Na_i"/>
<variable units="millivolt" public_interface="in" name="E_K"/>
<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_KNa</ci>
<apply>
<times/>
<apply>
<divide/>
<apply>
<times/>
<ci>g_K_Na</ci>
<ci>Na_i</ci>
</apply>
<apply>
<plus/>
<ci>Na_i</ci>
<ci>K_kna</ci>
</apply>
</apply>
<apply>
<minus/>
<ci>V</ci>
<ci>E_K</ci>
</apply>
</apply>
</apply>
</math>
</component>
<component name="fast_sodium_current">
<variable units="nanoA" 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="millivolt" 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>
<ci>delta_m</ci>
</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="nanoA" 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="nanoA" 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="nanoA" public_interface="out" name="i_Ca_L_Ca_cyt"/>
<variable units="nanoA" public_interface="out" name="i_Ca_L_K_cyt"/>
<variable units="nanoA" public_interface="out" name="i_Ca_L_Na_cyt"/>
<variable units="nanoA" public_interface="out" name="i_Ca_L_Ca_ds"/>
<variable units="nanoA" public_interface="out" name="i_Ca_L_K_ds"/>
<variable units="nanoA" public_interface="out" name="i_Ca_L_Na_ds"/>
<variable units="nanoA" public_interface="out" name="i_Ca_L"/>
<variable units="nanoA_per_millimolar" name="P_Ca_L" initial_value="0.1"/>
<variable units="dimensionless" name="P_CaK" initial_value="0.002"/>
<variable units="dimensionless" 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="joule_per_kilomole_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="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="millivolt">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="millivolt">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="millivolt">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="millivolt">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="millivolt">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="millivolt">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="millivolt" 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="per_second">1</cn>
<apply>
<times/>
<cn cellml:units="per_second">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>
</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="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="nanoA" 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="nanoA" public_interface="out" name="i_to"/>
<variable units="microS" name="g_to" initial_value="0.005"/>
<variable units="dimensionless" 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="per_millivolt">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="millivolt">5</cn>
</apply>
</apply>
</apply>
</apply>
<ci>r</ci>
</apply>
</apply>
</apply>
</math>
</component>
<component name="ACh_dependent_potassium_current">
<variable units="nanoA" public_interface="out" name="i_K_ACh"/>
<variable units="microS" name="g_KACh" initial_value="0"/>
<variable units="millimolar" name="ACh" initial_value="5"/>
<variable units="millimolar" name="K_D" initial_value="0.00013"/>
<variable units="millivolt" public_interface="in" name="E_K"/>
<variable units="millimolar" public_interface="in" name="K_o"/>
<variable units="millimolar" public_interface="in" name="K_mk1"/>
<variable units="joule_per_kilomole_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" private_interface="out" name="time"/>
<variable units="dimensionless" private_interface="in" name="x_ACh"/>
<math xmlns="http://www.w3.org/1998/Math/MathML">
<apply>
<eq/>
<ci>i_K_ACh</ci>
<apply>
<divide/>
<apply>
<times/>
<ci>g_KACh</ci>
<apply>
<divide/>
<ci>K_o</ci>
<apply>
<plus/>
<ci>K_o</ci>
<ci>K_mk1</ci>
</apply>
</apply>
<ci>x_ACh</ci>
<apply>
<divide/>
<cn cellml:units="dimensionless">1</cn>
<apply>
<plus/>
<cn cellml:units="dimensionless">1</cn>
<apply>
<power/>
<apply>
<divide/>
<ci>K_D</ci>
<ci>ACh</ci>
</apply>
<cn cellml:units="dimensionless">2</cn>
</apply>
</apply>
</apply>
<apply>
<minus/>
<ci>V</ci>
<ci>E_K</ci>
</apply>
</apply>
<apply>
<plus/>
<cn cellml:units="dimensionless">1</cn>
<apply>
<exp/>
<apply>
<divide/>
<apply>
<times/>
<cn cellml:units="dimensionless">2</cn>
<ci>F</ci>
<apply>
<minus/>
<ci>V</ci>
<apply>
<plus/>
<ci>E_K</ci>
<cn cellml:units="millivolt">10</cn>
</apply>
</apply>
</apply>
<apply>
<times/>
<ci>R</ci>
<ci>T</ci>
</apply>
</apply>
</apply>
</apply>
</apply>
</apply>
</math>
</component>
<component name="ACh_dependent_potassium_current_xACh_gate">
<variable units="dimensionless" public_interface="out" name="x_ACh" initial_value="0"/>
<variable units="per_second" name="alpha_ACh" initial_value="0.5"/>
<variable units="per_second" name="beta_ACh" initial_value="0.5"/>
<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>x_ACh</ci>
</apply>
<apply>
<minus/>
<apply>
<times/>
<ci>alpha_ACh</ci>
<apply>
<minus/>
<cn cellml:units="dimensionless">1</cn>
<ci>x_ACh</ci>
</apply>
</apply>
<apply>
<times/>
<ci>beta_ACh</ci>
<ci>x_ACh</ci>
</apply>
</apply>
</apply>
</math>
</component>
<component name="sodium_potassium_pump">
<variable units="nanoA" public_interface="out" name="i_NaK"/>
<variable units="nanoA" 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="nanoA" public_interface="out" name="i_NaCa"/>
<variable units="nanoA" public_interface="out" name="i_NaCa_cyt"/>
<variable units="nanoA" public_interface="out" name="i_NaCa_ds"/>
<variable units="nanoA" 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="joule_per_kilomole_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="millimolar4">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="millimolar4">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="dimensionless" name="K_1"/>
<variable units="millimolar" name="K_2"/>
<variable units="millimolar" name="K_cyca" initial_value="0.0003"/>
<variable units="dimensionless" name="K_xcs" initial_value="0.4"/>
<variable units="millimolar" name="K_srca" initial_value="0.5"/>
<variable units="millimolar_per_second" name="alpha_up" initial_value="0.4"/>
<variable units="millimolar_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="dimensionless" 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="0.005"/>
<variable units="per_second" name="SRLeak"/>
<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="0.001914"/>
<variable units="dimensionless" name="ProdFrac" initial_value="0.2854569"/>
<variable units="dimensionless" name="SpeedRel"/>
<variable units="per_micrometre" name="gama_SR_SL" initial_value="2.5"/>
<variable units="dimensionless" name="gama_SR_IT" initial_value="2.5"/>
<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"/>
<variable units="dimensionless" public_interface="in" name="isometric_tension"/>
<variable units="micrometre" public_interface="in" name="sarcomere_length"/>
<math xmlns="http://www.w3.org/1998/Math/MathML">
<apply>
<eq/>
<ci>VoltDep</ci>
<apply>
<exp/>
<apply>
<times/>
<cn cellml:units="per_millivolt">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_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>SRLeak</ci>
<piecewise>
<piece>
<apply>
<times/>
<ci>K_leak_rate</ci>
<apply>
<exp/>
<apply>
<times/>
<ci>gama_SR_IT</ci>
<ci>isometric_tension</ci>
</apply>
</apply>
</apply>
<apply>
<gt/>
<ci>isometric_tension</ci>
<cn cellml:units="dimensionless">0</cn>
</apply>
</piece>
<otherwise>
<apply>
<times/>
<ci>K_leak_rate</ci>
<apply>
<exp/>
<apply>
<times/>
<ci>gama_SR_SL</ci>
<ci>sarcomere_length</ci>
</apply>
</apply>
</apply>
</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>
<cn cellml:units="per_second">1</cn>
<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>SRLeak</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="micrometre3" 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="nanoA" public_interface="in" name="i_Na"/>
<variable units="nanoA" public_interface="in" name="i_b_Na"/>
<variable units="nanoA" public_interface="in" name="i_p_Na"/>
<variable units="nanoA" public_interface="in" name="i_Ca_L_Na_cyt"/>
<variable units="nanoA" public_interface="in" name="i_Ca_L_Na_ds"/>
<variable units="nanoA" public_interface="in" name="i_NaK"/>
<variable units="nanoA" 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="mA_nA">1</cn>
</apply>
<apply>
<times/>
<cn cellml:units="litre_micrometre3">1</cn>
<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="micrometre3" public_interface="in" name="V_i"/>
<variable units="nanoA" public_interface="in" name="i_K1"/>
<variable units="nanoA" public_interface="in" name="i_Kr"/>
<variable units="nanoA" public_interface="in" name="i_Ks"/>
<variable units="nanoA" public_interface="in" name="i_Ca_L_K_cyt"/>
<variable units="nanoA" public_interface="in" name="i_Ca_L_K_ds"/>
<variable units="nanoA" public_interface="in" name="i_to"/>
<variable units="nanoA" 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="mA_nA">1</cn>
</apply>
<apply>
<times/>
<cn cellml:units="litre_micrometre3">1</cn>
<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" public_interface="out" name="Ca_Calmod" initial_value="0.0005555"/>
<variable units="millimolar" public_interface="out" name="Ca_Trop" initial_value="0.0002"/>
<variable units="millimolar" public_interface="out" name="Calmod" initial_value="0.02"/>
<variable units="millimolar" public_interface="out" name="Trop" initial_value="0.05"/>
<variable units="per_millimolar_second" name="alpha_Calmod" initial_value="100000"/>
<variable units="per_second" name="beta_Calmod" initial_value="50"/>
<variable units="per_millimolar_second" name="alpha_Trop"/>
<variable units="per_second" name="beta_Trop" initial_value="200"/>
<variable units="per_micrometre" name="gama_Trop_SL" initial_value="1.5"/>
<variable units="per_millimolar_second" name="KTrop" initial_value="5000"/>
<variable units="micrometre" name="radius" initial_value="12"/>
<variable units="micrometre" name="length" initial_value="74"/>
<variable units="micrometre3" public_interface="out" name="V_i"/>
<variable units="micrometre3" 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="per_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="nanoA" public_interface="in" name="i_NaCa_cyt"/>
<variable units="nanoA" public_interface="in" name="i_NaCa_ds"/>
<variable units="nanoA" public_interface="in" name="i_Ca_L_Ca_cyt"/>
<variable units="nanoA" public_interface="in" name="i_Ca_L_Ca_ds"/>
<variable units="nanoA" public_interface="in" name="i_b_Ca"/>
<variable units="coulomb_per_mole" public_interface="in" name="F"/>
<variable units="dimensionless" public_interface="in" name="isometric_tension"/>
<variable units="micrometre" public_interface="in" name="sarcomere_length"/>
<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="mA_nA">1</cn>
</apply>
<apply>
<times/>
<cn cellml:units="dimensionless">2</cn>
<cn cellml:units="litre_micrometre3">1</cn>
<ci>V_i</ci>
<ci>F</ci>
</apply>
</apply>
<apply>
<minus/>
<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>
<times/>
<cn cellml:units="dimensionless">2</cn>
<ci>i_NaCa_ds</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>
<times/>
<apply>
<minus/>
<cn cellml:units="mA_nA">1</cn>
</apply>
<ci>i_Ca_L_Ca_ds</ci>
</apply>
<apply>
<times/>
<cn cellml:units="dimensionless">2</cn>
<cn cellml:units="litre_micrometre3">1</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/>
<ci>alpha_Trop</ci>
<apply>
<times/>
<ci>KTrop</ci>
<apply>
<exp/>
<apply>
<times/>
<ci>gama_Trop_SL</ci>
<ci>sarcomere_length</ci>
</apply>
</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>
<component name="contraction">
<variable units="dimensionless" name="light_chain" initial_value="3.32e-5"/>
<variable units="dimensionless" name="cross_bridge" initial_value="8.09e-5"/>
<variable units="per_second" name="KCont1" initial_value="12000"/>
<variable units="dimensionless" name="XCont2"/>
<variable units="dimensionless" name="XCont1"/>
<variable units="per_second" name="KCont2" initial_value="100"/>
<variable units="per_second" name="KCont3" initial_value="60"/>
<variable units="per_second" name="KCont4" initial_value="25"/>
<variable units="micrometre" public_interface="out" name="sarcomere_length" initial_value="2"/>
<variable units="per_micrometre" name="cross_bridge_density" initial_value="0.05"/>
<variable units="dimensionless" name="tension_rest"/>
<variable units="dimensionless" name="tension_active"/>
<variable units="micrometre" name="overlap"/>
<variable units="dimensionless" name="cross_bridge_availability"/>
<variable units="dimensionless" public_interface="out" name="isometric_tension"/>
<variable units="millimolar" public_interface="in" name="Ca_Calmod"/>
<variable units="millimolar" public_interface="in" name="Ca_Trop"/>
<variable units="millimolar" public_interface="in" name="Calmod"/>
<variable units="millimolar" public_interface="in" name="Trop"/>
<variable units="second" public_interface="in" name="time"/>
<math xmlns="http://www.w3.org/1998/Math/MathML">
<apply>
<eq/>
<ci>XCont2</ci>
<apply>
<divide/>
<ci>Ca_Calmod</ci>
<ci>Calmod</ci>
</apply>
</apply>
<apply>
<eq/>
<ci>XCont1</ci>
<apply>
<divide/>
<ci>Ca_Trop</ci>
<ci>Trop</ci>
</apply>
</apply>
<apply>
<eq/>
<apply>
<diff/>
<bvar>
<ci>time</ci>
</bvar>
<ci>light_chain</ci>
</apply>
<apply>
<minus/>
<apply>
<times/>
<ci>KCont1</ci>
<apply>
<power/>
<ci>XCont1</ci>
<cn cellml:units="dimensionless">2</cn>
</apply>
<ci>XCont2</ci>
<apply>
<minus/>
<cn cellml:units="dimensionless">1</cn>
<ci>light_chain</ci>
</apply>
</apply>
<apply>
<times/>
<ci>KCont2</ci>
<ci>light_chain</ci>
</apply>
</apply>
</apply>
<apply>
<eq/>
<apply>
<diff/>
<bvar>
<ci>time</ci>
</bvar>
<ci>cross_bridge</ci>
</apply>
<apply>
<minus/>
<apply>
<times/>
<ci>KCont3</ci>
<ci>light_chain</ci>
<apply>
<minus/>
<cn cellml:units="dimensionless">1</cn>
<ci>cross_bridge</ci>
</apply>
</apply>
<apply>
<times/>
<ci>KCont4</ci>
<ci>cross_bridge</ci>
</apply>
</apply>
</apply>
<apply>
<eq/>
<ci>tension_rest</ci>
<apply>
<times/>
<cn cellml:units="dimensionless">2e-4</cn>
<apply>
<exp/>
<apply>
<times/>
<cn cellml:units="per_micrometre">2</cn>
<ci>sarcomere_length</ci>
</apply>
</apply>
</apply>
</apply>
<apply>
<eq/>
<ci>tension_active</ci>
<piecewise>
<piece>
<apply>
<minus/>
<cn cellml:units="dimensionless">1</cn>
<apply>
<exp/>
<apply>
<times/>
<apply>
<minus/>
<cn cellml:units="per_micrometre">3</cn>
</apply>
<apply>
<minus/>
<ci>sarcomere_length</ci>
<cn cellml:units="micrometre">1</cn>
</apply>
</apply>
</apply>
</apply>
<apply>
<gt/>
<ci>sarcomere_length</ci>
<cn cellml:units="micrometre">1</cn>
</apply>
</piece>
<otherwise>
<cn cellml:units="dimensionless">0</cn>
</otherwise>
</piecewise>
</apply>
<apply>
<eq/>
<ci>overlap</ci>
<piecewise>
<piece>
<apply>
<minus/>
<cn cellml:units="micrometre">1</cn>
<apply>
<times/>
<cn cellml:units="dimensionless">0.625</cn>
<apply>
<minus/>
<ci>sarcomere_length</ci>
<cn cellml:units="micrometre">2</cn>
</apply>
</apply>
</apply>
<apply>
<gt/>
<ci>sarcomere_length</ci>
<cn cellml:units="micrometre">2</cn>
</apply>
</piece>
<otherwise>
<cn cellml:units="micrometre">1</cn>
</otherwise>
</piecewise>
</apply>
<apply>
<eq/>
<ci>cross_bridge_availability</ci>
<apply>
<times/>
<ci>tension_active</ci>
<ci>overlap</ci>
<ci>cross_bridge_density</ci>
</apply>
</apply>
<apply>
<eq/>
<ci>isometric_tension</ci>
<apply>
<plus/>
<apply>
<times/>
<ci>cross_bridge</ci>
<ci>cross_bridge_availability</ci>
</apply>
<ci>tension_rest</ci>
</apply>
</apply>
</math>
</component>
<component name="stretch_current">
<variable units="nanoA" public_interface="out" name="i_stretch"/>
<variable units="nanoA" name="i_Ca_stretch"/>
<variable units="nanoA" name="i_K_stretch"/>
<variable units="nanoA" name="i_Na_stretch"/>
<variable units="nanoA" name="i_An_stretch"/>
<variable units="per_micrometre" name="gama_SAC_SL" initial_value="2.5"/>
<variable units="dimensionless" name="gama_SAC_IT" initial_value="2.5"/>
<variable units="micrometre" name="SLHST" initial_value="2"/>
<variable units="dimensionless" name="ITHST" initial_value="1"/>
<variable units="microS" name="g_Ca_stretch" initial_value="0.01"/>
<variable units="microS" name="g_K_stretch" initial_value="0.01"/>
<variable units="microS" name="g_Na_stretch" initial_value="0.01"/>
<variable units="microS" name="g_An_stretch" initial_value="0.01"/>
<variable units="millivolt" name="E_An_stretch" initial_value="-20"/>
<variable units="dimensionless" name="f_stretch"/>
<variable units="dimensionless" public_interface="in" name="isometric_tension"/>
<variable units="micrometre" public_interface="in" name="sarcomere_length"/>
<variable units="millivolt" public_interface="in" name="E_Ca"/>
<variable units="millivolt" public_interface="in" name="E_K"/>
<variable units="millivolt" public_interface="in" name="E_Na"/>
<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>f_stretch</ci>
<piecewise>
<piece>
<apply>
<divide/>
<cn cellml:units="dimensionless">1</cn>
<apply>
<plus/>
<cn cellml:units="dimensionless">1</cn>
<apply>
<exp/>
<apply>
<times/>
<apply>
<minus/>
<cn cellml:units="dimensionless">2</cn>
</apply>
<ci>gama_SAC_IT</ci>
<apply>
<minus/>
<ci>isometric_tension</ci>
<ci>ITHST</ci>
</apply>
</apply>
</apply>
</apply>
</apply>
<apply>
<gt/>
<ci>isometric_tension</ci>
<cn cellml:units="dimensionless">0</cn>
</apply>
</piece>
<otherwise>
<apply>
<divide/>
<cn cellml:units="dimensionless">1</cn>
<apply>
<plus/>
<cn cellml:units="dimensionless">1</cn>
<apply>
<exp/>
<apply>
<times/>
<apply>
<minus/>
<cn cellml:units="dimensionless">2</cn>
</apply>
<ci>gama_SAC_SL</ci>
<apply>
<minus/>
<ci>sarcomere_length</ci>
<ci>SLHST</ci>
</apply>
</apply>
</apply>
</apply>
</apply>
</otherwise>
</piecewise>
</apply>
<apply>
<eq/>
<ci>i_Ca_stretch</ci>
<apply>
<times/>
<ci>g_Ca_stretch</ci>
<ci>f_stretch</ci>
<apply>
<minus/>
<ci>V</ci>
<ci>E_Ca</ci>
</apply>
</apply>
</apply>
<apply>
<eq/>
<ci>i_Na_stretch</ci>
<apply>
<times/>
<ci>g_Na_stretch</ci>
<ci>f_stretch</ci>
<apply>
<minus/>
<ci>V</ci>
<ci>E_Na</ci>
</apply>
</apply>
</apply>
<apply>
<eq/>
<ci>i_K_stretch</ci>
<apply>
<times/>
<ci>g_K_stretch</ci>
<ci>f_stretch</ci>
<apply>
<minus/>
<ci>V</ci>
<ci>E_K</ci>
</apply>
</apply>
</apply>
<apply>
<eq/>
<ci>i_An_stretch</ci>
<apply>
<times/>
<ci>g_An_stretch</ci>
<ci>f_stretch</ci>
<apply>
<minus/>
<ci>V</ci>
<ci>E_An_stretch</ci>
</apply>
</apply>
</apply>
<apply>
<eq/>
<ci>i_stretch</ci>
<apply>
<plus/>
<ci>i_Ca_stretch</ci>
<ci>i_Na_stretch</ci>
<ci>i_K_stretch</ci>
<ci>i_An_stretch</ci>
</apply>
</apply>
</math>
</component>
<component name="fibroblast">
<variable units="microS" name="g_fibro_junct" initial_value="2.9e-4"/>
<variable units="microS" name="g_fibro" initial_value="2e-4"/>
<variable units="microF" name="c_fibro" initial_value="1e-5"/>
<variable units="microS" name="g_fibro_stretch" initial_value="0"/>
<variable units="millivolt" name="E_fibro_stretch" initial_value="0"/>
<variable units="millivolt" name="V_fibro" initial_value="-20"/>
<variable units="nanoA" name="i_fibro"/>
<variable units="nanoA" name="i_fibro_junct"/>
<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_fibro</ci>
<apply>
<plus/>
<apply>
<times/>
<ci>g_fibro</ci>
<apply>
<plus/>
<ci>V_fibro</ci>
<cn cellml:units="millivolt">20</cn>
</apply>
</apply>
<apply>
<times/>
<ci>g_fibro_stretch</ci>
<apply>
<minus/>
<ci>V_fibro</ci>
<ci>E_fibro_stretch</ci>
</apply>
</apply>
</apply>
</apply>
<apply>
<eq/>
<ci>i_fibro_junct</ci>
<apply>
<times/>
<apply>
<minus/>
<ci>g_fibro_junct</ci>
</apply>
<apply>
<minus/>
<ci>V</ci>
<ci>V_fibro</ci>
</apply>
</apply>
</apply>
<apply>
<eq/>
<apply>
<diff/>
<bvar>
<ci>time</ci>
</bvar>
<ci>V_fibro</ci>
</apply>
<apply>
<divide/>
<apply>
<minus/>
<apply>
<plus/>
<ci>i_fibro</ci>
<ci>i_fibro_junct</ci>
</apply>
</apply>
<ci>c_fibro</ci>
</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="ATP_dependent_potassium_current"/>
<component_ref component="sodium_activated_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="ACh_dependent_potassium_current">
<component_ref component="ACh_dependent_potassium_current_xACh_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 component="contraction"/>
<component_ref component="stretch_current"/>
<component_ref component="fibroblast"/>
</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>
<component_ref component="ACh_dependent_potassium_current">
<component_ref component="ACh_dependent_potassium_current_xACh_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="ATP_dependent_potassium_current"/>
<map_variables variable_2="time" variable_1="time"/>
</connection>
<connection>
<map_components component_2="environment" component_1="ACh_dependent_potassium_current"/>
<map_variables variable_2="time" variable_1="time"/>
</connection>
<connection>
<map_components component_2="environment" component_1="sodium_activated_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>
<map_components component_2="environment" component_1="transient_outward_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="sodium_calcium_exchanger"/>
<map_variables variable_2="time" variable_1="time"/>
</connection>
<connection>
<map_components component_2="environment" component_1="intracellular_sodium_concentration"/>
<map_variables variable_2="time" variable_1="time"/>
</connection>
<connection>
<map_components component_2="environment" component_1="intracellular_potassium_concentration"/>
<map_variables variable_2="time" variable_1="time"/>
</connection>
<connection>
<map_components component_2="environment" component_1="intracellular_calcium_concentration"/>
<map_variables variable_2="time" variable_1="time"/>
</connection>
<connection>
<map_components component_2="environment" component_1="sarcoplasmic_reticulum_calcium_pump"/>
<map_variables variable_2="time" variable_1="time"/>
</connection>
<connection>
<map_components component_2="environment" component_1="calcium_translocation"/>
<map_variables variable_2="time" variable_1="time"/>
</connection>
<connection>
<map_components component_2="environment" component_1="calcium_release"/>
<map_variables variable_2="time" variable_1="time"/>
</connection>
<connection>
<map_components component_2="environment" component_1="contraction"/>
<map_variables variable_2="time" variable_1="time"/>
</connection>
<connection>
<map_components component_2="environment" component_1="stretch_current"/>
<map_variables variable_2="time" variable_1="time"/>
</connection>
<connection>
<map_components component_2="environment" component_1="fibroblast"/>
<map_variables variable_2="time" variable_1="time"/>
</connection>
<connection>
<map_components component_2="membrane" component_1="calcium_release"/>
<map_variables variable_2="V" variable_1="V"/>
</connection>
<connection>
<map_components component_2="reversal_potentials" component_1="membrane"/>
<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="fast_sodium_current" component_1="membrane"/>
<map_variables variable_2="V" variable_1="V"/>
<map_variables variable_2="i_Na" variable_1="i_Na"/>
</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_Ca_cyt" variable_1="i_Ca_L_Ca_cyt"/>
<map_variables variable_2="i_Ca_L_Ca_ds" variable_1="i_Ca_L_Ca_ds"/>
<map_variables variable_2="i_Ca_L_Na_cyt" variable_1="i_Ca_L_Na_cyt"/>
<map_variables variable_2="i_Ca_L_Na_ds" variable_1="i_Ca_L_Na_ds"/>
<map_variables variable_2="i_Ca_L_K_cyt" variable_1="i_Ca_L_K_cyt"/>
<map_variables variable_2="i_Ca_L_K_ds" variable_1="i_Ca_L_K_ds"/>
<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_delayed_rectifier_potassium_current" component_1="membrane"/>
<map_variables variable_2="V" variable_1="V"/>
<map_variables variable_2="i_Kr" variable_1="i_Kr"/>
</connection>
<connection>
<map_components component_2="slow_delayed_rectifier_potassium_current" component_1="membrane"/>
<map_variables variable_2="V" variable_1="V"/>
<map_variables variable_2="i_Ks" variable_1="i_Ks"/>
</connection>
<connection>
<map_components component_2="transient_outward_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="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="sodium_activated_potassium_current" component_1="membrane"/>
<map_variables variable_2="V" variable_1="V"/>
</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"/>
</connection>
<connection>
<map_components component_2="ACh_dependent_potassium_current" component_1="membrane"/>
<map_variables variable_2="V" variable_1="V"/>
<map_variables variable_2="i_K_ACh" variable_1="i_K_ACh"/>
<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="persistent_sodium_current" component_1="membrane"/>
<map_variables variable_2="V" variable_1="V"/>
<map_variables variable_2="i_p_Na" variable_1="i_p_Na"/>
</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_b_Na" variable_1="i_b_Na"/>
</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_b_Ca" variable_1="i_b_Ca"/>
</connection>
<connection>
<map_components component_2="sodium_potassium_pump" component_1="membrane"/>
<map_variables variable_2="i_NaK" variable_1="i_NaK"/>
</connection>
<connection>
<map_components component_2="sodium_calcium_exchanger" component_1="membrane"/>
<map_variables variable_2="V" variable_1="V"/>
<map_variables variable_2="i_NaCa_cyt" variable_1="i_NaCa_cyt"/>
<map_variables variable_2="i_NaCa_ds" variable_1="i_NaCa_ds"/>
<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="stretch_current" component_1="membrane"/>
<map_variables variable_2="V" variable_1="V"/>
<map_variables variable_2="i_stretch" variable_1="i_stretch"/>
</connection>
<connection>
<map_components component_2="fibroblast" component_1="membrane"/>
<map_variables variable_2="V" variable_1="V"/>
</connection>
<connection>
<map_components component_2="intracellular_sodium_concentration" component_1="membrane"/>
<map_variables variable_2="F" variable_1="F"/>
</connection>
<connection>
<map_components component_2="intracellular_potassium_concentration" component_1="membrane"/>
<map_variables variable_2="F" variable_1="F"/>
</connection>
<connection>
<map_components component_2="intracellular_calcium_concentration" component_1="membrane"/>
<map_variables variable_2="F" variable_1="F"/>
</connection>
<connection>
<map_components component_2="sodium_background_current" component_1="reversal_potentials"/>
<map_variables variable_2="E_Na" variable_1="E_Na"/>
</connection>
<connection>
<map_components component_2="persistent_sodium_current" component_1="reversal_potentials"/>
<map_variables variable_2="E_Na" variable_1="E_Na"/>
</connection>
<connection>
<map_components component_2="time_independent_potassium_current" component_1="reversal_potentials"/>
<map_variables variable_2="E_K" variable_1="E_K"/>
</connection>
<connection>
<map_components component_2="rapid_delayed_rectifier_potassium_current" component_1="reversal_potentials"/>
<map_variables variable_2="E_K" variable_1="E_K"/>
</connection>
<connection>
<map_components component_2="slow_delayed_rectifier_potassium_current" component_1="reversal_potentials"/>
<map_variables variable_2="E_Ks" variable_1="E_Ks"/>
</connection>
<connection>
<map_components component_2="sodium_activated_potassium_current" component_1="reversal_potentials"/>
<map_variables variable_2="E_K" variable_1="E_K"/>
</connection>
<connection>
<map_components component_2="transient_outward_current" component_1="reversal_potentials"/>
<map_variables variable_2="E_K" variable_1="E_K"/>
</connection>
<connection>
<map_components component_2="ACh_dependent_potassium_current" component_1="reversal_potentials"/>
<map_variables variable_2="E_K" variable_1="E_K"/>
</connection>
<connection>
<map_components component_2="calcium_background_current" component_1="reversal_potentials"/>
<map_variables variable_2="E_Ca" variable_1="E_Ca"/>
</connection>
<connection>
<map_components component_2="fast_sodium_current" component_1="reversal_potentials"/>
<map_variables variable_2="E_mh" variable_1="E_mh"/>
</connection>
<connection>
<map_components component_2="extracellular_potassium_concentration" component_1="reversal_potentials"/>
<map_variables variable_2="K_o" variable_1="K_o"/>
</connection>
<connection>
<map_components component_2="extracellular_sodium_concentration" component_1="reversal_potentials"/>
<map_variables variable_2="Na_o" variable_1="Na_o"/>
</connection>
<connection>
<map_components component_2="intracellular_potassium_concentration" component_1="reversal_potentials"/>
<map_variables variable_2="K_i" variable_1="K_i"/>
</connection>
<connection>
<map_components component_2="intracellular_sodium_concentration" component_1="reversal_potentials"/>
<map_variables variable_2="Na_i" variable_1="Na_i"/>
</connection>
<connection>
<map_components component_2="extracellular_calcium_concentration" component_1="reversal_potentials"/>
<map_variables variable_2="Ca_o" variable_1="Ca_o"/>
</connection>
<connection>
<map_components component_2="intracellular_calcium_concentration" component_1="reversal_potentials"/>
<map_variables variable_2="Ca_i" variable_1="Ca_i"/>
</connection>
<connection>
<map_components component_2="stretch_current" component_1="reversal_potentials"/>
<map_variables variable_2="E_Ca" variable_1="E_Ca"/>
<map_variables variable_2="E_K" variable_1="E_K"/>
<map_variables variable_2="E_Na" variable_1="E_Na"/>
</connection>
<connection>
<map_components component_2="extracellular_potassium_concentration" component_1="time_independent_potassium_current"/>
<map_variables variable_2="K_o" variable_1="K_o"/>
</connection>
<connection>
<map_components component_2="extracellular_potassium_concentration" component_1="ACh_dependent_potassium_current"/>
<map_variables variable_2="K_o" variable_1="K_o"/>
</connection>
<connection>
<map_components component_2="intracellular_potassium_concentration" component_1="time_independent_potassium_current"/>
<map_variables variable_2="i_K1" variable_1="i_K1"/>
</connection>
<connection>
<map_components component_2="intracellular_potassium_concentration" component_1="rapid_delayed_rectifier_potassium_current"/>
<map_variables variable_2="i_Kr" variable_1="i_Kr"/>
</connection>
<connection>
<map_components component_2="intracellular_potassium_concentration" component_1="slow_delayed_rectifier_potassium_current"/>
<map_variables variable_2="i_Ks" variable_1="i_Ks"/>
</connection>
<connection>
<map_components component_2="intracellular_sodium_concentration" component_1="fast_sodium_current"/>
<map_variables variable_2="i_Na" variable_1="i_Na"/>
</connection>
<connection>
<map_components component_2="intracellular_sodium_concentration" component_1="sodium_background_current"/>
<map_variables variable_2="i_b_Na" variable_1="i_b_Na"/>
<map_variables variable_2="Na_i" variable_1="Na_i"/>
</connection>
<connection>
<map_components component_2="intracellular_sodium_concentration" component_1="persistent_sodium_current"/>
<map_variables variable_2="i_p_Na" variable_1="i_p_Na"/>
</connection>
<connection>
<map_components component_2="intracellular_sodium_concentration" component_1="L_type_Ca_channel"/>
<map_variables variable_2="i_Ca_L_Na_cyt" variable_1="i_Ca_L_Na_cyt"/>
<map_variables variable_2="i_Ca_L_Na_ds" variable_1="i_Ca_L_Na_ds"/>
<map_variables variable_2="Na_i" variable_1="Na_i"/>
</connection>
<connection>
<map_components component_2="intracellular_calcium_concentration" component_1="L_type_Ca_channel"/>
<map_variables variable_2="i_Ca_L_Ca_cyt" variable_1="i_Ca_L_Ca_cyt"/>
<map_variables variable_2="i_Ca_L_Ca_ds" variable_1="i_Ca_L_Ca_ds"/>
<map_variables variable_2="Ca_i" variable_1="Ca_i"/>
<map_variables variable_2="Ca_ds" variable_1="Ca_ds"/>
</connection>
<connection>
<map_components component_2="intracellular_potassium_concentration" component_1="L_type_Ca_channel"/>
<map_variables variable_2="i_Ca_L_K_cyt" variable_1="i_Ca_L_K_cyt"/>
<map_variables variable_2="i_Ca_L_K_ds" variable_1="i_Ca_L_K_ds"/>
<map_variables variable_2="K_i" variable_1="K_i"/>
</connection>
<connection>
<map_components component_2="extracellular_potassium_concentration" component_1="L_type_Ca_channel"/>
<map_variables variable_2="K_o" variable_1="K_o"/>
</connection>
<connection>
<map_components component_2="extracellular_sodium_concentration" component_1="L_type_Ca_channel"/>
<map_variables variable_2="Na_o" variable_1="Na_o"/>
</connection>
<connection>
<map_components component_2="extracellular_calcium_concentration" component_1="L_type_Ca_channel"/>
<map_variables variable_2="Ca_o" variable_1="Ca_o"/>
</connection>
<connection>
<map_components component_2="intracellular_calcium_concentration" component_1="calcium_background_current"/>
<map_variables variable_2="i_b_Ca" variable_1="i_b_Ca"/>
</connection>
<connection>
<map_components component_2="intracellular_sodium_concentration" component_1="sodium_activated_potassium_current"/>
<map_variables variable_2="Na_i" variable_1="Na_i"/>
</connection>
<connection>
<map_components component_2="intracellular_sodium_concentration" component_1="sodium_potassium_pump"/>
<map_variables variable_2="i_NaK" variable_1="i_NaK"/>
<map_variables variable_2="Na_i" variable_1="Na_i"/>
</connection>
<connection>
<map_components component_2="extracellular_potassium_concentration" component_1="sodium_potassium_pump"/>
<map_variables variable_2="K_o" variable_1="K_o"/>
</connection>
<connection>
<map_components component_2="intracellular_potassium_concentration" component_1="sodium_potassium_pump"/>
<map_variables variable_2="i_NaK" variable_1="i_NaK"/>
</connection>
<connection>
<map_components component_2="intracellular_potassium_concentration" component_1="transient_outward_current"/>
<map_variables variable_2="i_to" variable_1="i_to"/>
</connection>
<connection>
<map_components component_2="intracellular_calcium_concentration" component_1="sodium_calcium_exchanger"/>
<map_variables variable_2="i_NaCa_cyt" variable_1="i_NaCa_cyt"/>
<map_variables variable_2="i_NaCa_ds" variable_1="i_NaCa_ds"/>
<map_variables variable_2="Ca_i" variable_1="Ca_i"/>
<map_variables variable_2="Ca_ds" variable_1="Ca_ds"/>
</connection>
<connection>
<map_components component_2="intracellular_sodium_concentration" component_1="sodium_calcium_exchanger"/>
<map_variables variable_2="i_NaCa_cyt" variable_1="i_NaCa_cyt"/>
<map_variables variable_2="Na_i" variable_1="Na_i"/>
</connection>
<connection>
<map_components component_2="extracellular_sodium_concentration" component_1="sodium_calcium_exchanger"/>
<map_variables variable_2="Na_o" variable_1="Na_o"/>
</connection>
<connection>
<map_components component_2="extracellular_calcium_concentration" component_1="sodium_calcium_exchanger"/>
<map_variables variable_2="Ca_o" variable_1="Ca_o"/>
</connection>
<connection>
<map_components component_2="intracellular_calcium_concentration" component_1="sarcoplasmic_reticulum_calcium_pump"/>
<map_variables variable_2="i_up" variable_1="i_up"/>
<map_variables variable_2="Ca_i" variable_1="Ca_i"/>
<map_variables variable_2="Ca_up" variable_1="Ca_up"/>
</connection>
<connection>
<map_components component_2="intracellular_calcium_concentration" component_1="calcium_translocation"/>
<map_variables variable_2="i_trans" variable_1="i_trans"/>
<map_variables variable_2="Ca_rel" variable_1="Ca_rel"/>
<map_variables variable_2="Ca_up" variable_1="Ca_up"/>
</connection>
<connection>
<map_components component_2="intracellular_calcium_concentration" component_1="calcium_release"/>
<map_variables variable_2="i_rel" variable_1="i_rel"/>
<map_variables variable_2="Ca_rel" variable_1="Ca_rel"/>
<map_variables variable_2="Ca_i" variable_1="Ca_i"/>
<map_variables variable_2="Ca_ds" variable_1="Ca_ds"/>
</connection>
<connection>
<map_components component_2="contraction" component_1="intracellular_calcium_concentration"/>
<map_variables variable_2="Ca_Calmod" variable_1="Ca_Calmod"/>
<map_variables variable_2="Ca_Trop" variable_1="Ca_Trop"/>
<map_variables variable_2="Calmod" variable_1="Calmod"/>
<map_variables variable_2="Trop" variable_1="Trop"/>
<map_variables variable_2="isometric_tension" variable_1="isometric_tension"/>
<map_variables variable_2="sarcomere_length" variable_1="sarcomere_length"/>
</connection>
<connection>
<map_components component_2="contraction" component_1="calcium_release"/>
<map_variables variable_2="isometric_tension" variable_1="isometric_tension"/>
<map_variables variable_2="sarcomere_length" variable_1="sarcomere_length"/>
</connection>
<connection>
<map_components component_2="contraction" component_1="stretch_current"/>
<map_variables variable_2="isometric_tension" variable_1="isometric_tension"/>
<map_variables variable_2="sarcomere_length" variable_1="sarcomere_length"/>
</connection>
<connection>
<map_components component_2="rapid_delayed_rectifier_potassium_current_xr1_gate" component_1="rapid_delayed_rectifier_potassium_current"/>
<map_variables variable_2="xr1" variable_1="xr1"/>
<map_variables variable_2="time" variable_1="time"/>
<map_variables variable_2="V" variable_1="V"/>
</connection>
<connection>
<map_components component_2="rapid_delayed_rectifier_potassium_current_xr2_gate" component_1="rapid_delayed_rectifier_potassium_current"/>
<map_variables variable_2="xr2" variable_1="xr2"/>
<map_variables variable_2="time" variable_1="time"/>
<map_variables variable_2="V" variable_1="V"/>
</connection>
<connection>
<map_components component_2="slow_delayed_rectifier_potassium_current_xs_gate" component_1="slow_delayed_rectifier_potassium_current"/>
<map_variables variable_2="xs" variable_1="xs"/>
<map_variables variable_2="time" variable_1="time"/>
<map_variables variable_2="V" variable_1="V"/>
</connection>
<connection>
<map_components component_2="ACh_dependent_potassium_current_xACh_gate" component_1="ACh_dependent_potassium_current"/>
<map_variables variable_2="x_ACh" variable_1="x_ACh"/>
<map_variables variable_2="time" variable_1="time"/>
</connection>
<connection>
<map_components component_2="fast_sodium_current_m_gate" component_1="fast_sodium_current"/>
<map_variables variable_2="m" variable_1="m"/>
<map_variables variable_2="time" variable_1="time"/>
<map_variables variable_2="V" variable_1="V"/>
</connection>
<connection>
<map_components component_2="fast_sodium_current_h_gate" component_1="fast_sodium_current"/>
<map_variables variable_2="h" variable_1="h"/>
<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_f2_gate" component_1="L_type_Ca_channel"/>
<map_variables variable_2="f2" variable_1="f2"/>
<map_variables variable_2="time" variable_1="time"/>
<map_variables variable_2="V" variable_1="V"/>
<map_variables variable_2="Ca_i" variable_1="Ca_i"/>
<map_variables variable_2="Km_f2" variable_1="Km_f2"/>
</connection>
<connection>
<map_components component_2="L_type_Ca_channel_f2ds_gate" component_1="L_type_Ca_channel"/>
<map_variables variable_2="f2ds" variable_1="f2ds"/>
<map_variables variable_2="time" variable_1="time"/>
<map_variables variable_2="V" variable_1="V"/>
<map_variables variable_2="Ca_ds" variable_1="Ca_ds"/>
<map_variables variable_2="Km_f2ds" variable_1="Km_f2ds"/>
<map_variables variable_2="R_decay" variable_1="R_decay"/>
</connection>
<connection>
<map_components component_2="transient_outward_current_s_gate" component_1="transient_outward_current"/>
<map_variables variable_2="s" variable_1="s"/>
<map_variables variable_2="time" variable_1="time"/>
<map_variables variable_2="V" variable_1="V"/>
</connection>
<connection>
<map_components component_2="transient_outward_current_r_gate" component_1="transient_outward_current"/>
<map_variables variable_2="r" variable_1="r"/>
<map_variables variable_2="time" variable_1="time"/>
<map_variables variable_2="V" variable_1="V"/>
</connection>
<connection>
<map_components component_2="intracellular_calcium_concentration" component_1="intracellular_sodium_concentration"/>
<map_variables variable_2="V_i" variable_1="V_i"/>
</connection>
<connection>
<map_components component_2="intracellular_calcium_concentration" component_1="intracellular_potassium_concentration"/>
<map_variables variable_2="V_i" variable_1="V_i"/>
</connection>
<connection>
<map_components component_2="time_independent_potassium_current" component_1="ACh_dependent_potassium_current"/>
<map_variables variable_2="K_mk1" variable_1="K_mk1"/>
</connection>
<rdf:RDF>
<rdf:Seq rdf:about="rdf:#0ce2c5c0-6262-4a24-917e-1fc336b0cabb">
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<rdf:Description rdf:about="rdf:#72025205-c2ee-46ba-945e-6ad6e24afc85">
<vCard:Given>D</vCard:Given>
<vCard:Family>Noble</vCard:Family>
</rdf:Description>
<rdf:Description rdf:about="rdf:#$hm4db">
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</rdf:Description>
<rdf:Description rdf:about="rdf:#db5ec880-ef58-4c15-8e0d-36bf8e7e497f">
<vCard:Given>Penny</vCard:Given>
<vCard:Family>Noble</vCard:Family>
<vCard:Other>J</vCard:Other>
</rdf:Description>
<rdf:Description rdf:about="rdf:#9c09dc78-7f49-4457-93ed-c7b9955a38c8">
<vCard:Given>A</vCard:Given>
<vCard:Family>Varghese</vCard:Family>
</rdf:Description>
<rdf:Description rdf:about="rdf:#a5f2a5b3-2edd-47c1-8582-1eab7e8f752b">
<vCard:Given>James</vCard:Given>
<vCard:Family>Lawson</vCard:Family>
<vCard:Other>Richard</vCard:Other>
</rdf:Description>
<rdf:Description rdf:about="rdf:#d7beb4e1-8910-4c28-b560-61c8d1d4a814">
<dcterms:W3CDTF>2007-12-04T15:11:55+13:00</dcterms:W3CDTF>
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<rdf:Description rdf:about="rdf:#2ecb01cc-a373-40fa-9501-4aa93ccd5d8a">
<dcterms:modified rdf:resource="rdf:#a96b2bdc-cbd5-4502-ac7c-203b452d742b"/>
<rdf:value>Penny Noble was informed by a community member that INaCads was not included in the dCads/dt ODE and hence the system was out of balance. This has been fixed in version 07. An alteration was also made to the model to remove two differential expressions in the intracellular_calcium concentration component to allow PCEnv 0.2 to run the model.</rdf:value>
<cmeta:modifier rdf:resource="rdf:#dec66365-7c06-4d35-8dfb-28989da96412"/>
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<rdf:Description rdf:about="rdf:#6b5feb3f-e3a7-44d9-ab1c-7874f76bb698">
<vCard:FN>James Lawson</vCard:FN>
</rdf:Description>
<rdf:Description rdf:about="rdf:#f7a88ef0-b25b-4f1b-8c84-925bdd5b9e1c">
<vCard:N rdf:resource="rdf:#16333cab-2375-4624-a3e1-16842ffa5ddc"/>
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<rdf:Description rdf:about="#noble_model_1998_stretch">
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<dc:publisher>Department of Physiology, Anatomy & Genetics, University of Oxford</dc:publisher>
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<dcterms:W3CDTF>2006-05-03T00:00:00+00:00</dcterms:W3CDTF>
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<vCard:Orgname>Oxford University</vCard:Orgname>
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<vCard:Given>James</vCard:Given>
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<vCard:Other>Richard</vCard:Other>
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<dcterms:W3CDTF>2007-07-18T12:59:52+12:00</dcterms:W3CDTF>
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<rdf:value>Note that the missing i_NCX_ds component was added to the dCai/dt rather than the dCads/dt equation in order to achieve balance in the model.</rdf:value>
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<rdf:value>This model has been curated by Penny Noble</rdf:value>
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<dcterms:W3CDTF>2007-09-06T13:01:21+12:00</dcterms:W3CDTF>
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<rdf:value>Units checked, curated.</rdf:value>
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<rdf:value>This version was created by Penny Noble and is known to read into COR. James Lawson fixed an error (19/04/07) that prevented it reading in PCEnv (unsupported predefined operator diff in component intracellular_calcium_concentration. This variant of version 06 is the STRETCH model, which includes acetylcholine dependent modulation and the electromechanical processes simulated by Variant 02, and also includes simulation of stretch and fibroblasts. This model is parameterised the same as the BASIC model, with all additional variables set to zero.
To simulate multiple action potentials with this model the following integrator parameters must be used: max step size must be 0.001 or less, max point density must be 10,000 or more.</rdf:value>
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<rdf:value>Changed stim_end in stimulus protocol from 10.1 to 1,000,000 seconds</rdf:value>
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<dc:title>Canadian Journal of Cardiology</dc:title>
</rdf:Description>
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<dcterms:W3CDTF>2007-06-22T13:59:26+12:00</dcterms:W3CDTF>
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<vCard:Given>Penny</vCard:Given>
<vCard:Family>Noble</vCard:Family>
<vCard:Other>J</vCard:Other>
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<dcterms:W3CDTF>2007-02-06T13:00:00+13:00</dcterms:W3CDTF>
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<rdf:value>Several variables have been given cmeta:id's to allow creation of a PCEnv session file.</rdf:value>
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<rdf:li>diadic space</rdf:li>
<rdf:li>guinea-pig</rdf:li>
<rdf:li>excitation-contraction coupling</rdf:li>
<rdf:li>ventricular myocyte</rdf:li>
<rdf:li>calcium dynamics</rdf:li>
<rdf:li>electrophysiology</rdf:li>
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<rdf:value>This file is a CellML description of Noble, Carghese, Kohl and Noble's 1998 extension of their 1991 guinea pig ventricular cell model. This model incorporates a diadic space, IKr and IKs currents, and length and tension dependent processes. Variant 3 is parameterised for the 'stretch' model.</rdf:value>
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<dcterms:W3CDTF>1998-01-00 00:00</dcterms:W3CDTF>
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<dcterms:W3CDTF>2008-05-14T03:16:52+12:00</dcterms:W3CDTF>
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<vCard:FN>James Lawson</vCard:FN>
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<dc:title>Improved guinea-pig ventricular cell model incorporating a diadic space, IKr and IKs, and length- and tension-dependent processes</dc:title>
<bqs:volume>14(1)</bqs:volume>
<bqs:first_page>123</bqs:first_page>
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