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<title>Na<superscript>+</superscript> Channel Mutation That Causes Both Brugada and Long-QT Syndrome Phenotypes: A Simulation Study of Mechanism</title>
<author>
<firstname>Catherine</firstname>
<surname>Lloyd</surname>
<affiliation>
<shortaffil>Auckland Bioengineering Institute, University of Auckland</shortaffil>
</affiliation>
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<section id="sec_status">
<title>Model Status</title>
<para>
This CellML model represents the wildtype M cell. For more details on the curation status of this model please see this <ulink url="Clancy_Rudy_Mutations.pdf">separate notes document</ulink>.
</para>
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<sect1 id="sec_structure">
<title>Model Structure</title>
<para>
ABSTRACT: BACKGROUND: Complex physiological interactions determine the functional consequences of gene abnormalities and make mechanistic interpretation of phenotypes extremely difficult. A recent example is a single mutation in the C terminus of the cardiac Na(+) channel, 1795insD. The mutation causes two distinct clinical syndromes, long QT (LQT) and Brugada, leading to life-threatening cardiac arrhythmias. Coexistence of these syndromes is seemingly paradoxical; LQT is associated with enhanced Na(+) channel function, and Brugada with reduced function. METHODS AND RESULTS: Using a computational approach, we demonstrate that the 1795insD mutation exerts variable effects depending on the myocardial substrate. We develop Markov models of the wild-type and 1795insD cardiac Na(+) channels. By incorporating the models into a virtual transgenic cell, we elucidate the mechanism by which 1795insD differentially disrupts cellular electrical behavior in epicardial and midmyocardial cell types. We provide a cellular mechanistic basis for the ECG abnormalities observed in patients carrying the 1795insD gene mutation. CONCLUSIONS: We demonstrate that the 1795insD mutation can cause both LQT and Brugada syndromes through interaction with the heterogeneous myocardium in a rate-dependent manner. The results highlight the complexity and multiplicity of genotype-phenotype relationships, and the usefulness of computational approaches in establishing a mechanistic link between genetic defects and functional abnormalities.
</para>
<para>
The original paper reference is cited below:
</para>
<para>
Na<superscript>+</superscript> Channel Mutation That Causes Both Brugada and Long-QT Syndrome Phenotypes: A Simulation Study of Mechanism, Colleen E. Clancy and Yoram Rudy, 2002,
<emphasis>Circulation</emphasis>
, 105, 1208-1213. <ulink url="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=11889015&dopt=Abstract">PubMed ID: 11889015</ulink>
</para>
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<title>cell diagram</title>
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<imagedata fileref="clancy_2002a.png"/>
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<caption>A Markovian model for the wild-type cardiac Na<superscript>+</superscript> channel, embedded within an updated version of the Luo-Rudy dynamic model. C, indicates a closed channel state; IC, a closed-inactivation state; IF, a fast inactivation state; IM, an intermediate inactivation state, and O, an open state.</caption>
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<title>cell diagram2</title>
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<caption>A Markovian model for the mutant 1795insD cardiac Na<superscript>+</superscript> channel, embedded within an updated version of the Luo-Rudy dynamic model. U (upper) indicates background mode of gating; L (lower), represents a small population of bursting channels which fail to inactivate.</caption>
</informalfigure>
</sect1>
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<apply>
<divide/>
<apply>
<minus/>
<apply>
<minus/>
<ci>V</ci>
<cn cellml:units="millivolt">5</cn>
</apply>
</apply>
<cn cellml:units="millivolt">20.3</cn>
</apply>
</apply>
</apply>
</apply>
<apply>
<eq/>
<ci>beta_13</ci>
<apply>
<times/>
<cn cellml:units="per_second">220</cn>
<apply>
<exp/>
<apply>
<divide/>
<apply>
<minus/>
<apply>
<minus/>
<ci>V</ci>
<cn cellml:units="millivolt">10</cn>
</apply>
</apply>
<cn cellml:units="millivolt">20.3</cn>
</apply>
</apply>
</apply>
</apply>
<apply>
<eq/>
<ci>alpha_2</ci>
<apply>
<times/>
<cn cellml:units="per_second">9178</cn>
<apply>
<exp/>
<apply>
<divide/>
<ci>V</ci>
<cn cellml:units="millivolt">29.68</cn>
</apply>
</apply>
</apply>
</apply>
<apply>
<eq/>
<ci>beta_2</ci>
<apply>
<divide/>
<apply>
<times/>
<ci>alpha_13</ci>
<ci>alpha_2</ci>
<ci>alpha_3</ci>
</apply>
<apply>
<times/>
<ci>beta_13</ci>
<ci>beta_3</ci>
</apply>
</apply>
</apply>
<apply>
<eq/>
<ci>alpha_3</ci>
<apply>
<times/>
<cn cellml:units="per_second" type="e-notation">3.7933<sep/>-4</cn>
<apply>
<exp/>
<apply>
<divide/>
<apply>
<minus/>
<ci>V</ci>
</apply>
<cn cellml:units="millivolt">7.7</cn>
</apply>
</apply>
</apply>
</apply>
<apply>
<eq/>
<ci>beta_3</ci>
<apply>
<plus/>
<cn cellml:units="per_second">8.4</cn>
<apply>
<times/>
<cn cellml:units="dimensionless">0.02</cn>
<ci>V</ci>
</apply>
</apply>
</apply>
<apply>
<eq/>
<ci>alpha_4</ci>
<apply>
<divide/>
<ci>alpha_2</ci>
<cn cellml:units="dimensionless">100</cn>
</apply>
</apply>
<apply>
<eq/>
<ci>beta_4</ci>
<ci>alpha_3</ci>
</apply>
<apply>
<eq/>
<ci>alpha_5</ci>
<apply>
<divide/>
<ci>alpha_2</ci>
<cn cellml:units="dimensionless" type="e-notation">9.5<sep/>4</cn>
</apply>
</apply>
<apply>
<eq/>
<ci>beta_5</ci>
<apply>
<divide/>
<ci>alpha_3</ci>
<cn cellml:units="dimensionless">50</cn>
</apply>
</apply>
</math>
</component>
<component name="L_type_Ca_channel">
<variable name="i_Ca_L" public_interface="out" units="microA_per_microF"/>
<variable name="i_CaCa" public_interface="out" units="microA_per_microF"/>
<variable name="i_CaK" public_interface="out" units="microA_per_microF"/>
<variable name="i_CaNa" public_interface="out" units="microA_per_microF"/>
<variable initial_value="0.75" name="gamma_Nai" public_interface="out" units="dimensionless"/>
<variable initial_value="0.75" name="gamma_Nao" public_interface="out" units="dimensionless"/>
<variable initial_value="0.75" name="gamma_Ki" public_interface="out" units="dimensionless"/>
<variable initial_value="0.75" name="gamma_Ko" public_interface="out" units="dimensionless"/>
<variable name="I_CaCa" units="microA_per_microF"/>
<variable name="I_CaK" units="microA_per_microF"/>
<variable name="I_CaNa" units="microA_per_microF"/>
<variable initial_value="0.00054" name="P_Ca" units="cm_per_second"/>
<variable initial_value="6.75e-7" name="P_Na" units="cm_per_second"/>
<variable initial_value="1.93e-7" name="P_K" units="cm_per_second"/>
<variable initial_value="1" name="gamma_Cai" units="dimensionless"/>
<variable initial_value="0.341" name="gamma_Cao" units="dimensionless"/>
<variable name="time" private_interface="out" public_interface="in" units="second"/>
<variable name="V" private_interface="out" public_interface="in" units="millivolt"/>
<variable name="Cai" private_interface="out" public_interface="in" units="millimolar"/>
<variable name="R" public_interface="in" units="joule_per_kilomole_kelvin"/>
<variable name="T" public_interface="in" units="kelvin"/>
<variable name="F" public_interface="in" units="coulomb_per_mole"/>
<variable name="Cao" public_interface="in" units="millimolar"/>
<variable name="Nao" public_interface="in" units="millimolar"/>
<variable name="Ko" public_interface="in" units="millimolar"/>
<variable name="Nai" public_interface="in" units="millimolar"/>
<variable name="Ki" public_interface="in" units="millimolar"/>
<variable name="d" private_interface="in" units="dimensionless"/>
<variable name="f" private_interface="in" units="dimensionless"/>
<variable name="f_Ca" private_interface="in" units="dimensionless"/>
<math xmlns="http://www.w3.org/1998/Math/MathML">
<apply>
<eq/>
<ci>I_CaCa</ci>
<apply>
<divide/>
<apply>
<times/>
<apply>
<divide/>
<apply>
<times/>
<ci>P_Ca</ci>
<apply>
<power/>
<cn cellml:units="dimensionless">2</cn>
<cn cellml:units="dimensionless">2</cn>
</apply>
<ci>V</ci>
<apply>
<power/>
<ci>F</ci>
<cn cellml:units="dimensionless">2</cn>
</apply>
</apply>
<apply>
<times/>
<ci>R</ci>
<ci>T</ci>
</apply>
</apply>
<apply>
<minus/>
<apply>
<times/>
<ci>gamma_Cai</ci>
<ci>Cai</ci>
<apply>
<exp/>
<apply>
<divide/>
<apply>
<times/>
<cn cellml:units="dimensionless">2</cn>
<ci>V</ci>
<ci>F</ci>
</apply>
<apply>
<times/>
<ci>R</ci>
<ci>T</ci>
</apply>
</apply>
</apply>
</apply>
<apply>
<times/>
<ci>gamma_Cao</ci>
<ci>Cao</ci>
</apply>
</apply>
</apply>
<apply>
<minus/>
<apply>
<exp/>
<apply>
<divide/>
<apply>
<times/>
<cn cellml:units="dimensionless">2</cn>
<ci>V</ci>
<ci>F</ci>
</apply>
<apply>
<times/>
<ci>R</ci>
<ci>T</ci>
</apply>
</apply>
</apply>
<cn cellml:units="dimensionless">1</cn>
</apply>
</apply>
</apply>
<apply>
<eq/>
<ci>I_CaNa</ci>
<apply>
<divide/>
<apply>
<times/>
<apply>
<divide/>
<apply>
<times/>
<ci>P_Na</ci>
<apply>
<power/>
<cn cellml:units="dimensionless">1</cn>
<cn cellml:units="dimensionless">2</cn>
</apply>
<ci>V</ci>
<apply>
<power/>
<ci>F</ci>
<cn cellml:units="dimensionless">2</cn>
</apply>
</apply>
<apply>
<times/>
<ci>R</ci>
<ci>T</ci>
</apply>
</apply>
<apply>
<minus/>
<apply>
<times/>
<ci>gamma_Nai</ci>
<ci>Nai</ci>
<apply>
<exp/>
<apply>
<divide/>
<apply>
<times/>
<cn cellml:units="dimensionless">1</cn>
<ci>V</ci>
<ci>F</ci>
</apply>
<apply>
<times/>
<ci>R</ci>
<ci>T</ci>
</apply>
</apply>
</apply>
</apply>
<apply>
<times/>
<ci>gamma_Nao</ci>
<ci>Nao</ci>
</apply>
</apply>
</apply>
<apply>
<minus/>
<apply>
<exp/>
<apply>
<divide/>
<apply>
<times/>
<cn cellml:units="dimensionless">1</cn>
<ci>V</ci>
<ci>F</ci>
</apply>
<apply>
<times/>
<ci>R</ci>
<ci>T</ci>
</apply>
</apply>
</apply>
<cn cellml:units="dimensionless">1</cn>
</apply>
</apply>
</apply>
<apply>
<eq/>
<ci>I_CaK</ci>
<apply>
<divide/>
<apply>
<times/>
<apply>
<divide/>
<apply>
<times/>
<ci>P_K</ci>
<apply>
<power/>
<cn cellml:units="dimensionless">1</cn>
<cn cellml:units="dimensionless">2</cn>
</apply>
<ci>V</ci>
<apply>
<power/>
<ci>F</ci>
<cn cellml:units="dimensionless">2</cn>
</apply>
</apply>
<apply>
<times/>
<ci>R</ci>
<ci>T</ci>
</apply>
</apply>
<apply>
<minus/>
<apply>
<times/>
<ci>gamma_Ki</ci>
<ci>Ki</ci>
<apply>
<exp/>
<apply>
<divide/>
<apply>
<times/>
<cn cellml:units="dimensionless">1</cn>
<ci>V</ci>
<ci>F</ci>
</apply>
<apply>
<times/>
<ci>R</ci>
<ci>T</ci>
</apply>
</apply>
</apply>
</apply>
<apply>
<times/>
<ci>gamma_Ko</ci>
<ci>Ko</ci>
</apply>
</apply>
</apply>
<apply>
<minus/>
<apply>
<exp/>
<apply>
<divide/>
<apply>
<times/>
<cn cellml:units="dimensionless">1</cn>
<ci>V</ci>
<ci>F</ci>
</apply>
<apply>
<times/>
<ci>R</ci>
<ci>T</ci>
</apply>
</apply>
</apply>
<cn cellml:units="dimensionless">1</cn>
</apply>
</apply>
</apply>
<apply>
<eq/>
<ci>i_CaCa</ci>
<apply>
<times/>
<ci>d</ci>
<ci>f</ci>
<ci>f_Ca</ci>
<ci>I_CaCa</ci>
</apply>
</apply>
<apply>
<eq/>
<ci>i_CaNa</ci>
<apply>
<times/>
<ci>d</ci>
<ci>f</ci>
<ci>f_Ca</ci>
<ci>I_CaNa</ci>
</apply>
</apply>
<apply>
<eq/>
<ci>i_CaK</ci>
<apply>
<times/>
<ci>d</ci>
<ci>f</ci>
<ci>f_Ca</ci>
<ci>I_CaK</ci>
</apply>
</apply>
<apply>
<eq/>
<ci>i_Ca_L</ci>
<apply>
<plus/>
<ci>i_CaCa</ci>
<ci>i_CaK</ci>
<ci>i_CaNa</ci>
</apply>
</apply>
</math>
</component>
<component name="L_type_Ca_channel_d_gate">
<variable initial_value="3.176e-6" name="d" public_interface="out" units="dimensionless"/>
<variable name="alpha_d" units="per_second"/>
<variable name="beta_d" units="per_second"/>
<variable name="d_infinity" units="dimensionless"/>
<variable name="tau_d" units="second"/>
<variable name="V" public_interface="in" units="millivolt"/>
<variable name="time" public_interface="in" units="second"/>
<variable name="E0_d" units="millivolt"/>
<math xmlns="http://www.w3.org/1998/Math/MathML">
<apply>
<eq/>
<ci>E0_d</ci>
<apply>
<plus/>
<ci>V</ci>
<cn cellml:units="millivolt">10</cn>
</apply>
</apply>
<apply>
<eq/>
<ci>d_infinity</ci>
<apply>
<divide/>
<cn cellml:units="dimensionless">1</cn>
<apply>
<plus/>
<cn cellml:units="dimensionless">1</cn>
<apply>
<exp/>
<apply>
<divide/>
<apply>
<minus/>
<ci>E0_d</ci>
</apply>
<cn cellml:units="millivolt">6.24</cn>
</apply>
</apply>
</apply>
</apply>
</apply>
<apply>
<eq/>
<ci>tau_d</ci>
<piecewise>
<piece>
<apply>
<divide/>
<cn cellml:units="second">0.001</cn>
<apply>
<times/>
<cn cellml:units="dimensionless">0.035</cn>
<cn cellml:units="dimensionless">6.24</cn>
</apply>
</apply>
<apply>
<lt/>
<apply>
<abs/>
<ci>E0_d</ci>
</apply>
<cn cellml:units="millivolt" type="e-notation">1<sep/>-5</cn>
</apply>
</piece>
<otherwise>
<apply>
<divide/>
<apply>
<times/>
<cn cellml:units="dimensionless">0.001</cn>
<ci>d_infinity</ci>
<apply>
<minus/>
<cn cellml:units="dimensionless">1</cn>
<apply>
<exp/>
<apply>
<divide/>
<apply>
<minus/>
<ci>E0_d</ci>
</apply>
<cn cellml:units="millivolt">6.24</cn>
</apply>
</apply>
</apply>
</apply>
<apply>
<times/>
<cn cellml:units="per_millivolt_second">0.035</cn>
<ci>E0_d</ci>
</apply>
</apply>
</otherwise>
</piecewise>
</apply>
<apply>
<eq/>
<ci>alpha_d</ci>
<apply>
<divide/>
<ci>d_infinity</ci>
<ci>tau_d</ci>
</apply>
</apply>
<apply>
<eq/>
<ci>beta_d</ci>
<apply>
<divide/>
<apply>
<minus/>
<cn cellml:units="dimensionless">1</cn>
<ci>d_infinity</ci>
</apply>
<ci>tau_d</ci>
</apply>
</apply>
<apply>
<eq/>
<apply>
<diff/>
<bvar>
<ci>time</ci>
</bvar>
<ci>d</ci>
</apply>
<apply>
<minus/>
<apply>
<times/>
<ci>alpha_d</ci>
<apply>
<minus/>
<cn cellml:units="dimensionless">1</cn>
<ci>d</ci>
</apply>
</apply>
<apply>
<times/>
<ci>beta_d</ci>
<ci>d</ci>
</apply>
</apply>
</apply>
</math>
</component>
<component name="L_type_Ca_channel_f_gate">
<variable initial_value="0.9998" name="f" public_interface="out" units="dimensionless"/>
<variable name="alpha_f" units="per_second"/>
<variable name="beta_f" units="per_second"/>
<variable name="f_infinity" units="dimensionless"/>
<variable name="tau_f" units="second"/>
<variable name="V" public_interface="in" units="millivolt"/>
<variable name="time" public_interface="in" units="second"/>
<math xmlns="http://www.w3.org/1998/Math/MathML">
<apply>
<eq/>
<ci>f_infinity</ci>
<apply>
<plus/>
<apply>
<divide/>
<cn cellml:units="dimensionless">1</cn>
<apply>
<plus/>
<cn cellml:units="dimensionless">1</cn>
<apply>
<exp/>
<apply>
<divide/>
<apply>
<plus/>
<ci>V</ci>
<cn cellml:units="millivolt">32</cn>
</apply>
<cn cellml:units="millivolt">8</cn>
</apply>
</apply>
</apply>
</apply>
<apply>
<divide/>
<cn cellml:units="dimensionless">0.6</cn>
<apply>
<plus/>
<cn cellml:units="dimensionless">1</cn>
<apply>
<exp/>
<apply>
<divide/>
<apply>
<minus/>
<cn cellml:units="millivolt">50</cn>
<ci>V</ci>
</apply>
<cn cellml:units="millivolt">20</cn>
</apply>
</apply>
</apply>
</apply>
</apply>
</apply>
<apply>
<eq/>
<ci>tau_f</ci>
<apply>
<divide/>
<cn cellml:units="second">0.001</cn>
<apply>
<plus/>
<apply>
<times/>
<cn cellml:units="dimensionless">0.0197</cn>
<apply>
<exp/>
<apply>
<minus/>
<apply>
<power/>
<apply>
<times/>
<cn cellml:units="per_millivolt">0.0337</cn>
<apply>
<plus/>
<ci>V</ci>
<cn cellml:units="millivolt">10</cn>
</apply>
</apply>
<cn cellml:units="dimensionless">2</cn>
</apply>
</apply>
</apply>
</apply>
<cn cellml:units="dimensionless">0.02</cn>
</apply>
</apply>
</apply>
<apply>
<eq/>
<ci>alpha_f</ci>
<apply>
<divide/>
<ci>f_infinity</ci>
<ci>tau_f</ci>
</apply>
</apply>
<apply>
<eq/>
<ci>beta_f</ci>
<apply>
<divide/>
<apply>
<minus/>
<cn cellml:units="dimensionless">1</cn>
<ci>f_infinity</ci>
</apply>
<ci>tau_f</ci>
</apply>
</apply>
<apply>
<eq/>
<apply>
<diff/>
<bvar>
<ci>time</ci>
</bvar>
<ci>f</ci>
</apply>
<apply>
<minus/>
<apply>
<times/>
<ci>alpha_f</ci>
<apply>
<minus/>
<cn cellml:units="dimensionless">1</cn>
<ci>f</ci>
</apply>
</apply>
<apply>
<times/>
<ci>beta_f</ci>
<ci>f</ci>
</apply>
</apply>
</apply>
</math>
</component>
<component name="L_type_Ca_channel_f_Ca_gate">
<variable name="f_Ca" public_interface="out" units="dimensionless"/>
<variable initial_value="0.0006" name="Km_Ca" units="millimolar"/>
<variable name="V" public_interface="in" units="millivolt"/>
<variable name="time" public_interface="in" units="second"/>
<variable name="Cai" public_interface="in" units="millimolar"/>
<math xmlns="http://www.w3.org/1998/Math/MathML">
<apply>
<eq/>
<ci>f_Ca</ci>
<apply>
<divide/>
<cn cellml:units="dimensionless">1</cn>
<apply>
<plus/>
<cn cellml:units="dimensionless">1</cn>
<apply>
<divide/>
<ci>Cai</ci>
<ci>Km_Ca</ci>
</apply>
</apply>
</apply>
</apply>
</math>
</component>
<component name="T_type_Ca_channel">
<variable name="i_Ca_T" public_interface="out" units="microA_per_microF"/>
<variable initial_value="0.05" name="g_CaT" units="milliS_per_microF"/>
<variable name="E_Ca" public_interface="in" units="millivolt"/>
<variable name="time" private_interface="out" public_interface="in" units="second"/>
<variable name="V" private_interface="out" public_interface="in" units="millivolt"/>
<variable name="b" private_interface="in" units="dimensionless"/>
<variable name="g" private_interface="in" units="dimensionless"/>
<math xmlns="http://www.w3.org/1998/Math/MathML">
<apply>
<eq/>
<ci>i_Ca_T</ci>
<apply>
<times/>
<ci>g_CaT</ci>
<ci>b</ci>
<ci>b</ci>
<ci>g</ci>
<apply>
<minus/>
<ci>V</ci>
<ci>E_Ca</ci>
</apply>
</apply>
</apply>
</math>
</component>
<component name="T_type_Ca_channel_b_gate">
<variable initial_value="0.000963" name="b" public_interface="out" units="dimensionless"/>
<variable name="V" public_interface="in" units="millivolt"/>
<variable name="time" public_interface="in" units="second"/>
<variable name="b_inf" units="dimensionless"/>
<variable name="tau_b" units="second"/>
<math xmlns="http://www.w3.org/1998/Math/MathML">
<apply>
<eq/>
<ci>b_inf</ci>
<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">14</cn>
</apply>
</apply>
<cn cellml:units="millivolt">10.8</cn>
</apply>
</apply>
</apply>
</apply>
</apply>
<apply>
<eq/>
<ci>tau_b</ci>
<apply>
<plus/>
<cn cellml:units="second">0.0037</cn>
<apply>
<divide/>
<cn cellml:units="second">0.0061</cn>
<apply>
<plus/>
<cn cellml:units="dimensionless">1</cn>
<apply>
<exp/>
<apply>
<divide/>
<apply>
<plus/>
<ci>V</ci>
<cn cellml:units="millivolt">25</cn>
</apply>
<cn cellml:units="millivolt">4.5</cn>
</apply>
</apply>
</apply>
</apply>
</apply>
</apply>
<apply>
<eq/>
<apply>
<diff/>
<bvar>
<ci>time</ci>
</bvar>
<ci>b</ci>
</apply>
<apply>
<divide/>
<apply>
<minus/>
<ci>b_inf</ci>
<ci>b</ci>
</apply>
<ci>tau_b</ci>
</apply>
</apply>
</math>
</component>
<component name="T_type_Ca_channel_g_gate">
<variable initial_value="0.9944" name="g" public_interface="out" units="dimensionless"/>
<variable name="V" public_interface="in" units="millivolt"/>
<variable name="time" public_interface="in" units="second"/>
<variable name="g_inf" units="dimensionless"/>
<variable name="tau_g" units="second"/>
<math xmlns="http://www.w3.org/1998/Math/MathML">
<apply>
<eq/>
<ci>g_inf</ci>
<apply>
<divide/>
<cn cellml:units="dimensionless">1</cn>
<apply>
<plus/>
<cn cellml:units="dimensionless">1</cn>
<apply>
<exp/>
<apply>
<divide/>
<apply>
<plus/>
<ci>V</ci>
<cn cellml:units="millivolt">60</cn>
</apply>
<cn cellml:units="millivolt">5.6</cn>
</apply>
</apply>
</apply>
</apply>
</apply>
<apply>
<eq/>
<ci>tau_g</ci>
<piecewise>
<piece>
<apply>
<plus/>
<apply>
<times/>
<apply>
<minus/>
<cn cellml:units="second">0.000875</cn>
</apply>
<ci>V</ci>
</apply>
<cn cellml:units="second">0.012</cn>
</apply>
<apply>
<leq/>
<ci>V</ci>
<cn cellml:units="millivolt">0</cn>
</apply>
</piece>
<otherwise>
<cn cellml:units="second">0.012</cn>
</otherwise>
</piecewise>
</apply>
<apply>
<eq/>
<apply>
<diff/>
<bvar>
<ci>time</ci>
</bvar>
<ci>g</ci>
</apply>
<apply>
<divide/>
<apply>
<minus/>
<ci>g_inf</ci>
<ci>g</ci>
</apply>
<ci>tau_g</ci>
</apply>
</apply>
</math>
</component>
<component name="rapid_delayed_rectifier_potassium_current">
<variable name="i_Kr" public_interface="out" units="microA_per_microF"/>
<variable name="g_Kr" units="milliS_per_microF"/>
<variable name="E_Kr" units="millivolt"/>
<variable name="time" private_interface="out" public_interface="in" units="second"/>
<variable name="V" private_interface="out" public_interface="in" units="millivolt"/>
<variable name="Ko" private_interface="out" public_interface="in" units="millimolar"/>
<variable name="Ki" public_interface="in" units="millimolar"/>
<variable name="R" public_interface="in" units="joule_per_kilomole_kelvin"/>
<variable name="T" public_interface="in" units="kelvin"/>
<variable name="F" public_interface="in" units="coulomb_per_mole"/>
<variable name="P_O" private_interface="in" units="dimensionless"/>
<math xmlns="http://www.w3.org/1998/Math/MathML">
<apply>
<eq/>
<ci>i_Kr</ci>
<apply>
<times/>
<ci>g_Kr</ci>
<ci>P_O</ci>
<apply>
<minus/>
<ci>V</ci>
<ci>E_Kr</ci>
</apply>
</apply>
</apply>
<apply>
<eq/>
<ci>g_Kr</ci>
<apply>
<times/>
<cn cellml:units="milliS_per_microF">0.0135</cn>
<apply>
<power/>
<ci>Ko</ci>
<cn cellml:units="dimensionless">0.59</cn>
</apply>
</apply>
</apply>
<apply>
<eq/>
<ci>E_Kr</ci>
<apply>
<times/>
<apply>
<divide/>
<apply>
<times/>
<ci>R</ci>
<ci>T</ci>
</apply>
<ci>F</ci>
</apply>
<apply>
<ln/>
<apply>
<divide/>
<ci>Ko</ci>
<ci>Ki</ci>
</apply>
</apply>
</apply>
</apply>
</math>
</component>
<component name="Kr_channel_states">
<variable initial_value="1.064e-10" name="P_O" public_interface="out" units="dimensionless"/>
<variable initial_value="3.341e-8" name="P_C1" units="dimensionless"/>
<variable initial_value="1.657e-8" name="P_C2" units="dimensionless"/>
<variable initial_value="4.95e-6" name="P_C3" units="dimensionless"/>
<variable initial_value="3.246e-11" name="P_I" units="dimensionless"/>
<variable name="alpha" units="per_second"/>
<variable name="beta" units="per_second"/>
<variable initial_value="2172" name="alpha_in" units="per_second"/>
<variable initial_value="1077" name="beta_in" units="per_second"/>
<variable name="alpha_alpha" units="per_second"/>
<variable name="beta_beta" units="per_second"/>
<variable name="alpha_i" units="per_second"/>
<variable name="beta_i" units="per_second"/>
<variable name="mu" units="per_second"/>
<variable name="time" public_interface="in" units="second"/>
<variable name="V" public_interface="in" units="millivolt"/>
<variable name="Ko" public_interface="in" units="millimolar"/>
<math xmlns="http://www.w3.org/1998/Math/MathML">
<apply>
<eq/>
<apply>
<diff/>
<bvar>
<ci>time</ci>
</bvar>
<ci>P_C3</ci>
</apply>
<apply>
<minus/>
<apply>
<times/>
<ci>beta</ci>
<ci>P_C2</ci>
</apply>
<apply>
<times/>
<ci>alpha</ci>
<ci>P_C3</ci>
</apply>
</apply>
</apply>
<apply>
<eq/>
<apply>
<diff/>
<bvar>
<ci>time</ci>
</bvar>
<ci>P_C2</ci>
</apply>
<apply>
<plus/>
<apply>
<times/>
<apply>
<minus/>
<apply>
<plus/>
<ci>beta</ci>
<ci>alpha_in</ci>
</apply>
</apply>
<ci>P_C2</ci>
</apply>
<apply>
<times/>
<ci>alpha</ci>
<ci>P_C3</ci>
</apply>
<apply>
<times/>
<ci>beta_in</ci>
<ci>P_C1</ci>
</apply>
</apply>
</apply>
<apply>
<eq/>
<apply>
<diff/>
<bvar>
<ci>time</ci>
</bvar>
<ci>P_C1</ci>
</apply>
<apply>
<plus/>
<apply>
<times/>
<apply>
<minus/>
<apply>
<plus/>
<ci>beta_in</ci>
<ci>alpha_alpha</ci>
<ci>alpha_alpha</ci>
</apply>
</apply>
<ci>P_C1</ci>
</apply>
<apply>
<times/>
<ci>alpha_in</ci>
<ci>P_C2</ci>
</apply>
<apply>
<times/>
<ci>beta_beta</ci>
<ci>P_O</ci>
</apply>
<apply>
<times/>
<ci>mu</ci>
<ci>P_I</ci>
</apply>
</apply>
</apply>
<apply>
<eq/>
<apply>
<diff/>
<bvar>
<ci>time</ci>
</bvar>
<ci>P_O</ci>
</apply>
<apply>
<plus/>
<apply>
<times/>
<apply>
<minus/>
<apply>
<plus/>
<ci>beta_beta</ci>
<ci>beta_i</ci>
</apply>
</apply>
<ci>P_O</ci>
</apply>
<apply>
<times/>
<ci>alpha_alpha</ci>
<ci>P_C1</ci>
</apply>
<apply>
<times/>
<ci>alpha_i</ci>
<ci>P_I</ci>
</apply>
</apply>
</apply>
<apply>
<eq/>
<apply>
<diff/>
<bvar>
<ci>time</ci>
</bvar>
<ci>P_I</ci>
</apply>
<apply>
<plus/>
<apply>
<times/>
<apply>
<minus/>
<apply>
<plus/>
<ci>mu</ci>
<ci>alpha_i</ci>
</apply>
</apply>
<ci>P_I</ci>
</apply>
<apply>
<times/>
<ci>alpha_alpha</ci>
<ci>P_C1</ci>
</apply>
<apply>
<times/>
<ci>beta_i</ci>
<ci>P_O</ci>
</apply>
</apply>
</apply>
<apply>
<eq/>
<ci>alpha</ci>
<apply>
<times/>
<cn cellml:units="per_second">55.5</cn>
<apply>
<exp/>
<apply>
<times/>
<cn cellml:units="dimensionless">0.05547153</cn>
<apply>
<minus/>
<ci>V</ci>
<cn cellml:units="millivolt">12</cn>
</apply>
</apply>
</apply>
</apply>
</apply>
<apply>
<eq/>
<ci>beta</ci>
<apply>
<times/>
<cn cellml:units="per_second">2.357</cn>
<apply>
<exp/>
<apply>
<times/>
<apply>
<minus/>
<cn cellml:units="dimensionless">0.036588</cn>
</apply>
<ci>V</ci>
</apply>
</apply>
</apply>
</apply>
<apply>
<eq/>
<ci>alpha_alpha</ci>
<apply>
<times/>
<cn cellml:units="per_second">65.5</cn>
<apply>
<exp/>
<apply>
<times/>
<cn cellml:units="dimensionless">0.05547153</cn>
<apply>
<minus/>
<ci>V</ci>
<cn cellml:units="millivolt">36</cn>
</apply>
</apply>
</apply>
</apply>
</apply>
<apply>
<eq/>
<ci>beta_beta</ci>
<apply>
<times/>
<cn cellml:units="per_second">2.9357</cn>
<apply>
<exp/>
<apply>
<times/>
<apply>
<minus/>
<cn cellml:units="dimensionless">0.02158</cn>
</apply>
<ci>V</ci>
</apply>
</apply>
</apply>
</apply>
<apply>
<eq/>
<ci>alpha_i</ci>
<apply>
<divide/>
<apply>
<times/>
<cn cellml:units="per_second">439</cn>
<apply>
<exp/>
<apply>
<times/>
<apply>
<minus/>
<cn cellml:units="dimensionless">0.02352</cn>
</apply>
<apply>
<plus/>
<ci>V</ci>
<cn cellml:units="millivolt">25</cn>
</apply>
</apply>
</apply>
<cn cellml:units="millimolar">4.5</cn>
</apply>
<ci>Ko</ci>
</apply>
</apply>
<apply>
<eq/>
<ci>beta_i</ci>
<apply>
<divide/>
<apply>
<times/>
<cn cellml:units="per_second">656</cn>
<apply>
<exp/>
<apply>
<times/>
<cn cellml:units="dimensionless">0.000942</cn>
<ci>V</ci>
</apply>
</apply>
<apply>
<power/>
<cn cellml:units="millimolar">4.5</cn>
<cn cellml:units="dimensionless">0.3</cn>
</apply>
</apply>
<apply>
<power/>
<ci>Ko</ci>
<cn cellml:units="dimensionless">0.3</cn>
</apply>
</apply>
</apply>
<apply>
<eq/>
<ci>mu</ci>
<apply>
<divide/>
<apply>
<times/>
<ci>alpha_i</ci>
<ci>beta_beta</ci>
<ci>alpha_alpha</ci>
</apply>
<apply>
<times/>
<ci>alpha_alpha</ci>
<ci>beta_i</ci>
</apply>
</apply>
</apply>
</math>
</component>
<component name="slow_delayed_rectifier_potassium_current">
<variable name="i_Ks" public_interface="out" units="microA_per_microF"/>
<variable name="g_Ks" units="milliS_per_microF"/>
<variable name="E_Ks" units="millivolt"/>
<variable initial_value="0.01833" name="PNaK" units="dimensionless"/>
<variable name="time" private_interface="out" public_interface="in" units="second"/>
<variable name="V" private_interface="out" public_interface="in" units="millivolt"/>
<variable name="R" public_interface="in" units="joule_per_kilomole_kelvin"/>
<variable name="T" public_interface="in" units="kelvin"/>
<variable name="F" public_interface="in" units="coulomb_per_mole"/>
<variable name="Ko" public_interface="in" units="millimolar"/>
<variable name="Ki" public_interface="in" units="millimolar"/>
<variable name="Nao" public_interface="in" units="millimolar"/>
<variable name="Nai" public_interface="in" units="millimolar"/>
<variable name="Cai" public_interface="in" units="millimolar"/>
<variable name="xs1" private_interface="in" units="dimensionless"/>
<variable name="xs2" private_interface="in" units="dimensionless"/>
<math xmlns="http://www.w3.org/1998/Math/MathML">
<apply>
<eq/>
<ci>E_Ks</ci>
<apply>
<times/>
<apply>
<divide/>
<apply>
<times/>
<ci>R</ci>
<ci>T</ci>
</apply>
<ci>F</ci>
</apply>
<apply>
<ln/>
<apply>
<divide/>
<apply>
<plus/>
<ci>Ko</ci>
<apply>
<times/>
<ci>PNaK</ci>
<ci>Nao</ci>
</apply>
</apply>
<apply>
<plus/>
<ci>Ki</ci>
<apply>
<times/>
<ci>PNaK</ci>
<ci>Nai</ci>
</apply>
</apply>
</apply>
</apply>
</apply>
</apply>
<apply>
<eq/>
<ci>g_Ks</ci>
<apply>
<times/>
<cn cellml:units="dimensionless">0.866</cn>
<cn cellml:units="milliS_per_cm2">0.433</cn>
<apply>
<plus/>
<cn cellml:units="dimensionless">1</cn>
<apply>
<divide/>
<cn cellml:units="dimensionless">0.6</cn>
<apply>
<plus/>
<cn cellml:units="dimensionless">1</cn>
<apply>
<power/>
<apply>
<divide/>
<cn cellml:units="millimolar" type="e-notation">3.8<sep/>-5</cn>
<ci>Cai</ci>
</apply>
<cn cellml:units="dimensionless">1.4</cn>
</apply>
</apply>
</apply>
</apply>
</apply>
</apply>
<apply>
<eq/>
<ci>i_Ks</ci>
<apply>
<times/>
<ci>g_Ks</ci>
<ci>xs1</ci>
<ci>xs2</ci>
<apply>
<minus/>
<ci>V</ci>
<ci>E_Ks</ci>
</apply>
</apply>
</apply>
</math>
</component>
<component name="slow_delayed_rectifier_potassium_current_xs1_gate">
<variable initial_value="0.00441" name="xs1" public_interface="out" units="dimensionless"/>
<variable name="xs1_infinity" units="dimensionless"/>
<variable name="tau_xs1" units="second"/>
<variable name="V" public_interface="in" units="millivolt"/>
<variable name="time" public_interface="in" units="second"/>
<math xmlns="http://www.w3.org/1998/Math/MathML">
<apply>
<eq/>
<ci>xs1_infinity</ci>
<apply>
<divide/>
<cn cellml:units="dimensionless">1</cn>
<apply>
<plus/>
<cn cellml:units="dimensionless">1</cn>
<apply>
<exp/>
<apply>
<divide/>
<apply>
<minus/>
<apply>
<minus/>
<ci>V</ci>
<cn cellml:units="millivolt">1.5</cn>
</apply>
</apply>
<cn cellml:units="millivolt">16.7</cn>
</apply>
</apply>
</apply>
</apply>
</apply>
<apply>
<eq/>
<ci>tau_xs1</ci>
<apply>
<divide/>
<cn cellml:units="second">0.001</cn>
<apply>
<plus/>
<apply>
<divide/>
<apply>
<times/>
<cn cellml:units="dimensionless" type="e-notation">7.19<sep/>-5</cn>
<apply>
<plus/>
<ci>V</ci>
<cn cellml:units="millivolt">30</cn>
</apply>
</apply>
<apply>
<minus/>
<cn cellml:units="dimensionless">1</cn>
<apply>
<exp/>
<apply>
<times/>
<apply>
<minus/>
<cn cellml:units="dimensionless">0.148</cn>
</apply>
<apply>
<plus/>
<ci>V</ci>
<cn cellml:units="millivolt">30</cn>
</apply>
</apply>
</apply>
</apply>
</apply>
<apply>
<divide/>
<apply>
<times/>
<cn cellml:units="dimensionless">0.000131</cn>
<apply>
<plus/>
<ci>V</ci>
<cn cellml:units="millivolt">30</cn>
</apply>
</apply>
<apply>
<minus/>
<apply>
<exp/>
<apply>
<times/>
<cn cellml:units="dimensionless">0.0687</cn>
<apply>
<plus/>
<ci>V</ci>
<cn cellml:units="millivolt">30</cn>
</apply>
</apply>
</apply>
<cn cellml:units="dimensionless">1</cn>
</apply>
</apply>
</apply>
</apply>
</apply>
<apply>
<eq/>
<apply>
<diff/>
<bvar>
<ci>time</ci>
</bvar>
<ci>xs1</ci>
</apply>
<apply>
<divide/>
<apply>
<minus/>
<ci>xs1_infinity</ci>
<ci>xs1</ci>
</apply>
<ci>tau_xs1</ci>
</apply>
</apply>
</math>
</component>
<component name="slow_delayed_rectifier_potassium_current_xs2_gate">
<variable initial_value="0.00441" name="xs2" public_interface="out" units="dimensionless"/>
<variable name="xs2_infinity" units="dimensionless"/>
<variable name="tau_xs2" units="second"/>
<variable name="V" public_interface="in" units="millivolt"/>
<variable name="time" public_interface="in" units="second"/>
<math xmlns="http://www.w3.org/1998/Math/MathML">
<apply>
<eq/>
<ci>xs2_infinity</ci>
<apply>
<divide/>
<cn cellml:units="dimensionless">1</cn>
<apply>
<plus/>
<cn cellml:units="dimensionless">1</cn>
<apply>
<exp/>
<apply>
<divide/>
<apply>
<minus/>
<apply>
<minus/>
<ci>V</ci>
<cn cellml:units="millivolt">1.5</cn>
</apply>
</apply>
<cn cellml:units="millivolt">16.7</cn>
</apply>
</apply>
</apply>
</apply>
</apply>
<apply>
<eq/>
<ci>tau_xs2</ci>
<apply>
<divide/>
<apply>
<times/>
<cn cellml:units="dimensionless">4</cn>
<cn cellml:units="second">0.001</cn>
</apply>
<apply>
<plus/>
<apply>
<divide/>
<apply>
<times/>
<cn cellml:units="dimensionless" type="e-notation">7.19<sep/>-5</cn>
<apply>
<plus/>
<ci>V</ci>
<cn cellml:units="millivolt">30</cn>
</apply>
</apply>
<apply>
<minus/>
<cn cellml:units="dimensionless">1</cn>
<apply>
<exp/>
<apply>
<times/>
<apply>
<minus/>
<cn cellml:units="dimensionless">0.148</cn>
</apply>
<apply>
<plus/>
<ci>V</ci>
<cn cellml:units="millivolt">30</cn>
</apply>
</apply>
</apply>
</apply>
</apply>
<apply>
<divide/>
<apply>
<times/>
<cn cellml:units="dimensionless">0.000131</cn>
<apply>
<plus/>
<ci>V</ci>
<cn cellml:units="millivolt">30</cn>
</apply>
</apply>
<apply>
<minus/>
<apply>
<exp/>
<apply>
<times/>
<cn cellml:units="dimensionless">0.0687</cn>
<apply>
<plus/>
<ci>V</ci>
<cn cellml:units="millivolt">30</cn>
</apply>
</apply>
</apply>
<cn cellml:units="dimensionless">1</cn>
</apply>
</apply>
</apply>
</apply>
</apply>
<apply>
<eq/>
<apply>
<diff/>
<bvar>
<ci>time</ci>
</bvar>
<ci>xs2</ci>
</apply>
<apply>
<divide/>
<apply>
<minus/>
<ci>xs2_infinity</ci>
<ci>xs2</ci>
</apply>
<ci>tau_xs2</ci>
</apply>
</apply>
</math>
</component>
<component name="time_independent_potassium_current">
<variable name="i_K1" public_interface="out" units="microA_per_microF"/>
<variable name="E_K" private_interface="out" public_interface="out" units="millivolt"/>
<variable name="g_K1" units="milliS_per_cm2"/>
<variable name="time" private_interface="out" public_interface="in" units="second"/>
<variable name="V" private_interface="out" public_interface="in" units="millivolt"/>
<variable name="Ko" public_interface="in" units="millimolar"/>
<variable name="Ki" public_interface="in" units="millimolar"/>
<variable name="R" public_interface="in" units="joule_per_kilomole_kelvin"/>
<variable name="T" public_interface="in" units="kelvin"/>
<variable name="F" public_interface="in" units="coulomb_per_mole"/>
<variable name="K1_infinity" private_interface="in" units="dimensionless"/>
<math xmlns="http://www.w3.org/1998/Math/MathML">
<apply>
<eq/>
<ci>g_K1</ci>
<apply>
<times/>
<cn cellml:units="milliS_per_microF">0.75</cn>
<apply>
<root/>
<apply>
<divide/>
<ci>Ko</ci>
<cn cellml:units="millimolar">5.4</cn>
</apply>
</apply>
</apply>
</apply>
<apply>
<eq/>
<ci>E_K</ci>
<apply>
<times/>
<apply>
<divide/>
<apply>
<times/>
<ci>R</ci>
<ci>T</ci>
</apply>
<ci>F</ci>
</apply>
<apply>
<ln/>
<apply>
<divide/>
<ci>Ko</ci>
<ci>Ki</ci>
</apply>
</apply>
</apply>
</apply>
<apply>
<eq/>
<ci>i_K1</ci>
<apply>
<times/>
<ci>g_K1</ci>
<ci>K1_infinity</ci>
<apply>
<minus/>
<ci>V</ci>
<ci>E_K</ci>
</apply>
</apply>
</apply>
</math>
</component>
<component name="time_independent_potassium_current_K1_gate">
<variable name="K1_infinity" public_interface="out" units="dimensionless"/>
<variable name="alpha_K1" units="per_second"/>
<variable name="beta_K1" units="per_second"/>
<variable name="V" public_interface="in" units="millivolt"/>
<variable name="time" public_interface="in" units="second"/>
<variable name="E_K" public_interface="in" units="millivolt"/>
<math xmlns="http://www.w3.org/1998/Math/MathML">
<apply>
<eq/>
<ci>alpha_K1</ci>
<apply>
<divide/>
<cn cellml:units="per_second">1020</cn>
<apply>
<plus/>
<cn cellml:units="dimensionless">1</cn>
<apply>
<exp/>
<apply>
<times/>
<cn cellml:units="per_millivolt">0.2385</cn>
<apply>
<minus/>
<apply>
<minus/>
<ci>V</ci>
<ci>E_K</ci>
</apply>
<cn cellml:units="millivolt">59.215</cn>
</apply>
</apply>
</apply>
</apply>
</apply>
</apply>
<apply>
<eq/>
<ci>beta_K1</ci>
<apply>
<divide/>
<apply>
<times/>
<cn cellml:units="dimensionless">1000</cn>
<apply>
<plus/>
<apply>
<times/>
<cn cellml:units="per_second">0.49124</cn>
<apply>
<exp/>
<apply>
<times/>
<cn cellml:units="dimensionless">0.08032</cn>
<apply>
<plus/>
<apply>
<minus/>
<ci>V</ci>
<ci>E_K</ci>
</apply>
<cn cellml:units="millivolt">5.476</cn>
</apply>
</apply>
</apply>
</apply>
<apply>
<exp/>
<apply>
<times/>
<cn cellml:units="dimensionless">0.06175</cn>
<apply>
<minus/>
<apply>
<minus/>
<ci>V</ci>
<ci>E_K</ci>
</apply>
<cn cellml:units="millivolt">594.31</cn>
</apply>
</apply>
</apply>
</apply>
</apply>
<apply>
<plus/>
<cn cellml:units="dimensionless">1</cn>
<apply>
<exp/>
<apply>
<times/>
<apply>
<minus/>
<cn cellml:units="per_millivolt">0.5143</cn>
</apply>
<apply>
<plus/>
<apply>
<minus/>
<ci>V</ci>
<ci>E_K</ci>
</apply>
<cn cellml:units="millivolt">4.753</cn>
</apply>
</apply>
</apply>
</apply>
</apply>
</apply>
<apply>
<eq/>
<ci>K1_infinity</ci>
<apply>
<divide/>
<ci>alpha_K1</ci>
<apply>
<plus/>
<ci>alpha_K1</ci>
<ci>beta_K1</ci>
</apply>
</apply>
</apply>
</math>
</component>
<component name="plateau_potassium_current">
<variable name="i_Kp" public_interface="out" units="microA_per_microF"/>
<variable initial_value="0.00552" name="g_Kp" units="milliS_per_microF"/>
<variable name="Kp" units="dimensionless"/>
<variable name="time" public_interface="in" units="second"/>
<variable name="V" public_interface="in" units="millivolt"/>
<variable name="E_K" public_interface="in" units="millivolt"/>
<math xmlns="http://www.w3.org/1998/Math/MathML">
<apply>
<eq/>
<ci>Kp</ci>
<apply>
<divide/>
<cn cellml:units="dimensionless">1</cn>
<apply>
<plus/>
<cn cellml:units="dimensionless">1</cn>
<apply>
<exp/>
<apply>
<divide/>
<apply>
<minus/>
<cn cellml:units="millivolt">7.488</cn>
<ci>V</ci>
</apply>
<cn cellml:units="millivolt">5.98</cn>
</apply>
</apply>
</apply>
</apply>
</apply>
<apply>
<eq/>
<ci>i_Kp</ci>
<apply>
<times/>
<ci>g_Kp</ci>
<ci>Kp</ci>
<apply>
<minus/>
<ci>V</ci>
<ci>E_K</ci>
</apply>
</apply>
</apply>
</math>
</component>
<component name="sodium_activated_potassium_current">
<variable name="i_K_Na" public_interface="out" units="microA_per_microF"/>
<variable name="g_K_Na" units="milliS_per_microF"/>
<variable initial_value="2.8" name="nKNa" units="dimensionless"/>
<variable name="pona" units="dimensionless"/>
<variable name="pov" units="dimensionless"/>
<variable initial_value="66" name="kdKNa" units="millimolar"/>
<variable name="time" public_interface="in" units="second"/>
<variable name="V" public_interface="in" units="millivolt"/>
<variable name="Nai" public_interface="in" units="millimolar"/>
<variable name="E_K" public_interface="in" units="millivolt"/>
<math xmlns="http://www.w3.org/1998/Math/MathML">
<apply>
<eq/>
<ci>g_K_Na</ci>
<apply>
<times/>
<cn cellml:units="dimensionless">0</cn>
<cn cellml:units="milliS_per_microF">0.12848</cn>
</apply>
</apply>
<apply>
<eq/>
<ci>pona</ci>
<apply>
<divide/>
<cn cellml:units="dimensionless">0.85</cn>
<apply>
<plus/>
<cn cellml:units="dimensionless">1</cn>
<apply>
<power/>
<apply>
<divide/>
<ci>kdKNa</ci>
<ci>Nai</ci>
</apply>
<ci>nKNa</ci>
</apply>
</apply>
</apply>
</apply>
<apply>
<eq/>
<ci>pov</ci>
<apply>
<minus/>
<cn cellml:units="dimensionless">0.8</cn>
<apply>
<divide/>
<cn cellml:units="dimensionless">0.65</cn>
<apply>
<plus/>
<cn cellml:units="dimensionless">1</cn>
<apply>
<exp/>
<apply>
<divide/>
<apply>
<plus/>
<ci>V</ci>
<cn cellml:units="millivolt">125</cn>
</apply>
<cn cellml:units="millivolt">15</cn>
</apply>
</apply>
</apply>
</apply>
</apply>
</apply>
<apply>
<eq/>
<ci>i_K_Na</ci>
<apply>
<times/>
<ci>g_K_Na</ci>
<ci>pona</ci>
<ci>pov</ci>
<apply>
<minus/>
<ci>V</ci>
<ci>E_K</ci>
</apply>
</apply>
</apply>
</math>
</component>
<component name="ATP_sensitive_potassium_current">
<variable name="i_K_ATP" public_interface="out" units="microA_per_microF"/>
<variable name="g_K_ATP" units="milliS_per_microF"/>
<variable initial_value="1" name="i_K_ATP_on" units="dimensionless"/>
<variable initial_value="0.24" name="nATP" units="dimensionless"/>
<variable initial_value="5e-5" name="nicholsarea" units="dimensionless"/>
<variable initial_value="3" name="ATPi" units="millimolar"/>
<variable initial_value="2" name="hATP" units="dimensionless"/>
<variable initial_value="0.00025" name="kATP" units="millimolar"/>
<variable name="pATP" units="dimensionless"/>
<variable name="GKbaraATP" units="milliS_per_microF"/>
<variable name="time" public_interface="in" units="second"/>
<variable name="V" public_interface="in" units="millivolt"/>
<variable name="Ko" public_interface="in" units="millimolar"/>
<variable name="E_K" public_interface="in" units="millivolt"/>
<math xmlns="http://www.w3.org/1998/Math/MathML">
<apply>
<eq/>
<ci>g_K_ATP</ci>
<apply>
<divide/>
<apply>
<times/>
<ci>i_K_ATP_on</ci>
<cn cellml:units="milliS_per_microF">0.000193</cn>
</apply>
<ci>nicholsarea</ci>
</apply>
</apply>
<apply>
<eq/>
<ci>pATP</ci>
<apply>
<divide/>
<cn cellml:units="dimensionless">1</cn>
<apply>
<plus/>
<cn cellml:units="dimensionless">1</cn>
<apply>
<power/>
<apply>
<divide/>
<ci>ATPi</ci>
<ci>kATP</ci>
</apply>
<ci>hATP</ci>
</apply>
</apply>
</apply>
</apply>
<apply>
<eq/>
<ci>GKbaraATP</ci>
<apply>
<times/>
<ci>g_K_ATP</ci>
<ci>pATP</ci>
<apply>
<power/>
<apply>
<divide/>
<ci>Ko</ci>
<cn cellml:units="dimensionless">4</cn>
</apply>
<ci>nATP</ci>
</apply>
</apply>
</apply>
<apply>
<eq/>
<ci>i_K_ATP</ci>
<apply>
<times/>
<ci>GKbaraATP</ci>
<apply>
<minus/>
<ci>V</ci>
<ci>E_K</ci>
</apply>
</apply>
</apply>
</math>
</component>
<component name="transient_outward_current">
<variable name="i_to" public_interface="out" units="microA_per_microF"/>
<variable name="g_to" units="milliS_per_microF"/>
<variable name="E_K" public_interface="in" units="millivolt"/>
<variable name="V" private_interface="out" public_interface="in" units="millivolt"/>
<variable name="time" private_interface="out" public_interface="in" units="second"/>
<variable name="rvdv" units="dimensionless"/>
<variable name="zdv" private_interface="in" units="dimensionless"/>
<variable name="ydv" private_interface="in" units="dimensionless"/>
<math xmlns="http://www.w3.org/1998/Math/MathML">
<apply>
<eq/>
<ci>g_to</ci>
<cn cellml:units="milliS_per_microF">0.5</cn>
</apply>
<apply>
<eq/>
<ci>rvdv</ci>
<apply>
<exp/>
<apply>
<divide/>
<ci>V</ci>
<cn cellml:units="millivolt">100</cn>
</apply>
</apply>
</apply>
<apply>
<eq/>
<ci>i_to</ci>
<apply>
<times/>
<ci>g_to</ci>
<apply>
<power/>
<ci>zdv</ci>
<cn cellml:units="dimensionless">3</cn>
</apply>
<ci>ydv</ci>
<ci>rvdv</ci>
<apply>
<minus/>
<ci>V</ci>
<ci>E_K</ci>
</apply>
</apply>
</apply>
</math>
</component>
<component name="transient_outward_current_zdv_gate">
<variable initial_value="0.01152" name="zdv" public_interface="out" units="dimensionless"/>
<variable name="alpha_zdv" units="per_second"/>
<variable name="beta_zdv" units="per_second"/>
<variable name="tau_zdv" units="second"/>
<variable name="zdv_ss" units="dimensionless"/>
<variable name="V" public_interface="in" units="millivolt"/>
<variable name="time" public_interface="in" units="second"/>
<math xmlns="http://www.w3.org/1998/Math/MathML">
<apply>
<eq/>
<ci>alpha_zdv</ci>
<apply>
<divide/>
<apply>
<times/>
<cn cellml:units="per_second">10000</cn>
<apply>
<exp/>
<apply>
<divide/>
<apply>
<minus/>
<ci>V</ci>
<cn cellml:units="millivolt">40</cn>
</apply>
<cn cellml:units="millivolt">25</cn>
</apply>
</apply>
</apply>
<apply>
<plus/>
<cn cellml:units="dimensionless">1</cn>
<apply>
<exp/>
<apply>
<divide/>
<apply>
<minus/>
<ci>V</ci>
<cn cellml:units="millivolt">40</cn>
</apply>
<cn cellml:units="millivolt">25</cn>
</apply>
</apply>
</apply>
</apply>
</apply>
<apply>
<eq/>
<ci>beta_zdv</ci>
<apply>
<divide/>
<apply>
<times/>
<cn cellml:units="per_second">10000</cn>
<apply>
<exp/>
<apply>
<divide/>
<apply>
<minus/>
<apply>
<plus/>
<ci>V</ci>
<cn cellml:units="millivolt">90</cn>
</apply>
</apply>
<cn cellml:units="millivolt">25</cn>
</apply>
</apply>
</apply>
<apply>
<plus/>
<cn cellml:units="dimensionless">1</cn>
<apply>
<exp/>
<apply>
<divide/>
<apply>
<minus/>
<apply>
<plus/>
<ci>V</ci>
<cn cellml:units="millivolt">90</cn>
</apply>
</apply>
<cn cellml:units="millivolt">25</cn>
</apply>
</apply>
</apply>
</apply>
</apply>
<apply>
<eq/>
<ci>tau_zdv</ci>
<apply>
<divide/>
<cn cellml:units="dimensionless">1</cn>
<apply>
<plus/>
<ci>alpha_zdv</ci>
<ci>beta_zdv</ci>
</apply>
</apply>
</apply>
<apply>
<eq/>
<ci>zdv_ss</ci>
<apply>
<divide/>
<ci>alpha_zdv</ci>
<apply>
<plus/>
<ci>alpha_zdv</ci>
<ci>beta_zdv</ci>
</apply>
</apply>
</apply>
<apply>
<eq/>
<apply>
<diff/>
<bvar>
<ci>time</ci>
</bvar>
<ci>zdv</ci>
</apply>
<apply>
<divide/>
<apply>
<minus/>
<ci>zdv_ss</ci>
<ci>zdv</ci>
</apply>
<ci>tau_zdv</ci>
</apply>
</apply>
</math>
</component>
<component name="transient_outward_current_ydv_gate">
<variable initial_value="0.99998" name="ydv" public_interface="out" units="dimensionless"/>
<variable name="alpha_ydv" units="per_second"/>
<variable name="beta_ydv" units="per_second"/>
<variable name="tau_ydv" units="second"/>
<variable name="ydv_ss" units="dimensionless"/>
<variable name="V" public_interface="in" units="millivolt"/>
<variable name="time" public_interface="in" units="second"/>
<math xmlns="http://www.w3.org/1998/Math/MathML">
<apply>
<eq/>
<ci>alpha_ydv</ci>
<apply>
<divide/>
<cn cellml:units="per_second">15</cn>
<apply>
<plus/>
<cn cellml:units="dimensionless">1</cn>
<apply>
<exp/>
<apply>
<divide/>
<apply>
<plus/>
<ci>V</ci>
<cn cellml:units="millivolt">60</cn>
</apply>
<cn cellml:units="millivolt">5</cn>
</apply>
</apply>
</apply>
</apply>
</apply>
<apply>
<eq/>
<ci>beta_ydv</ci>
<apply>
<divide/>
<apply>
<times/>
<cn cellml:units="per_second">100</cn>
<apply>
<exp/>
<apply>
<divide/>
<apply>
<plus/>
<ci>V</ci>
<cn cellml:units="millivolt">25</cn>
</apply>
<cn cellml:units="millivolt">5</cn>
</apply>
</apply>
</apply>
<apply>
<plus/>
<cn cellml:units="dimensionless">1</cn>
<apply>
<exp/>
<apply>
<divide/>
<apply>
<plus/>
<ci>V</ci>
<cn cellml:units="millivolt">25</cn>
</apply>
<cn cellml:units="millivolt">5</cn>
</apply>
</apply>
</apply>
</apply>
</apply>
<apply>
<eq/>
<ci>tau_ydv</ci>
<apply>
<divide/>
<cn cellml:units="dimensionless">1</cn>
<apply>
<plus/>
<ci>alpha_ydv</ci>
<ci>beta_ydv</ci>
</apply>
</apply>
</apply>
<apply>
<eq/>
<ci>ydv_ss</ci>
<apply>
<divide/>
<ci>alpha_ydv</ci>
<apply>
<plus/>
<ci>alpha_ydv</ci>
<ci>beta_ydv</ci>
</apply>
</apply>
</apply>
<apply>
<eq/>
<apply>
<diff/>
<bvar>
<ci>time</ci>
</bvar>
<ci>ydv</ci>
</apply>
<apply>
<divide/>
<apply>
<minus/>
<ci>ydv_ss</ci>
<ci>ydv</ci>
</apply>
<ci>tau_ydv</ci>
</apply>
</apply>
</math>
</component>
<component name="sarcolemmal_calcium_pump">
<variable name="i_p_Ca" public_interface="out" units="microA_per_microF"/>
<variable initial_value="0.0005" name="K_mpCa" units="millimolar"/>
<variable initial_value="1.15" name="I_pCa" units="microA_per_microF"/>
<variable name="time" public_interface="in" units="second"/>
<variable name="Cai" public_interface="in" units="millimolar"/>
<math xmlns="http://www.w3.org/1998/Math/MathML">
<apply>
<eq/>
<ci>i_p_Ca</ci>
<apply>
<divide/>
<apply>
<times/>
<ci>I_pCa</ci>
<ci>Cai</ci>
</apply>
<apply>
<plus/>
<ci>K_mpCa</ci>
<ci>Cai</ci>
</apply>
</apply>
</apply>
</math>
</component>
<component name="sodium_background_current">
<variable name="i_Na_b" public_interface="out" units="microA_per_microF"/>
<variable initial_value="0.004" name="g_Nab" units="milliS_per_microF"/>
<variable name="time" public_interface="in" units="second"/>
<variable name="V" public_interface="in" units="millivolt"/>
<variable name="E_Na" public_interface="in" units="millivolt"/>
<math xmlns="http://www.w3.org/1998/Math/MathML">
<apply>
<eq/>
<ci>i_Na_b</ci>
<apply>
<times/>
<ci>g_Nab</ci>
<apply>
<minus/>
<ci>V</ci>
<ci>E_Na</ci>
</apply>
</apply>
</apply>
</math>
</component>
<component name="calcium_background_current">
<variable name="i_Ca_b" public_interface="out" units="microA_per_microF"/>
<variable initial_value="0.003016" name="g_Cab" units="milliS_per_microF"/>
<variable name="E_Ca" public_interface="out" units="millivolt"/>
<variable name="time" public_interface="in" units="second"/>
<variable name="V" public_interface="in" units="millivolt"/>
<variable name="R" public_interface="in" units="joule_per_kilomole_kelvin"/>
<variable name="T" public_interface="in" units="kelvin"/>
<variable name="F" public_interface="in" units="coulomb_per_mole"/>
<variable name="Cai" public_interface="in" units="millimolar"/>
<variable name="Cao" public_interface="in" units="millimolar"/>
<math xmlns="http://www.w3.org/1998/Math/MathML">
<apply>
<eq/>
<ci>E_Ca</ci>
<apply>
<times/>
<apply>
<divide/>
<apply>
<times/>
<ci>R</ci>
<ci>T</ci>
</apply>
<apply>
<times/>
<cn cellml:units="dimensionless">2</cn>
<ci>F</ci>
</apply>
</apply>
<apply>
<ln/>
<apply>
<divide/>
<ci>Cao</ci>
<ci>Cai</ci>
</apply>
</apply>
</apply>
</apply>
<apply>
<eq/>
<ci>i_Ca_b</ci>
<apply>
<times/>
<ci>g_Cab</ci>
<apply>
<minus/>
<ci>V</ci>
<ci>E_Ca</ci>
</apply>
</apply>
</apply>
</math>
</component>
<component name="sodium_potassium_pump">
<variable name="i_NaK" public_interface="out" units="microA_per_microF"/>
<variable initial_value="2.25" name="I_NaK" units="microA_per_microF"/>
<variable name="f_NaK" units="dimensionless"/>
<variable initial_value="10" name="K_mNai" units="millimolar"/>
<variable initial_value="1.5" name="K_mKo" units="millimolar"/>
<variable name="sigma" units="dimensionless"/>
<variable name="time" public_interface="in" units="second"/>
<variable name="V" public_interface="in" units="millivolt"/>
<variable name="R" public_interface="in" units="joule_per_kilomole_kelvin"/>
<variable name="T" public_interface="in" units="kelvin"/>
<variable name="F" public_interface="in" units="coulomb_per_mole"/>
<variable name="Nai" public_interface="in" units="millimolar"/>
<variable name="Nao" public_interface="in" units="millimolar"/>
<variable name="Ko" public_interface="in" units="millimolar"/>
<math xmlns="http://www.w3.org/1998/Math/MathML">
<apply>
<eq/>
<ci>sigma</ci>
<apply>
<times/>
<apply>
<divide/>
<cn cellml:units="dimensionless">1</cn>
<cn cellml:units="dimensionless">7</cn>
</apply>
<apply>
<minus/>
<apply>
<exp/>
<apply>
<divide/>
<ci>Nao</ci>
<cn cellml:units="dimensionless">67.3</cn>
</apply>
</apply>
<cn cellml:units="dimensionless">1</cn>
</apply>
</apply>
</apply>
<apply>
<eq/>
<ci>f_NaK</ci>
<apply>
<divide/>
<cn cellml:units="dimensionless">1</cn>
<apply>
<plus/>
<cn cellml:units="dimensionless">1</cn>
<apply>
<times/>
<cn cellml:units="dimensionless">0.1245</cn>
<apply>
<exp/>
<apply>
<divide/>
<apply>
<times/>
<apply>
<minus/>
<cn cellml:units="dimensionless">0.1</cn>
</apply>
<ci>V</ci>
<ci>F</ci>
</apply>
<apply>
<times/>
<ci>R</ci>
<ci>T</ci>
</apply>
</apply>
</apply>
</apply>
<apply>
<times/>
<cn cellml:units="dimensionless">0.0365</cn>
<ci>sigma</ci>
<apply>
<exp/>
<apply>
<divide/>
<apply>
<times/>
<apply>
<minus/>
<ci>V</ci>
</apply>
<ci>F</ci>
</apply>
<apply>
<times/>
<ci>R</ci>
<ci>T</ci>
</apply>
</apply>
</apply>
</apply>
</apply>
</apply>
</apply>
<apply>
<eq/>
<ci>i_NaK</ci>
<apply>
<divide/>
<apply>
<times/>
<apply>
<divide/>
<apply>
<times/>
<ci>I_NaK</ci>
<ci>f_NaK</ci>
<cn cellml:units="dimensionless">1</cn>
</apply>
<apply>
<plus/>
<cn cellml:units="dimensionless">1</cn>
<apply>
<power/>
<apply>
<divide/>
<ci>K_mNai</ci>
<ci>Nai</ci>
</apply>
<cn cellml:units="dimensionless">2</cn>
</apply>
</apply>
</apply>
<ci>Ko</ci>
</apply>
<apply>
<plus/>
<ci>Ko</ci>
<ci>K_mKo</ci>
</apply>
</apply>
</apply>
</math>
</component>
<component name="non_specific_calcium_activated_current">
<variable name="i_ns_Ca" public_interface="out" units="microA_per_microF"/>
<variable name="i_ns_Na" public_interface="out" units="microA_per_microF"/>
<variable name="i_ns_K" public_interface="out" units="microA_per_microF"/>
<variable name="P_ns_Ca" units="cm_per_second"/>
<variable name="gamma_Nai" public_interface="in" units="dimensionless"/>
<variable name="gamma_Nao" public_interface="in" units="dimensionless"/>
<variable name="gamma_Ki" public_interface="in" units="dimensionless"/>
<variable name="gamma_Ko" public_interface="in" units="dimensionless"/>
<variable name="R" public_interface="in" units="joule_per_kilomole_kelvin"/>
<variable name="T" public_interface="in" units="kelvin"/>
<variable name="F" public_interface="in" units="coulomb_per_mole"/>
<variable name="Cao" public_interface="in" units="millimolar"/>
<variable name="Nao" public_interface="in" units="millimolar"/>
<variable name="Ko" public_interface="in" units="millimolar"/>
<variable name="Nai" public_interface="in" units="millimolar"/>
<variable name="Ki" public_interface="in" units="millimolar"/>
<variable name="I_ns_Na" units="microA_per_microF"/>
<variable name="I_ns_K" units="microA_per_microF"/>
<variable initial_value="0.0012" name="K_m_ns_Ca" units="millimolar"/>
<variable name="time" public_interface="in" units="second"/>
<variable name="Cai" public_interface="in" units="millimolar"/>
<variable name="V" public_interface="in" units="millivolt"/>
<math xmlns="http://www.w3.org/1998/Math/MathML">
<apply>
<eq/>
<ci>P_ns_Ca</ci>
<apply>
<times/>
<cn cellml:units="dimensionless">0</cn>
<cn cellml:units="cm_per_second" type="e-notation">1.75<sep/>-7</cn>
</apply>
</apply>
<apply>
<eq/>
<ci>I_ns_Na</ci>
<apply>
<divide/>
<apply>
<times/>
<apply>
<divide/>
<apply>
<times/>
<ci>P_ns_Ca</ci>
<apply>
<power/>
<cn cellml:units="dimensionless">1</cn>
<cn cellml:units="dimensionless">2</cn>
</apply>
<ci>V</ci>
<apply>
<power/>
<ci>F</ci>
<cn cellml:units="dimensionless">2</cn>
</apply>
</apply>
<apply>
<times/>
<ci>R</ci>
<ci>T</ci>
</apply>
</apply>
<apply>
<minus/>
<apply>
<times/>
<ci>gamma_Nai</ci>
<ci>Nai</ci>
<apply>
<exp/>
<apply>
<divide/>
<apply>
<times/>
<cn cellml:units="dimensionless">1</cn>
<ci>V</ci>
<ci>F</ci>
</apply>
<apply>
<times/>
<ci>R</ci>
<ci>T</ci>
</apply>
</apply>
</apply>
</apply>
<apply>
<times/>
<ci>gamma_Nao</ci>
<ci>Nao</ci>
</apply>
</apply>
</apply>
<apply>
<minus/>
<apply>
<exp/>
<apply>
<divide/>
<apply>
<times/>
<cn cellml:units="dimensionless">1</cn>
<ci>V</ci>
<ci>F</ci>
</apply>
<apply>
<times/>
<ci>R</ci>
<ci>T</ci>
</apply>
</apply>
</apply>
<cn cellml:units="dimensionless">1</cn>
</apply>
</apply>
</apply>
<apply>
<eq/>
<ci>I_ns_K</ci>
<apply>
<divide/>
<apply>
<times/>
<apply>
<divide/>
<apply>
<times/>
<ci>P_ns_Ca</ci>
<apply>
<power/>
<cn cellml:units="dimensionless">1</cn>
<cn cellml:units="dimensionless">2</cn>
</apply>
<ci>V</ci>
<apply>
<power/>
<ci>F</ci>
<cn cellml:units="dimensionless">2</cn>
</apply>
</apply>
<apply>
<times/>
<ci>R</ci>
<ci>T</ci>
</apply>
</apply>
<apply>
<minus/>
<apply>
<times/>
<ci>gamma_Ki</ci>
<ci>Ki</ci>
<apply>
<exp/>
<apply>
<divide/>
<apply>
<times/>
<cn cellml:units="dimensionless">1</cn>
<ci>V</ci>
<ci>F</ci>
</apply>
<apply>
<times/>
<ci>R</ci>
<ci>T</ci>
</apply>
</apply>
</apply>
</apply>
<apply>
<times/>
<ci>gamma_Ko</ci>
<ci>Ko</ci>
</apply>
</apply>
</apply>
<apply>
<minus/>
<apply>
<exp/>
<apply>
<divide/>
<apply>
<times/>
<cn cellml:units="dimensionless">1</cn>
<ci>V</ci>
<ci>F</ci>
</apply>
<apply>
<times/>
<ci>R</ci>
<ci>T</ci>
</apply>
</apply>
</apply>
<cn cellml:units="dimensionless">1</cn>
</apply>
</apply>
</apply>
<apply>
<eq/>
<ci>i_ns_Na</ci>
<apply>
<divide/>
<apply>
<times/>
<ci>I_ns_Na</ci>
<cn cellml:units="dimensionless">1</cn>
</apply>
<apply>
<plus/>
<cn cellml:units="dimensionless">1</cn>
<apply>
<power/>
<apply>
<divide/>
<ci>K_m_ns_Ca</ci>
<ci>Cai</ci>
</apply>
<cn cellml:units="dimensionless">3</cn>
</apply>
</apply>
</apply>
</apply>
<apply>
<eq/>
<ci>i_ns_K</ci>
<apply>
<divide/>
<apply>
<times/>
<ci>I_ns_K</ci>
<cn cellml:units="dimensionless">1</cn>
</apply>
<apply>
<plus/>
<cn cellml:units="dimensionless">1</cn>
<apply>
<power/>
<apply>
<divide/>
<ci>K_m_ns_Ca</ci>
<ci>Cai</ci>
</apply>
<cn cellml:units="dimensionless">3</cn>
</apply>
</apply>
</apply>
</apply>
<apply>
<eq/>
<ci>i_ns_Ca</ci>
<apply>
<plus/>
<ci>i_ns_Na</ci>
<ci>i_ns_K</ci>
</apply>
</apply>
</math>
</component>
<component name="Na_Ca_exchanger">
<variable name="i_NaCa" public_interface="out" units="microA_per_microF"/>
<variable initial_value="0.00025" name="c1" units="microA_per_microF"/>
<variable initial_value="0.0001" name="c2" units="millimolar"/>
<variable initial_value="0.15" name="gamma" units="dimensionless"/>
<variable name="time" public_interface="in" units="second"/>
<variable name="V" public_interface="in" units="millivolt"/>
<variable name="R" public_interface="in" units="joule_per_kilomole_kelvin"/>
<variable name="T" public_interface="in" units="kelvin"/>
<variable name="F" public_interface="in" units="coulomb_per_mole"/>
<variable name="Nai" public_interface="in" units="millimolar"/>
<variable name="Nao" public_interface="in" units="millimolar"/>
<variable name="Cai" public_interface="in" units="millimolar"/>
<variable name="Cao" public_interface="in" units="millimolar"/>
<math xmlns="http://www.w3.org/1998/Math/MathML">
<apply>
<eq/>
<ci>i_NaCa</ci>
<apply>
<divide/>
<apply>
<times/>
<ci>c1</ci>
<apply>
<exp/>
<apply>
<divide/>
<apply>
<times/>
<apply>
<minus/>
<ci>gamma</ci>
<cn cellml:units="dimensionless">1</cn>
</apply>
<ci>V</ci>
<ci>F</ci>
</apply>
<apply>
<times/>
<ci>R</ci>
<ci>T</ci>
</apply>
</apply>
</apply>
<apply>
<minus/>
<apply>
<times/>
<apply>
<exp/>
<apply>
<divide/>
<apply>
<times/>
<ci>V</ci>
<ci>F</ci>
</apply>
<apply>
<times/>
<ci>R</ci>
<ci>T</ci>
</apply>
</apply>
</apply>
<apply>
<power/>
<ci>Nai</ci>
<cn cellml:units="dimensionless">3</cn>
</apply>
<ci>Cao</ci>
</apply>
<apply>
<times/>
<apply>
<power/>
<ci>Nao</ci>
<cn cellml:units="dimensionless">3</cn>
</apply>
<ci>Cai</ci>
</apply>
</apply>
</apply>
<apply>
<plus/>
<cn cellml:units="dimensionless">1</cn>
<apply>
<times/>
<ci>c2</ci>
<apply>
<exp/>
<apply>
<divide/>
<apply>
<times/>
<apply>
<minus/>
<ci>gamma</ci>
<cn cellml:units="dimensionless">1</cn>
</apply>
<ci>V</ci>
<ci>F</ci>
</apply>
<apply>
<times/>
<ci>R</ci>
<ci>T</ci>
</apply>
</apply>
</apply>
<apply>
<plus/>
<apply>
<times/>
<apply>
<exp/>
<apply>
<divide/>
<apply>
<times/>
<ci>V</ci>
<ci>F</ci>
</apply>
<apply>
<times/>
<ci>R</ci>
<ci>T</ci>
</apply>
</apply>
</apply>
<apply>
<power/>
<ci>Nai</ci>
<cn cellml:units="dimensionless">3</cn>
</apply>
<ci>Cao</ci>
</apply>
<apply>
<times/>
<apply>
<power/>
<ci>Nao</ci>
<cn cellml:units="dimensionless">3</cn>
</apply>
<ci>Cai</ci>
</apply>
</apply>
</apply>
</apply>
</apply>
</apply>
</math>
</component>
<component name="calcium_dynamics">
<variable name="i_rel" public_interface="out" units="millimolar_per_second"/>
<variable name="i_up" public_interface="out" units="millimolar_per_second"/>
<variable name="i_leak" public_interface="out" units="millimolar_per_second"/>
<variable name="i_tr" public_interface="out" units="millimolar_per_second"/>
<variable name="G_rel" units="per_second"/>
<variable initial_value="60000" name="G_rel_max" units="per_second"/>
<variable initial_value="4000" name="G_rel_overload" units="per_second"/>
<variable initial_value="0.18" name="tau_tr" units="second"/>
<variable initial_value="0.0008" name="K_mrel" units="millimolar"/>
<variable initial_value="0.00018" name="delta_Ca_ith" units="millimolar"/>
<variable initial_value="10" name="CSQN_max" units="millimolar"/>
<variable initial_value="0.8" name="K_mCSQN" units="millimolar"/>
<variable initial_value="0.00092" name="K_mup" units="millimolar"/>
<variable name="K_leak" units="per_second"/>
<variable initial_value="8.75" name="I_up" units="millimolar_per_second"/>
<variable initial_value="15" name="Ca_NSR_max" units="millimolar"/>
<variable name="time" public_interface="in" units="second"/>
<variable name="F" public_interface="in" units="coulomb_per_mole"/>
<variable initial_value="0.000114" name="Cai" public_interface="out" units="millimolar"/>
<variable initial_value="1.8" name="Cao" public_interface="out" units="millimolar"/>
<variable initial_value="1.643" name="Ca_JSR" public_interface="out" units="millimolar"/>
<variable initial_value="1.645" name="Ca_NSR" public_interface="out" units="millimolar"/>
<variable name="V_myo" public_interface="in" units="micro_litre"/>
<variable name="A_cap" public_interface="in" units="mm2"/>
<variable name="V_JSR" units="micro_litre"/>
<variable name="V_NSR" units="micro_litre"/>
<variable name="i_NaCa" public_interface="in" units="microA_per_microF"/>
<variable name="i_CaCa" public_interface="in" units="microA_per_microF"/>
<variable name="i_p_Ca" public_interface="in" units="microA_per_microF"/>
<variable name="i_Ca_b" public_interface="in" units="microA_per_microF"/>
<variable name="i_Ca_T" public_interface="in" units="microA_per_microF"/>
<variable initial_value="0.0005" name="K_mTn" units="millimolar"/>
<variable initial_value="0.00238" name="K_mCMDN" units="millimolar"/>
<variable initial_value="0.07" name="Tn_max" units="millimolar"/>
<variable initial_value="0.05" name="CMDN_max" units="millimolar"/>
<variable name="dVdt" public_interface="in" units="dimensionless"/>
<variable initial_value="0" name="APtrack" units="dimensionless"/>
<variable initial_value="0" name="APtrack2" units="dimensionless"/>
<variable initial_value="0" name="APtrack3" units="dimensionless"/>
<variable initial_value="0" name="Cainfluxtrack" units="dimensionless"/>
<variable initial_value="0" name="OVRLDtrack" units="dimensionless"/>
<variable initial_value="0" name="OVRLDtrack2" units="dimensionless"/>
<variable initial_value="0" name="OVRLDtrack3" units="dimensionless"/>
<variable initial_value="0.7" name="CSQNthresh" units="millimolar"/>
<variable initial_value="0.98" name="Logicthresh" units="dimensionless"/>
<math xmlns="http://www.w3.org/1998/Math/MathML">
<apply>
<eq/>
<ci>V_JSR</ci>
<apply>
<times/>
<apply>
<divide/>
<cn cellml:units="dimensionless">0.0048</cn>
<cn cellml:units="dimensionless">0.68</cn>
</apply>
<ci>V_myo</ci>
</apply>
</apply>
<apply>
<eq/>
<ci>V_NSR</ci>
<apply>
<times/>
<apply>
<divide/>
<cn cellml:units="dimensionless">0.0552</cn>
<cn cellml:units="dimensionless">0.68</cn>
</apply>
<ci>V_myo</ci>
</apply>
</apply>
<apply>
<eq/>
<apply>
<diff/>
<bvar>
<ci>time</ci>
</bvar>
<ci>APtrack</ci>
</apply>
<piecewise>
<piece>
<apply>
<minus/>
<apply>
<times/>
<cn cellml:units="dimensionless">100000</cn>
<apply>
<minus/>
<cn cellml:units="dimensionless">1</cn>
<ci>APtrack</ci>
</apply>
</apply>
<apply>
<times/>
<cn cellml:units="dimensionless">500</cn>
<ci>APtrack</ci>
</apply>
</apply>
<apply>
<gt/>
<ci>dVdt</ci>
<cn cellml:units="dimensionless">150000</cn>
</apply>
</piece>
<otherwise>
<apply>
<times/>
<apply>
<minus/>
<cn cellml:units="dimensionless">500</cn>
</apply>
<ci>APtrack</ci>
</apply>
</otherwise>
</piecewise>
</apply>
<apply>
<eq/>
<apply>
<diff/>
<bvar>
<ci>time</ci>
</bvar>
<ci>APtrack2</ci>
</apply>
<piecewise>
<piece>
<apply>
<minus/>
<apply>
<times/>
<cn cellml:units="dimensionless">100000</cn>
<apply>
<minus/>
<cn cellml:units="dimensionless">1</cn>
<ci>APtrack2</ci>
</apply>
</apply>
<apply>
<times/>
<cn cellml:units="dimensionless">500</cn>
<ci>APtrack2</ci>
</apply>
</apply>
<apply>
<and/>
<apply>
<lt/>
<ci>APtrack</ci>
<cn cellml:units="dimensionless">0.2</cn>
</apply>
<apply>
<gt/>
<ci>APtrack</ci>
<cn cellml:units="dimensionless">0.18</cn>
</apply>
</apply>
</piece>
<otherwise>
<apply>
<times/>
<apply>
<minus/>
<cn cellml:units="dimensionless">500</cn>
</apply>
<ci>APtrack2</ci>
</apply>
</otherwise>
</piecewise>
</apply>
<apply>
<eq/>
<apply>
<diff/>
<bvar>
<ci>time</ci>
</bvar>
<ci>APtrack3</ci>
</apply>
<piecewise>
<piece>
<apply>
<minus/>
<apply>
<times/>
<cn cellml:units="dimensionless">100000</cn>
<apply>
<minus/>
<cn cellml:units="dimensionless">1</cn>
<ci>APtrack3</ci>
</apply>
</apply>
<apply>
<times/>
<cn cellml:units="dimensionless">500</cn>
<ci>APtrack3</ci>
</apply>
</apply>
<apply>
<and/>
<apply>
<lt/>
<ci>APtrack</ci>
<cn cellml:units="dimensionless">0.2</cn>
</apply>
<apply>
<gt/>
<ci>APtrack</ci>
<cn cellml:units="dimensionless">0.18</cn>
</apply>
</apply>
</piece>
<otherwise>
<apply>
<times/>
<apply>
<minus/>
<cn cellml:units="dimensionless">10</cn>
</apply>
<ci>APtrack3</ci>
</apply>
</otherwise>
</piecewise>
</apply>
<apply>
<eq/>
<apply>
<diff/>
<bvar>
<ci>time</ci>
</bvar>
<ci>Cainfluxtrack</ci>
</apply>
<piecewise>
<piece>
<apply>
<divide/>
<apply>
<times/>
<apply>
<minus/>
<ci>A_cap</ci>
</apply>
<apply>
<plus/>
<apply>
<minus/>
<apply>
<plus/>
<ci>i_CaCa</ci>
<ci>i_Ca_T</ci>
</apply>
<ci>i_NaCa</ci>
</apply>
<ci>i_p_Ca</ci>
<ci>i_Ca_b</ci>
</apply>
</apply>
<apply>
<times/>
<cn cellml:units="dimensionless">2</cn>
<ci>V_myo</ci>
<ci>F</ci>
</apply>
</apply>
<apply>
<gt/>
<ci>APtrack</ci>
<cn cellml:units="dimensionless">0.2</cn>
</apply>
</piece>
<piece>
<cn cellml:units="dimensionless">0</cn>
<apply>
<and/>
<apply>
<gt/>
<ci>APtrack2</ci>
<cn cellml:units="dimensionless">0.01</cn>
</apply>
<apply>
<leq/>
<ci>APtrack</ci>
<cn cellml:units="dimensionless">0.2</cn>
</apply>
</apply>
</piece>
<otherwise>
<apply>
<times/>
<apply>
<minus/>
<cn cellml:units="dimensionless">500</cn>
</apply>
<ci>Cainfluxtrack</ci>
</apply>
</otherwise>
</piecewise>
</apply>
<apply>
<eq/>
<apply>
<diff/>
<bvar>
<ci>time</ci>
</bvar>
<ci>OVRLDtrack</ci>
</apply>
<piecewise>
<piece>
<apply>
<times/>
<cn cellml:units="dimensionless">50000</cn>
<apply>
<minus/>
<cn cellml:units="dimensionless">1</cn>
<ci>OVRLDtrack</ci>
</apply>
</apply>
<apply>
<and/>
<apply>
<gt/>
<apply>
<divide/>
<cn cellml:units="dimensionless">1</cn>
<apply>
<plus/>
<cn cellml:units="dimensionless">1</cn>
<apply>
<divide/>
<ci>K_mCSQN</ci>
<ci>Ca_NSR</ci>
</apply>
</apply>
</apply>
<ci>CSQNthresh</ci>
</apply>
<apply>
<lt/>
<ci>OVRLDtrack3</ci>
<cn cellml:units="dimensionless">0.37</cn>
</apply>
<apply>
<lt/>
<ci>APtrack3</ci>
<cn cellml:units="dimensionless">0.37</cn>
</apply>
</apply>
</piece>
<otherwise>
<apply>
<times/>
<apply>
<minus/>
<cn cellml:units="dimensionless">500</cn>
</apply>
<ci>OVRLDtrack</ci>
</apply>
</otherwise>
</piecewise>
</apply>
<apply>
<eq/>
<apply>
<diff/>
<bvar>
<ci>time</ci>
</bvar>
<ci>OVRLDtrack2</ci>
</apply>
<piecewise>
<piece>
<apply>
<times/>
<cn cellml:units="dimensionless">50000</cn>
<apply>
<minus/>
<cn cellml:units="dimensionless">1</cn>
<ci>OVRLDtrack2</ci>
</apply>
</apply>
<apply>
<and/>
<apply>
<gt/>
<ci>OVRLDtrack</ci>
<ci>Logicthresh</ci>
</apply>
<apply>
<lt/>
<ci>OVRLDtrack2</ci>
<ci>Logicthresh</ci>
</apply>
</apply>
</piece>
<otherwise>
<apply>
<times/>
<apply>
<minus/>
<cn cellml:units="dimensionless">500</cn>
</apply>
<ci>OVRLDtrack2</ci>
</apply>
</otherwise>
</piecewise>
</apply>
<apply>
<eq/>
<apply>
<diff/>
<bvar>
<ci>time</ci>
</bvar>
<ci>OVRLDtrack3</ci>
</apply>
<piecewise>
<piece>
<apply>
<times/>
<cn cellml:units="dimensionless">50000</cn>
<apply>
<minus/>
<cn cellml:units="dimensionless">1</cn>
<ci>OVRLDtrack3</ci>
</apply>
</apply>
<apply>
<and/>
<apply>
<gt/>
<ci>OVRLDtrack</ci>
<ci>Logicthresh</ci>
</apply>
<apply>
<lt/>
<ci>OVRLDtrack3</ci>
<ci>Logicthresh</ci>
</apply>
</apply>
</piece>
<otherwise>
<apply>
<times/>
<apply>
<minus/>
<cn cellml:units="dimensionless">10</cn>
</apply>
<ci>OVRLDtrack3</ci>
</apply>
</otherwise>
</piecewise>
</apply>
<apply>
<eq/>
<ci>G_rel</ci>
<piecewise>
<piece>
<apply>
<times/>
<apply>
<divide/>
<apply>
<times/>
<ci>G_rel_max</ci>
<apply>
<minus/>
<ci>Cainfluxtrack</ci>
<ci>delta_Ca_ith</ci>
</apply>
</apply>
<apply>
<minus/>
<apply>
<plus/>
<ci>K_mrel</ci>
<ci>Cainfluxtrack</ci>
</apply>
<ci>delta_Ca_ith</ci>
</apply>
</apply>
<apply>
<minus/>
<cn cellml:units="dimensionless">1</cn>
<ci>APtrack2</ci>
</apply>
<ci>APtrack2</ci>
</apply>
<apply>
<gt/>
<ci>Cainfluxtrack</ci>
<ci>delta_Ca_ith</ci>
</apply>
</piece>
<piece>
<apply>
<times/>
<ci>G_rel_overload</ci>
<apply>
<minus/>
<cn cellml:units="dimensionless">1</cn>
<ci>OVRLDtrack2</ci>
</apply>
<ci>OVRLDtrack2</ci>
</apply>
<apply>
<and/>
<apply>
<leq/>
<ci>Cainfluxtrack</ci>
<ci>delta_Ca_ith</ci>
</apply>
<apply>
<gt/>
<ci>OVRLDtrack2</ci>
<cn cellml:units="dimensionless">0</cn>
</apply>
</apply>
</piece>
<otherwise>
<cn cellml:units="dimensionless">0</cn>
</otherwise>
</piecewise>
</apply>
<apply>
<eq/>
<ci>i_rel</ci>
<apply>
<times/>
<ci>G_rel</ci>
<apply>
<minus/>
<ci>Ca_JSR</ci>
<ci>Cai</ci>
</apply>
</apply>
</apply>
<apply>
<eq/>
<ci>i_up</ci>
<apply>
<divide/>
<apply>
<times/>
<ci>I_up</ci>
<ci>Cai</ci>
</apply>
<apply>
<plus/>
<ci>Cai</ci>
<ci>K_mup</ci>
</apply>
</apply>
</apply>
<apply>
<eq/>
<ci>K_leak</ci>
<apply>
<divide/>
<ci>I_up</ci>
<ci>Ca_NSR_max</ci>
</apply>
</apply>
<apply>
<eq/>
<ci>i_leak</ci>
<apply>
<times/>
<ci>K_leak</ci>
<ci>Ca_NSR</ci>
</apply>
</apply>
<apply>
<eq/>
<ci>i_tr</ci>
<apply>
<divide/>
<apply>
<minus/>
<ci>Ca_NSR</ci>
<ci>Ca_JSR</ci>
</apply>
<ci>tau_tr</ci>
</apply>
</apply>
<apply>
<eq/>
<apply>
<diff/>
<bvar>
<ci>time</ci>
</bvar>
<ci>Ca_JSR</ci>
</apply>
<apply>
<times/>
<apply>
<divide/>
<cn cellml:units="dimensionless">1</cn>
<apply>
<plus/>
<cn cellml:units="dimensionless">1</cn>
<apply>
<divide/>
<apply>
<times/>
<ci>CSQN_max</ci>
<ci>K_mCSQN</ci>
</apply>
<apply>
<power/>
<apply>
<plus/>
<ci>K_mCSQN</ci>
<ci>Ca_JSR</ci>
</apply>
<cn cellml:units="dimensionless">2</cn>
</apply>
</apply>
</apply>
</apply>
<apply>
<minus/>
<ci>i_tr</ci>
<ci>i_rel</ci>
</apply>
</apply>
</apply>
<apply>
<eq/>
<apply>
<diff/>
<bvar>
<ci>time</ci>
</bvar>
<ci>Ca_NSR</ci>
</apply>
<apply>
<plus/>
<apply>
<minus/>
<apply>
<divide/>
<apply>
<times/>
<apply>
<minus/>
<ci>i_tr</ci>
</apply>
<ci>V_JSR</ci>
</apply>
<ci>V_NSR</ci>
</apply>
<ci>i_leak</ci>
</apply>
<ci>i_up</ci>
</apply>
</apply>
<apply>
<eq/>
<apply>
<diff/>
<bvar>
<ci>time</ci>
</bvar>
<ci>Cai</ci>
</apply>
<apply>
<times/>
<apply>
<divide/>
<cn cellml:units="dimensionless">1</cn>
<apply>
<plus/>
<cn cellml:units="dimensionless">1</cn>
<apply>
<divide/>
<apply>
<times/>
<ci>CMDN_max</ci>
<ci>K_mCMDN</ci>
</apply>
<apply>
<power/>
<apply>
<plus/>
<ci>K_mCMDN</ci>
<ci>Cai</ci>
</apply>
<cn cellml:units="dimensionless">2</cn>
</apply>
</apply>
<apply>
<divide/>
<apply>
<times/>
<ci>Tn_max</ci>
<ci>K_mTn</ci>
</apply>
<apply>
<power/>
<apply>
<plus/>
<ci>K_mTn</ci>
<ci>Cai</ci>
</apply>
<cn cellml:units="dimensionless">2</cn>
</apply>
</apply>
</apply>
</apply>
<apply>
<plus/>
<apply>
<divide/>
<apply>
<times/>
<apply>
<minus/>
<ci>A_cap</ci>
</apply>
<apply>
<plus/>
<apply>
<minus/>
<apply>
<plus/>
<ci>i_CaCa</ci>
<ci>i_Ca_T</ci>
</apply>
<apply>
<times/>
<cn cellml:units="dimensionless">2</cn>
<ci>i_NaCa</ci>
</apply>
</apply>
<ci>i_p_Ca</ci>
<ci>i_Ca_b</ci>
</apply>
</apply>
<apply>
<times/>
<cn cellml:units="dimensionless">2</cn>
<ci>V_myo</ci>
<ci>F</ci>
</apply>
</apply>
<apply>
<divide/>
<apply>
<times/>
<ci>i_rel</ci>
<ci>V_JSR</ci>
</apply>
<ci>V_myo</ci>
</apply>
<apply>
<divide/>
<apply>
<times/>
<apply>
<minus/>
<ci>i_leak</ci>
<ci>i_up</ci>
</apply>
<ci>V_NSR</ci>
</apply>
<ci>V_myo</ci>
</apply>
</apply>
</apply>
</apply>
</math>
</component>
<component name="ionic_concentrations">
<variable initial_value="11.544" name="Nai" public_interface="out" units="millimolar"/>
<variable initial_value="132" name="Nao" public_interface="out" units="millimolar"/>
<variable initial_value="140.275" name="Ki" public_interface="out" units="millimolar"/>
<variable initial_value="4.5" name="Ko" public_interface="out" units="millimolar"/>
<variable initial_value="1.434e-7" name="A_cap" public_interface="out" units="mm2"/>
<variable initial_value="0.001" name="preplength" units="mm"/>
<variable initial_value="1.1e-4" name="radius" units="mm"/>
<variable name="volume" units="micro_litre"/>
<variable name="V_myo" public_interface="out" units="micro_litre"/>
<variable name="time" public_interface="in" units="second"/>
<variable name="F" public_interface="in" units="coulomb_per_mole"/>
<variable name="i_Na" public_interface="in" units="microA_per_microF"/>
<variable name="i_CaNa" public_interface="in" units="microA_per_microF"/>
<variable name="i_Na_b" public_interface="in" units="microA_per_microF"/>
<variable name="i_ns_Na" public_interface="in" units="microA_per_microF"/>
<variable name="i_NaCa" public_interface="in" units="microA_per_microF"/>
<variable name="i_NaK" public_interface="in" units="microA_per_microF"/>
<variable name="i_CaK" public_interface="in" units="microA_per_microF"/>
<variable name="i_Kr" public_interface="in" units="microA_per_microF"/>
<variable name="i_Ks" public_interface="in" units="microA_per_microF"/>
<variable name="i_K1" public_interface="in" units="microA_per_microF"/>
<variable name="i_Kp" public_interface="in" units="microA_per_microF"/>
<variable name="i_K_Na" public_interface="in" units="microA_per_microF"/>
<variable name="i_K_ATP" public_interface="in" units="microA_per_microF"/>
<variable name="i_ns_K" public_interface="in" units="microA_per_microF"/>
<variable name="i_to" public_interface="in" units="microA_per_microF"/>
<math xmlns="http://www.w3.org/1998/Math/MathML">
<apply>
<eq/>
<ci>volume</ci>
<apply>
<times/>
<pi/>
<ci>preplength</ci>
<apply>
<power/>
<ci>radius</ci>
<cn cellml:units="dimensionless">2</cn>
</apply>
</apply>
</apply>
<apply>
<eq/>
<ci>V_myo</ci>
<apply>
<times/>
<cn cellml:units="dimensionless">0.68</cn>
<ci>volume</ci>
</apply>
</apply>
<apply>
<eq/>
<apply>
<diff/>
<bvar>
<ci>time</ci>
</bvar>
<ci>Nai</ci>
</apply>
<apply>
<divide/>
<apply>
<times/>
<apply>
<minus/>
<apply>
<plus/>
<ci>i_Na</ci>
<ci>i_CaNa</ci>
<ci>i_Na_b</ci>
<ci>i_ns_Na</ci>
<apply>
<times/>
<ci>i_NaCa</ci>
<cn cellml:units="dimensionless">3</cn>
</apply>
<apply>
<times/>
<ci>i_NaK</ci>
<cn cellml:units="dimensionless">3</cn>
</apply>
</apply>
</apply>
<ci>A_cap</ci>
</apply>
<apply>
<times/>
<ci>V_myo</ci>
<ci>F</ci>
</apply>
</apply>
</apply>
<apply>
<eq/>
<apply>
<diff/>
<bvar>
<ci>time</ci>
</bvar>
<ci>Ki</ci>
</apply>
<apply>
<divide/>
<apply>
<times/>
<apply>
<minus/>
<apply>
<plus/>
<ci>i_CaK</ci>
<ci>i_Kr</ci>
<ci>i_Ks</ci>
<ci>i_K1</ci>
<ci>i_Kp</ci>
<ci>i_K_Na</ci>
<ci>i_K_ATP</ci>
<ci>i_to</ci>
<ci>i_ns_K</ci>
<apply>
<times/>
<apply>
<minus/>
<ci>i_NaK</ci>
</apply>
<cn cellml:units="dimensionless">2</cn>
</apply>
</apply>
</apply>
<ci>A_cap</ci>
</apply>
<apply>
<times/>
<ci>V_myo</ci>
<ci>F</ci>
</apply>
</apply>
</apply>
</math>
</component>
<group>
<relationship_ref relationship="containment"/>
<component_ref component="membrane">
<component_ref component="fast_sodium_current">
<component_ref component="Na_channel_states"/>
</component_ref>
<component_ref component="L_type_Ca_channel">
<component_ref component="L_type_Ca_channel_d_gate"/>
<component_ref component="L_type_Ca_channel_f_gate"/>
<component_ref component="L_type_Ca_channel_f_Ca_gate"/>
</component_ref>
<component_ref component="T_type_Ca_channel">
<component_ref component="T_type_Ca_channel_b_gate"/>
<component_ref component="T_type_Ca_channel_g_gate"/>
</component_ref>
<component_ref component="rapid_delayed_rectifier_potassium_current">
<component_ref component="Kr_channel_states"/>
</component_ref>
<component_ref component="slow_delayed_rectifier_potassium_current">
<component_ref component="slow_delayed_rectifier_potassium_current_xs1_gate"/>
<component_ref component="slow_delayed_rectifier_potassium_current_xs2_gate"/>
</component_ref>
<component_ref component="time_independent_potassium_current">
<component_ref component="time_independent_potassium_current_K1_gate"/>
</component_ref>
<component_ref component="transient_outward_current">
<component_ref component="transient_outward_current_zdv_gate"/>
<component_ref component="transient_outward_current_ydv_gate"/>
</component_ref>
<component_ref component="Na_Ca_exchanger"/>
<component_ref component="plateau_potassium_current"/>
<component_ref component="sodium_activated_potassium_current"/>
<component_ref component="ATP_sensitive_potassium_current"/>
<component_ref component="sarcolemmal_calcium_pump"/>
<component_ref component="sodium_background_current"/>
<component_ref component="calcium_background_current"/>
<component_ref component="sodium_potassium_pump"/>
<component_ref component="non_specific_calcium_activated_current"/>
<component_ref component="ionic_concentrations"/>
<component_ref component="calcium_dynamics"/>
</component_ref>
</group>
<group>
<relationship_ref relationship="encapsulation"/>
<component_ref component="fast_sodium_current">
<component_ref component="Na_channel_states"/>
</component_ref>
<component_ref component="L_type_Ca_channel">
<component_ref component="L_type_Ca_channel_d_gate"/>
<component_ref component="L_type_Ca_channel_f_gate"/>
<component_ref component="L_type_Ca_channel_f_Ca_gate"/>
</component_ref>
<component_ref component="T_type_Ca_channel">
<component_ref component="T_type_Ca_channel_b_gate"/>
<component_ref component="T_type_Ca_channel_g_gate"/>
</component_ref>
<component_ref component="rapid_delayed_rectifier_potassium_current">
<component_ref component="Kr_channel_states"/>
</component_ref>
<component_ref component="slow_delayed_rectifier_potassium_current">
<component_ref component="slow_delayed_rectifier_potassium_current_xs1_gate"/>
<component_ref component="slow_delayed_rectifier_potassium_current_xs2_gate"/>
</component_ref>
<component_ref component="time_independent_potassium_current">
<component_ref component="time_independent_potassium_current_K1_gate"/>
</component_ref>
<component_ref component="transient_outward_current">
<component_ref component="transient_outward_current_zdv_gate"/>
<component_ref component="transient_outward_current_ydv_gate"/>
</component_ref>
</group>
<connection>
<map_components component_1="membrane" component_2="environment"/>
<map_variables variable_1="time" variable_2="time"/>
</connection>
<connection>
<map_components component_1="fast_sodium_current" component_2="environment"/>
<map_variables variable_1="time" variable_2="time"/>
</connection>
<connection>
<map_components component_1="L_type_Ca_channel" component_2="environment"/>
<map_variables variable_1="time" variable_2="time"/>
</connection>
<connection>
<map_components component_1="T_type_Ca_channel" component_2="environment"/>
<map_variables variable_1="time" variable_2="time"/>
</connection>
<connection>
<map_components component_1="rapid_delayed_rectifier_potassium_current" component_2="environment"/>
<map_variables variable_1="time" variable_2="time"/>
</connection>
<connection>
<map_components component_1="slow_delayed_rectifier_potassium_current" component_2="environment"/>
<map_variables variable_1="time" variable_2="time"/>
</connection>
<connection>
<map_components component_1="time_independent_potassium_current" component_2="environment"/>
<map_variables variable_1="time" variable_2="time"/>
</connection>
<connection>
<map_components component_1="transient_outward_current" component_2="environment"/>
<map_variables variable_1="time" variable_2="time"/>
</connection>
<connection>
<map_components component_1="Na_Ca_exchanger" component_2="environment"/>
<map_variables variable_1="time" variable_2="time"/>
</connection>
<connection>
<map_components component_1="plateau_potassium_current" component_2="environment"/>
<map_variables variable_1="time" variable_2="time"/>
</connection>
<connection>
<map_components component_1="sarcolemmal_calcium_pump" component_2="environment"/>
<map_variables variable_1="time" variable_2="time"/>
</connection>
<connection>
<map_components component_1="sodium_background_current" component_2="environment"/>
<map_variables variable_1="time" variable_2="time"/>
</connection>
<connection>
<map_components component_1="calcium_background_current" component_2="environment"/>
<map_variables variable_1="time" variable_2="time"/>
</connection>
<connection>
<map_components component_1="sodium_potassium_pump" component_2="environment"/>
<map_variables variable_1="time" variable_2="time"/>
</connection>
<connection>
<map_components component_1="sodium_activated_potassium_current" component_2="environment"/>
<map_variables variable_1="time" variable_2="time"/>
</connection>
<connection>
<map_components component_1="ATP_sensitive_potassium_current" component_2="environment"/>
<map_variables variable_1="time" variable_2="time"/>
</connection>
<connection>
<map_components component_1="non_specific_calcium_activated_current" component_2="environment"/>
<map_variables variable_1="time" variable_2="time"/>
</connection>
<connection>
<map_components component_1="ionic_concentrations" component_2="environment"/>
<map_variables variable_1="time" variable_2="time"/>
</connection>
<connection>
<map_components component_1="calcium_dynamics" component_2="environment"/>
<map_variables variable_1="time" variable_2="time"/>
</connection>
<connection>
<map_components component_1="membrane" component_2="fast_sodium_current"/>
<map_variables variable_1="V" variable_2="V"/>
<map_variables variable_1="i_Na" variable_2="i_Na"/>
<map_variables variable_1="R" variable_2="R"/>
<map_variables variable_1="T" variable_2="T"/>
<map_variables variable_1="F" variable_2="F"/>
</connection>
<connection>
<map_components component_1="membrane" component_2="L_type_Ca_channel"/>
<map_variables variable_1="V" variable_2="V"/>
<map_variables variable_1="i_Ca_L" variable_2="i_Ca_L"/>
<map_variables variable_1="R" variable_2="R"/>
<map_variables variable_1="T" variable_2="T"/>
<map_variables variable_1="F" variable_2="F"/>
</connection>
<connection>
<map_components component_1="membrane" component_2="T_type_Ca_channel"/>
<map_variables variable_1="V" variable_2="V"/>
<map_variables variable_1="i_Ca_T" variable_2="i_Ca_T"/>
</connection>
<connection>
<map_components component_1="membrane" component_2="rapid_delayed_rectifier_potassium_current"/>
<map_variables variable_1="V" variable_2="V"/>
<map_variables variable_1="i_Kr" variable_2="i_Kr"/>
<map_variables variable_1="R" variable_2="R"/>
<map_variables variable_1="T" variable_2="T"/>
<map_variables variable_1="F" variable_2="F"/>
</connection>
<connection>
<map_components component_1="membrane" component_2="slow_delayed_rectifier_potassium_current"/>
<map_variables variable_1="V" variable_2="V"/>
<map_variables variable_1="i_Ks" variable_2="i_Ks"/>
<map_variables variable_1="R" variable_2="R"/>
<map_variables variable_1="T" variable_2="T"/>
<map_variables variable_1="F" variable_2="F"/>
</connection>
<connection>
<map_components component_1="membrane" component_2="sodium_activated_potassium_current"/>
<map_variables variable_1="V" variable_2="V"/>
<map_variables variable_1="i_K_Na" variable_2="i_K_Na"/>
</connection>
<connection>
<map_components component_1="membrane" component_2="ATP_sensitive_potassium_current"/>
<map_variables variable_1="V" variable_2="V"/>
<map_variables variable_1="i_K_ATP" variable_2="i_K_ATP"/>
</connection>
<connection>
<map_components component_1="membrane" component_2="transient_outward_current"/>
<map_variables variable_1="V" variable_2="V"/>
<map_variables variable_1="i_to" variable_2="i_to"/>
</connection>
<connection>
<map_components component_1="membrane" component_2="Na_Ca_exchanger"/>
<map_variables variable_1="V" variable_2="V"/>
<map_variables variable_1="i_NaCa" variable_2="i_NaCa"/>
<map_variables variable_1="R" variable_2="R"/>
<map_variables variable_1="T" variable_2="T"/>
<map_variables variable_1="F" variable_2="F"/>
</connection>
<connection>
<map_components component_1="membrane" component_2="time_independent_potassium_current"/>
<map_variables variable_1="V" variable_2="V"/>
<map_variables variable_1="i_K1" variable_2="i_K1"/>
<map_variables variable_1="R" variable_2="R"/>
<map_variables variable_1="T" variable_2="T"/>
<map_variables variable_1="F" variable_2="F"/>
</connection>
<connection>
<map_components component_1="membrane" component_2="plateau_potassium_current"/>
<map_variables variable_1="V" variable_2="V"/>
<map_variables variable_1="i_Kp" variable_2="i_Kp"/>
</connection>
<connection>
<map_components component_1="membrane" component_2="sarcolemmal_calcium_pump"/>
<map_variables variable_1="i_p_Ca" variable_2="i_p_Ca"/>
</connection>
<connection>
<map_components component_1="membrane" component_2="sodium_background_current"/>
<map_variables variable_1="V" variable_2="V"/>
<map_variables variable_1="i_Na_b" variable_2="i_Na_b"/>
</connection>
<connection>
<map_components component_1="membrane" component_2="calcium_background_current"/>
<map_variables variable_1="V" variable_2="V"/>
<map_variables variable_1="i_Ca_b" variable_2="i_Ca_b"/>
<map_variables variable_1="R" variable_2="R"/>
<map_variables variable_1="T" variable_2="T"/>
<map_variables variable_1="F" variable_2="F"/>
</connection>
<connection>
<map_components component_1="membrane" component_2="sodium_potassium_pump"/>
<map_variables variable_1="V" variable_2="V"/>
<map_variables variable_1="i_NaK" variable_2="i_NaK"/>
<map_variables variable_1="R" variable_2="R"/>
<map_variables variable_1="T" variable_2="T"/>
<map_variables variable_1="F" variable_2="F"/>
</connection>
<connection>
<map_components component_1="membrane" component_2="non_specific_calcium_activated_current"/>
<map_variables variable_1="V" variable_2="V"/>
<map_variables variable_1="R" variable_2="R"/>
<map_variables variable_1="T" variable_2="T"/>
<map_variables variable_1="F" variable_2="F"/>
<map_variables variable_1="i_ns_Ca" variable_2="i_ns_Ca"/>
</connection>
<connection>
<map_components component_1="membrane" component_2="ionic_concentrations"/>
<map_variables variable_1="F" variable_2="F"/>
</connection>
<connection>
<map_components component_1="membrane" component_2="calcium_dynamics"/>
<map_variables variable_1="F" variable_2="F"/>
<map_variables variable_1="dVdt" variable_2="dVdt"/>
</connection>
<connection>
<map_components component_1="fast_sodium_current" component_2="ionic_concentrations"/>
<map_variables variable_1="i_Na" variable_2="i_Na"/>
<map_variables variable_1="Nao" variable_2="Nao"/>
<map_variables variable_1="Nai" variable_2="Nai"/>
</connection>
<connection>
<map_components component_1="fast_sodium_current" component_2="sodium_background_current"/>
<map_variables variable_1="E_Na" variable_2="E_Na"/>
</connection>
<connection>
<map_components component_1="L_type_Ca_channel" component_2="ionic_concentrations"/>
<map_variables variable_1="Nao" variable_2="Nao"/>
<map_variables variable_1="Nai" variable_2="Nai"/>
<map_variables variable_1="Ko" variable_2="Ko"/>
<map_variables variable_1="Ki" variable_2="Ki"/>
<map_variables variable_1="i_CaNa" variable_2="i_CaNa"/>
<map_variables variable_1="i_CaK" variable_2="i_CaK"/>
</connection>
<connection>
<map_components component_1="L_type_Ca_channel" component_2="calcium_dynamics"/>
<map_variables variable_1="Cai" variable_2="Cai"/>
<map_variables variable_1="Cao" variable_2="Cao"/>
<map_variables variable_1="i_CaCa" variable_2="i_CaCa"/>
</connection>
<connection>
<map_components component_1="T_type_Ca_channel" component_2="calcium_dynamics"/>
<map_variables variable_1="i_Ca_T" variable_2="i_Ca_T"/>
</connection>
<connection>
<map_components component_1="slow_delayed_rectifier_potassium_current" component_2="ionic_concentrations"/>
<map_variables variable_1="Ki" variable_2="Ki"/>
<map_variables variable_1="Ko" variable_2="Ko"/>
<map_variables variable_1="Nao" variable_2="Nao"/>
<map_variables variable_1="Nai" variable_2="Nai"/>
<map_variables variable_1="i_Ks" variable_2="i_Ks"/>
</connection>
<connection>
<map_components component_1="slow_delayed_rectifier_potassium_current" component_2="calcium_dynamics"/>
<map_variables variable_1="Cai" variable_2="Cai"/>
</connection>
<connection>
<map_components component_1="rapid_delayed_rectifier_potassium_current" component_2="ionic_concentrations"/>
<map_variables variable_1="Ki" variable_2="Ki"/>
<map_variables variable_1="Ko" variable_2="Ko"/>
<map_variables variable_1="i_Kr" variable_2="i_Kr"/>
</connection>
<connection>
<map_components component_1="transient_outward_current" component_2="ionic_concentrations"/>
<map_variables variable_1="i_to" variable_2="i_to"/>
</connection>
<connection>
<map_components component_1="Na_Ca_exchanger" component_2="ionic_concentrations"/>
<map_variables variable_1="Nai" variable_2="Nai"/>
<map_variables variable_1="Nao" variable_2="Nao"/>
<map_variables variable_1="i_NaCa" variable_2="i_NaCa"/>
</connection>
<connection>
<map_components component_1="Na_Ca_exchanger" component_2="calcium_dynamics"/>
<map_variables variable_1="Cai" variable_2="Cai"/>
<map_variables variable_1="Cao" variable_2="Cao"/>
<map_variables variable_1="i_NaCa" variable_2="i_NaCa"/>
</connection>
<connection>
<map_components component_1="time_independent_potassium_current" component_2="ionic_concentrations"/>
<map_variables variable_1="Ki" variable_2="Ki"/>
<map_variables variable_1="Ko" variable_2="Ko"/>
<map_variables variable_1="i_K1" variable_2="i_K1"/>
</connection>
<connection>
<map_components component_1="sodium_activated_potassium_current" component_2="ionic_concentrations"/>
<map_variables variable_1="Nai" variable_2="Nai"/>
<map_variables variable_1="i_K_Na" variable_2="i_K_Na"/>
</connection>
<connection>
<map_components component_1="ATP_sensitive_potassium_current" component_2="ionic_concentrations"/>
<map_variables variable_1="Ko" variable_2="Ko"/>
<map_variables variable_1="i_K_ATP" variable_2="i_K_ATP"/>
</connection>
<connection>
<map_components component_1="plateau_potassium_current" component_2="time_independent_potassium_current"/>
<map_variables variable_1="E_K" variable_2="E_K"/>
</connection>
<connection>
<map_components component_1="sodium_activated_potassium_current" component_2="time_independent_potassium_current"/>
<map_variables variable_1="E_K" variable_2="E_K"/>
</connection>
<connection>
<map_components component_1="ATP_sensitive_potassium_current" component_2="time_independent_potassium_current"/>
<map_variables variable_1="E_K" variable_2="E_K"/>
</connection>
<connection>
<map_components component_1="transient_outward_current" component_2="time_independent_potassium_current"/>
<map_variables variable_1="E_K" variable_2="E_K"/>
</connection>
<connection>
<map_components component_1="plateau_potassium_current" component_2="ionic_concentrations"/>
<map_variables variable_1="i_Kp" variable_2="i_Kp"/>
</connection>
<connection>
<map_components component_1="sarcolemmal_calcium_pump" component_2="calcium_dynamics"/>
<map_variables variable_1="i_p_Ca" variable_2="i_p_Ca"/>
<map_variables variable_1="Cai" variable_2="Cai"/>
</connection>
<connection>
<map_components component_1="T_type_Ca_channel" component_2="calcium_background_current"/>
<map_variables variable_1="E_Ca" variable_2="E_Ca"/>
</connection>
<connection>
<map_components component_1="sodium_background_current" component_2="ionic_concentrations"/>
<map_variables variable_1="i_Na_b" variable_2="i_Na_b"/>
</connection>
<connection>
<map_components component_1="calcium_background_current" component_2="calcium_dynamics"/>
<map_variables variable_1="Cai" variable_2="Cai"/>
<map_variables variable_1="Cao" variable_2="Cao"/>
<map_variables variable_1="i_Ca_b" variable_2="i_Ca_b"/>
</connection>
<connection>
<map_components component_1="sodium_potassium_pump" component_2="ionic_concentrations"/>
<map_variables variable_1="Nai" variable_2="Nai"/>
<map_variables variable_1="Nao" variable_2="Nao"/>
<map_variables variable_1="Ko" variable_2="Ko"/>
<map_variables variable_1="i_NaK" variable_2="i_NaK"/>
</connection>
<connection>
<map_components component_1="non_specific_calcium_activated_current" component_2="ionic_concentrations"/>
<map_variables variable_1="Nao" variable_2="Nao"/>
<map_variables variable_1="Nai" variable_2="Nai"/>
<map_variables variable_1="Ko" variable_2="Ko"/>
<map_variables variable_1="Ki" variable_2="Ki"/>
<map_variables variable_1="i_ns_Na" variable_2="i_ns_Na"/>
<map_variables variable_1="i_ns_K" variable_2="i_ns_K"/>
</connection>
<connection>
<map_components component_1="non_specific_calcium_activated_current" component_2="calcium_dynamics"/>
<map_variables variable_1="Cai" variable_2="Cai"/>
<map_variables variable_1="Cao" variable_2="Cao"/>
</connection>
<connection>
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<rdf:Description xmlns:rdf="http://www.w3.org/1999/02/22-rdf-syntax-ns#" rdf:about="rdf:#23a1cbd8-03b0-4701-a21a-7431792c7bf0">
<vCard:Given xmlns:vCard="http://www.w3.org/2001/vcard-rdf/3.0#">James</vCard:Given>
<vCard:Family xmlns:vCard="http://www.w3.org/2001/vcard-rdf/3.0#">Lawson</vCard:Family>
<vCard:Other xmlns:vCard="http://www.w3.org/2001/vcard-rdf/3.0#">Richard</vCard:Other>
</rdf:Description>
<rdf:Description xmlns:rdf="http://www.w3.org/1999/02/22-rdf-syntax-ns#" rdf:about="rdf:#b117ebec-647a-46a3-9edd-e49c3395f906">
<dcterms:W3CDTF xmlns:dcterms="http://purl.org/dc/terms/">2003-08-20T00:00:00+00:00</dcterms:W3CDTF>
</rdf:Description>
<rdf:Description xmlns:rdf="http://www.w3.org/1999/02/22-rdf-syntax-ns#" rdf:about="rdf:#0a232fa0-1166-4841-9e92-e410fd7aa7e3">
<vCard:N xmlns:vCard="http://www.w3.org/2001/vcard-rdf/3.0#" rdf:resource="rdf:#23a1cbd8-03b0-4701-a21a-7431792c7bf0" xmlns:rdf="http://www.w3.org/1999/02/22-rdf-syntax-ns#"/>
</rdf:Description>
</rdf:RDF>
</model>
