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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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<title>Model Status</title>
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This CellML model represents the wildtype endocardial cell. For more details on the curation status of this model please see this <ulink url="Clancy_Rudy_Mutations.pdf">separate notes document</ulink>.
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<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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<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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<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>
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<apply>
<minus/>
<ci>V</ci>
</apply>
<cn cellml:units="millivolt">20.3</cn>
</apply>
</apply>
</apply>
</apply>
<apply>
<eq/>
<ci>beta_12</ci>
<apply>
<times/>
<cn cellml:units="per_second">200</cn>
<apply>
<exp/>
<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" units="microA_per_microF" public_interface="out"/>
<variable name="i_CaCa" units="microA_per_microF" public_interface="out"/>
<variable name="i_CaK" units="microA_per_microF" public_interface="out"/>
<variable name="i_CaNa" units="microA_per_microF" public_interface="out"/>
<variable name="gamma_Nai" units="dimensionless" initial_value="0.75" public_interface="out"/>
<variable name="gamma_Nao" units="dimensionless" initial_value="0.75" public_interface="out"/>
<variable name="gamma_Ki" units="dimensionless" initial_value="0.75" public_interface="out"/>
<variable name="gamma_Ko" units="dimensionless" initial_value="0.75" public_interface="out"/>
<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 name="P_Ca" units="cm_per_second" initial_value="0.00054"/>
<variable name="P_Na" units="cm_per_second" initial_value="6.75e-7"/>
<variable name="P_K" units="cm_per_second" initial_value="1.93e-7"/>
<variable name="gamma_Cai" units="dimensionless" initial_value="1"/>
<variable name="gamma_Cao" units="dimensionless" initial_value="0.341"/>
<variable name="time" units="second" public_interface="in" private_interface="out"/>
<variable name="V" units="millivolt" public_interface="in" private_interface="out"/>
<variable name="Cai" units="millimolar" public_interface="in" private_interface="out"/>
<variable name="R" units="joule_per_kilomole_kelvin" public_interface="in"/>
<variable name="T" units="kelvin" public_interface="in"/>
<variable name="F" units="coulomb_per_mole" public_interface="in"/>
<variable name="Cao" units="millimolar" public_interface="in"/>
<variable name="Nao" units="millimolar" public_interface="in"/>
<variable name="Ko" units="millimolar" public_interface="in"/>
<variable name="Nai" units="millimolar" public_interface="in"/>
<variable name="Ki" units="millimolar" public_interface="in"/>
<variable name="d" units="dimensionless" private_interface="in"/>
<variable name="f" units="dimensionless" private_interface="in"/>
<variable name="f_Ca" units="dimensionless" private_interface="in"/>
<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 name="d" units="dimensionless" initial_value="3.085e-6" public_interface="out"/>
<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" units="millivolt" public_interface="in"/>
<variable name="time" units="second" public_interface="in"/>
<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 name="f" units="dimensionless" initial_value="0.9998" public_interface="out"/>
<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" units="millivolt" public_interface="in"/>
<variable name="time" units="second" public_interface="in"/>
<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" units="dimensionless" public_interface="out"/>
<variable name="Km_Ca" units="millimolar" initial_value="0.0006"/>
<variable name="V" units="millivolt" public_interface="in"/>
<variable name="time" units="second" public_interface="in"/>
<variable name="Cai" units="millimolar" public_interface="in"/>
<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" units="microA_per_microF" public_interface="out"/>
<variable name="g_CaT" units="milliS_per_microF" initial_value="0.05"/>
<variable name="E_Ca" units="millivolt" public_interface="in"/>
<variable name="time" units="second" public_interface="in" private_interface="out"/>
<variable name="V" units="millivolt" public_interface="in" private_interface="out"/>
<variable name="b" units="dimensionless" private_interface="in"/>
<variable name="g" units="dimensionless" private_interface="in"/>
<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 name="b" units="dimensionless" initial_value="0.000947" public_interface="out"/>
<variable name="V" units="millivolt" public_interface="in"/>
<variable name="time" units="second" public_interface="in"/>
<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 name="g" units="dimensionless" initial_value="0.99457" public_interface="out"/>
<variable name="V" units="millivolt" public_interface="in"/>
<variable name="time" units="second" public_interface="in"/>
<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" units="microA_per_microF" public_interface="out"/>
<variable name="g_Kr" units="milliS_per_microF"/>
<variable name="E_Kr" units="millivolt"/>
<variable name="time" units="second" public_interface="in" private_interface="out"/>
<variable name="V" units="millivolt" public_interface="in" private_interface="out"/>
<variable name="Ko" units="millimolar" public_interface="in" private_interface="out"/>
<variable name="Ki" units="millimolar" public_interface="in"/>
<variable name="R" units="joule_per_kilomole_kelvin" public_interface="in"/>
<variable name="T" units="kelvin" public_interface="in"/>
<variable name="F" units="coulomb_per_mole" public_interface="in"/>
<variable name="P_O" units="dimensionless" private_interface="in"/>
<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 name="P_O" units="dimensionless" initial_value="1.032e-10" public_interface="out"/>
<variable name="P_C1" units="dimensionless" initial_value="3.2864e-8"/>
<variable name="P_C2" units="dimensionless" initial_value="1.63e-8"/>
<variable name="P_C3" units="dimensionless" initial_value="4.951e-6"/>
<variable name="P_I" units="dimensionless" initial_value="3.135e-11"/>
<variable name="alpha" units="per_second"/>
<variable name="beta" units="per_second"/>
<variable name="alpha_in" units="per_second" initial_value="2172"/>
<variable name="beta_in" units="per_second" initial_value="1077"/>
<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" units="second" public_interface="in"/>
<variable name="V" units="millivolt" public_interface="in"/>
<variable name="Ko" units="millimolar" public_interface="in"/>
<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="micromolar">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="micromolar">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" units="microA_per_microF" public_interface="out"/>
<variable name="g_Ks" units="milliS_per_microF"/>
<variable name="E_Ks" units="millivolt"/>
<variable name="PNaK" units="dimensionless" initial_value="0.01833"/>
<variable name="time" units="second" public_interface="in" private_interface="out"/>
<variable name="V" units="millivolt" public_interface="in" private_interface="out"/>
<variable name="R" units="joule_per_kilomole_kelvin" public_interface="in"/>
<variable name="T" units="kelvin" public_interface="in"/>
<variable name="F" units="coulomb_per_mole" public_interface="in"/>
<variable name="Ko" units="millimolar" public_interface="in"/>
<variable name="Ki" units="millimolar" public_interface="in"/>
<variable name="Nao" units="millimolar" public_interface="in"/>
<variable name="Nai" units="millimolar" public_interface="in"/>
<variable name="Cai" units="millimolar" public_interface="in"/>
<variable name="xs1" units="dimensionless" private_interface="in"/>
<variable name="xs2" units="dimensionless" private_interface="in"/>
<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">0.968</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 name="xs1" units="dimensionless" initial_value="0.00437" public_interface="out"/>
<variable name="xs1_infinity" units="dimensionless"/>
<variable name="tau_xs1" units="second"/>
<variable name="V" units="millivolt" public_interface="in"/>
<variable name="time" units="second" public_interface="in"/>
<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 name="xs2" units="dimensionless" initial_value="0.00437" public_interface="out"/>
<variable name="xs2_infinity" units="dimensionless"/>
<variable name="tau_xs2" units="second"/>
<variable name="V" units="millivolt" public_interface="in"/>
<variable name="time" units="second" public_interface="in"/>
<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" units="microA_per_microF" public_interface="out"/>
<variable name="E_K" units="millivolt" public_interface="out" private_interface="out"/>
<variable name="g_K1" units="milliS_per_cm2"/>
<variable name="time" units="second" public_interface="in" private_interface="out"/>
<variable name="V" units="millivolt" public_interface="in" private_interface="out"/>
<variable name="Ko" units="millimolar" public_interface="in"/>
<variable name="Ki" units="millimolar" public_interface="in"/>
<variable name="R" units="joule_per_kilomole_kelvin" public_interface="in"/>
<variable name="T" units="kelvin" public_interface="in"/>
<variable name="F" units="coulomb_per_mole" public_interface="in"/>
<variable name="K1_infinity" units="dimensionless" private_interface="in"/>
<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" units="dimensionless" public_interface="out"/>
<variable name="alpha_K1" units="per_second"/>
<variable name="beta_K1" units="per_second"/>
<variable name="V" units="millivolt" public_interface="in"/>
<variable name="time" units="second" public_interface="in"/>
<variable name="E_K" units="millivolt" public_interface="in"/>
<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" units="microA_per_microF" public_interface="out"/>
<variable name="g_Kp" units="milliS_per_microF" initial_value="0.00552"/>
<variable name="Kp" units="dimensionless"/>
<variable name="time" units="second" public_interface="in"/>
<variable name="V" units="millivolt" public_interface="in"/>
<variable name="E_K" units="millivolt" public_interface="in"/>
<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" units="microA_per_microF" public_interface="out"/>
<variable name="g_K_Na" units="milliS_per_microF"/>
<variable name="nKNa" units="dimensionless" initial_value="2.8"/>
<variable name="pona" units="dimensionless"/>
<variable name="pov" units="dimensionless"/>
<variable name="kdKNa" units="millimolar" initial_value="66"/>
<variable name="time" units="second" public_interface="in"/>
<variable name="V" units="millivolt" public_interface="in"/>
<variable name="Nai" units="millimolar" public_interface="in"/>
<variable name="E_K" units="millivolt" public_interface="in"/>
<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" units="microA_per_microF" public_interface="out"/>
<variable name="g_K_ATP" units="milliS_per_microF"/>
<variable name="i_K_ATP_on" units="dimensionless" initial_value="1"/>
<variable name="nATP" units="dimensionless" initial_value="0.24"/>
<variable name="nicholsarea" units="dimensionless" initial_value="5e-5"/>
<variable name="ATPi" units="millimolar" initial_value="3"/>
<variable name="hATP" units="dimensionless" initial_value="2"/>
<variable name="kATP" units="millimolar" initial_value="0.00025"/>
<variable name="pATP" units="dimensionless"/>
<variable name="GKbaraATP" units="milliS_per_microF"/>
<variable name="time" units="second" public_interface="in"/>
<variable name="V" units="millivolt" public_interface="in"/>
<variable name="Ko" units="millimolar" public_interface="in"/>
<variable name="E_K" units="millivolt" public_interface="in"/>
<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" units="microA_per_microF" public_interface="out"/>
<variable name="g_to" units="milliS_per_microF"/>
<variable name="E_K" units="millivolt" public_interface="in"/>
<variable name="V" units="millivolt" public_interface="in" private_interface="out"/>
<variable name="time" units="second" public_interface="in" private_interface="out"/>
<variable name="rvdv" units="dimensionless"/>
<variable name="zdv" units="dimensionless" private_interface="in"/>
<variable name="ydv" units="dimensionless" private_interface="in"/>
<math xmlns="http://www.w3.org/1998/Math/MathML">
<apply>
<eq/>
<ci>g_to</ci>
<cn cellml:units="milliS_per_microF">0.05</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 name="zdv" units="dimensionless" initial_value="0.0114" public_interface="out"/>
<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" units="millivolt" public_interface="in"/>
<variable name="time" units="second" public_interface="in"/>
<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 name="ydv" units="dimensionless" initial_value="0.99998" public_interface="out"/>
<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" units="millivolt" public_interface="in"/>
<variable name="time" units="second" public_interface="in"/>
<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" units="microA_per_microF" public_interface="out"/>
<variable name="K_mpCa" units="millimolar" initial_value="0.0005"/>
<variable name="I_pCa" units="microA_per_microF" initial_value="1.15"/>
<variable name="time" units="second" public_interface="in"/>
<variable name="Cai" units="millimolar" public_interface="in"/>
<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" units="microA_per_microF" public_interface="out"/>
<variable name="g_Nab" units="milliS_per_microF" initial_value="0.004"/>
<variable name="time" units="second" public_interface="in"/>
<variable name="V" units="millivolt" public_interface="in"/>
<variable name="E_Na" units="millivolt" public_interface="in"/>
<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" units="microA_per_microF" public_interface="out"/>
<variable name="g_Cab" units="milliS_per_microF" initial_value="0.003016"/>
<variable name="E_Ca" units="millivolt" public_interface="out"/>
<variable name="time" units="second" public_interface="in"/>
<variable name="V" units="millivolt" public_interface="in"/>
<variable name="R" units="joule_per_kilomole_kelvin" public_interface="in"/>
<variable name="T" units="kelvin" public_interface="in"/>
<variable name="F" units="coulomb_per_mole" public_interface="in"/>
<variable name="Cai" units="millimolar" public_interface="in"/>
<variable name="Cao" units="millimolar" public_interface="in"/>
<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" units="microA_per_microF" public_interface="out"/>
<variable name="I_NaK" units="microA_per_microF" initial_value="2.25"/>
<variable name="f_NaK" units="dimensionless"/>
<variable name="K_mNai" units="millimolar" initial_value="10"/>
<variable name="K_mKo" units="millimolar" initial_value="1.5"/>
<variable name="sigma" units="dimensionless"/>
<variable name="time" units="second" public_interface="in"/>
<variable name="V" units="millivolt" public_interface="in"/>
<variable name="R" units="joule_per_kilomole_kelvin" public_interface="in"/>
<variable name="T" units="kelvin" public_interface="in"/>
<variable name="F" units="coulomb_per_mole" public_interface="in"/>
<variable name="Nai" units="millimolar" public_interface="in"/>
<variable name="Nao" units="millimolar" public_interface="in"/>
<variable name="Ko" units="millimolar" public_interface="in"/>
<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" units="microA_per_microF" public_interface="out"/>
<variable name="i_ns_Na" units="microA_per_microF" public_interface="out"/>
<variable name="i_ns_K" units="microA_per_microF" public_interface="out"/>
<variable name="P_ns_Ca" units="cm_per_second"/>
<variable name="gamma_Nai" units="dimensionless" public_interface="in"/>
<variable name="gamma_Nao" units="dimensionless" public_interface="in"/>
<variable name="gamma_Ki" units="dimensionless" public_interface="in"/>
<variable name="gamma_Ko" units="dimensionless" public_interface="in"/>
<variable name="R" units="joule_per_kilomole_kelvin" public_interface="in"/>
<variable name="T" units="kelvin" public_interface="in"/>
<variable name="F" units="coulomb_per_mole" public_interface="in"/>
<variable name="Cao" units="millimolar" public_interface="in"/>
<variable name="Nao" units="millimolar" public_interface="in"/>
<variable name="Ko" units="millimolar" public_interface="in"/>
<variable name="Nai" units="millimolar" public_interface="in"/>
<variable name="Ki" units="millimolar" public_interface="in"/>
<variable name="I_ns_Na" units="microA_per_microF"/>
<variable name="I_ns_K" units="microA_per_microF"/>
<variable name="K_m_ns_Ca" units="millimolar" initial_value="0.0012"/>
<variable name="time" units="second" public_interface="in"/>
<variable name="Cai" units="millimolar" public_interface="in"/>
<variable name="V" units="millivolt" public_interface="in"/>
<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" units="microA_per_microF" public_interface="out"/>
<variable name="c1" units="microA_per_microF" initial_value="0.00025"/>
<variable name="c2" units="millimolar" initial_value="0.0001"/>
<variable name="gamma" units="dimensionless" initial_value="0.15"/>
<variable name="time" units="second" public_interface="in"/>
<variable name="V" units="millivolt" public_interface="in"/>
<variable name="R" units="joule_per_kilomole_kelvin" public_interface="in"/>
<variable name="T" units="kelvin" public_interface="in"/>
<variable name="F" units="coulomb_per_mole" public_interface="in"/>
<variable name="Nai" units="millimolar" public_interface="in"/>
<variable name="Nao" units="millimolar" public_interface="in"/>
<variable name="Cai" units="millimolar" public_interface="in"/>
<variable name="Cao" units="millimolar" public_interface="in"/>
<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" units="millimolar_per_second" public_interface="out"/>
<variable name="i_up" units="millimolar_per_second" public_interface="out"/>
<variable name="i_leak" units="millimolar_per_second" public_interface="out"/>
<variable name="i_tr" units="millimolar_per_second" public_interface="out"/>
<variable name="G_rel" units="per_second"/>
<variable name="G_rel_max" units="per_second" initial_value="60000"/>
<variable name="G_rel_overload" units="per_second" initial_value="4000"/>
<variable name="tau_tr" units="second" initial_value="0.18"/>
<variable name="K_mrel" units="millimolar" initial_value="0.0008"/>
<variable name="delta_Ca_ith" units="millimolar" initial_value="0.00018"/>
<variable name="CSQN_max" units="millimolar" initial_value="10"/>
<variable name="K_mCSQN" units="millimolar" initial_value="0.8"/>
<variable name="K_mup" units="millimolar" initial_value="0.00092"/>
<variable name="K_leak" units="per_second"/>
<variable name="I_up" units="millimolar_per_second" initial_value="8.75"/>
<variable name="Ca_NSR_max" units="millimolar" initial_value="15"/>
<variable name="time" units="second" public_interface="in"/>
<variable name="F" units="coulomb_per_mole" public_interface="in"/>
<variable name="Cai" units="millimolar" initial_value="0.000123" public_interface="out"/>
<variable name="Cao" units="millimolar" initial_value="1.8" public_interface="out"/>
<variable name="Ca_JSR" units="millimolar" initial_value="1.763" public_interface="out"/>
<variable name="Ca_NSR" units="millimolar" initial_value="1.764" public_interface="out"/>
<variable name="V_myo" units="micro_litre" public_interface="in"/>
<variable name="A_cap" units="mm2" public_interface="in"/>
<variable name="V_JSR" units="micro_litre"/>
<variable name="V_NSR" units="micro_litre"/>
<variable name="i_NaCa" units="microA_per_microF" public_interface="in"/>
<variable name="i_CaCa" units="microA_per_microF" public_interface="in"/>
<variable name="i_p_Ca" units="microA_per_microF" public_interface="in"/>
<variable name="i_Ca_b" units="microA_per_microF" public_interface="in"/>
<variable name="i_Ca_T" units="microA_per_microF" public_interface="in"/>
<variable name="K_mTn" units="millimolar" initial_value="0.0005"/>
<variable name="K_mCMDN" units="millimolar" initial_value="0.00238"/>
<variable name="Tn_max" units="millimolar" initial_value="0.07"/>
<variable name="CMDN_max" units="millimolar" initial_value="0.05"/>
<variable name="dVdt" units="dimensionless" public_interface="in"/>
<variable name="APtrack" units="dimensionless" initial_value="0"/>
<variable name="APtrack2" units="dimensionless" initial_value="0"/>
<variable name="APtrack3" units="dimensionless" initial_value="0"/>
<variable name="Cainfluxtrack" units="dimensionless" initial_value="0"/>
<variable name="OVRLDtrack" units="dimensionless" initial_value="0"/>
<variable name="OVRLDtrack2" units="dimensionless" initial_value="0"/>
<variable name="OVRLDtrack3" units="dimensionless" initial_value="0"/>
<variable name="CSQNthresh" units="millimolar" initial_value="0.7"/>
<variable name="Logicthresh" units="dimensionless" initial_value="0.98"/>
<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 name="Nai" units="millimolar" initial_value="12.306" public_interface="out"/>
<variable name="Nao" units="millimolar" initial_value="132" public_interface="out"/>
<variable name="Ki" units="millimolar" initial_value="140.22" public_interface="out"/>
<variable name="Ko" units="millimolar" initial_value="4.5" public_interface="out"/>
<variable name="A_cap" units="mm2" initial_value="1.434e-7" public_interface="out"/>
<variable name="preplength" units="mm" initial_value="0.001"/>
<variable name="radius" units="mm" initial_value="1.1e-4"/>
<variable name="volume" units="micro_litre"/>
<variable name="V_myo" units="micro_litre" public_interface="out"/>
<variable name="time" units="second" public_interface="in"/>
<variable name="F" units="coulomb_per_mole" public_interface="in"/>
<variable name="i_Na" units="microA_per_microF" public_interface="in"/>
<variable name="i_CaNa" units="microA_per_microF" public_interface="in"/>
<variable name="i_Na_b" units="microA_per_microF" public_interface="in"/>
<variable name="i_ns_Na" units="microA_per_microF" public_interface="in"/>
<variable name="i_NaCa" units="microA_per_microF" public_interface="in"/>
<variable name="i_NaK" units="microA_per_microF" public_interface="in"/>
<variable name="i_CaK" units="microA_per_microF" public_interface="in"/>
<variable name="i_Kr" units="microA_per_microF" public_interface="in"/>
<variable name="i_Ks" units="microA_per_microF" public_interface="in"/>
<variable name="i_K1" units="microA_per_microF" public_interface="in"/>
<variable name="i_Kp" units="microA_per_microF" public_interface="in"/>
<variable name="i_K_Na" units="microA_per_microF" public_interface="in"/>
<variable name="i_K_ATP" units="microA_per_microF" public_interface="in"/>
<variable name="i_ns_K" units="microA_per_microF" public_interface="in"/>
<variable name="i_to" units="microA_per_microF" public_interface="in"/>
<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"/>
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<map_variables variable_1="Cao" variable_2="Cao"/>
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<connection>
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<map_variables variable_1="gamma_Ko" variable_2="gamma_Ko"/>
<map_variables variable_1="gamma_Ki" variable_2="gamma_Ki"/>
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<connection>
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<map_variables variable_1="P_O_Na" variable_2="P_O_Na"/>
<map_variables variable_1="time" variable_2="time"/>
<map_variables variable_1="V" variable_2="V"/>
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<connection>
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<connection>
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<connection>
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<connection>
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<connection>
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<connection>
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<map_variables variable_1="time" variable_2="time"/>
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<connection>
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<connection>
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<connection>
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<map_variables variable_1="K1_infinity" variable_2="K1_infinity"/>
<map_variables variable_1="E_K" variable_2="E_K"/>
<map_variables variable_1="time" variable_2="time"/>
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<connection>
<map_components component_1="transient_outward_current" component_2="transient_outward_current_ydv_gate"/>
<map_variables variable_1="ydv" variable_2="ydv"/>
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<map_variables variable_1="V" variable_2="V"/>
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<connection>
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<map_variables variable_1="zdv" variable_2="zdv"/>
<map_variables variable_1="time" variable_2="time"/>
<map_variables variable_1="V" variable_2="V"/>
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<connection>
<map_components component_1="calcium_dynamics" component_2="ionic_concentrations"/>
<map_variables variable_1="V_myo" variable_2="V_myo"/>
<map_variables variable_1="A_cap" variable_2="A_cap"/>
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<dc:title>Na Channel Mutation That Causes Both Brugada Syndrome and Long-QT Syndrome Phenotypes: A Simulation Study of Mechanism (Wild Type Endocardial Cell)</dc:title>
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removed publication link in documentation</rdf:value>
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<rdf:value>This model is currently unable to be supported due to its dependence on the Luo Rudy 1994 model, which contains delay elements in its model of the CIRC, which can not yet be represented in CellML (as of CellML 1.1). Therefore this model is unconstrained and does not load or run in any simulator.</rdf:value>
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<vCard:Given>Colleen</vCard:Given>
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<vCard:Other>E</vCard:Other>
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<rdf:value>Added value of 1.5e-2 to variable I_NaK (note, not i_NaK) in component "sodium_potassium_pump". This value was obtained from the LR94 dynamic model</rdf:value>
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<dc:title>Circulation</dc:title>
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<dcterms:W3CDTF>2002-03-12</dcterms:W3CDTF>
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