- Author:
- pmr2.import <nobody@models.cellml.org>
- Date:
- 2008-02-11 04:22:46+13:00
- Desc:
- committing version01 of hinch_greenstein_tanskanen_xu_winslow_2004
- Permanent Source URI:
- https://models.physiomeproject.org/workspace/hinch_greenstein_tanskanen_xu_winslow_2004/rawfile/87ed469acd6fb04dfdfcc6d67e4b556d65222682/hinch_greenstein_tanskanen_xu_winslow_2004.cellml
<?xml version='1.0' encoding='utf-8'?>
<!--
This CellML file was generated on 20/12/2007 at 3:22:13 at PM using:
COR (0.9.31.769)
Copyright 2002-2007 Dr Alan Garny
http://COR.physiol.ox.ac.uk/ - COR@physiol.ox.ac.uk
CellML 1.0 was used to generate this cellular model
http://www.CellML.org/
--><model xmlns="http://www.cellml.org/cellml/1.0#" xmlns:cmeta="http://www.cellml.org/metadata/1.0#" xmlns:dc="http://purl.org/dc/elements/1.1/" xmlns:rdf="http://www.w3.org/1999/02/22-rdf-syntax-ns#" xmlns:bqs="http://www.cellml.org/bqs/1.0#" xmlns:cellml="http://www.cellml.org/cellml/1.0#" xmlns:dcterms="http://purl.org/dc/terms/" xmlns:vCard="http://www.w3.org/2001/vcard-rdf/3.0#" xmlns:ns7="http://www.cellml.org/metadata/simulation/1.0#" name="Hinch" cmeta:id="Hinch_2004">
<documentation xmlns="http://cellml.org/tmp-documentation">
<article>
<section id="sec_status">
<title>Model Status</title>
<para>
This model is known to run in PCEnv and COR to reproduce the output shown in the publication. A PCEnv session file is also associated with this model.
</para>
</section>
<sect1 id="sec_structure">
<title>Model Structure</title>
<para>
This CellML model was based on the December 2004 paper:
</para>
<para>
"A Quantitative Analysis of Cardiac Myocyte Relaxation: A Simulation Study" by Hinch, Greenstein, Tanskanen, Xu and Winslow.
</para>
<para>
The following is the abstract of this paper:
</para>
<para>
Calcium (Ca2+)-induced Ca2+ release (CICR) in cardiac myocytes exhibits high gain and is graded. These properties result from local control of Ca2+ release. Existing local control models of Ca2+ release in which interactions between L-Type Ca2+ channels (LCCs) and ryanodine-sensitive Ca2+ release channels (RyRs) are simulated stochastically are able to reconstruct these properties, but only at high computational cost. Here we present a general analytical approach for deriving simplified models of local control of CICR, consisting of low-dimensional systems of coupled ordinary differential equations, from these more complex local control models in which LCC-RyR interactions are simulated stochastically. The resulting model, referred to as the coupled LCC-RyR gating model, successfully reproduces a range of experimental data, including L-Type Ca2+ current in response to voltage-clamp stimuli, inactivation of LCC current with and without Ca2+ release from the sarcoplasmic reticulum, voltage-dependence of excitation-contraction coupling gain, graded release, and the force-frequency relationship. The model does so with low computational cost.
</para>
<para>
The complete original publication reference is cited below:
</para>
<para>
<ulink url="http://www.biophysj.org/cgi/content/abstract/87/6/3723">A Simplified Local Control Model of Calcium-Induced Calcium Release in Cardiac Ventricular Myocytes</ulink>, R. Hinch, J.R. Greenstein, A.J. Tanskanen, L. Xu, R.L. Winslow, 2004 <ulink url="http://www.biophysj.org/">
<emphasis>Biophysical Journal</emphasis>
</ulink>, Volume 87 pp.3723-3736, PubMed ID: 15465866
</para>
<informalfigure float="0" id="cell_diagram">
<mediaobject>
<imageobject>
<objectinfo>
<title>state diagram</title>
</objectinfo>
<imagedata fileref="hinch_2004.png"/>
</imageobject>
</mediaobject>
<caption>Schematic diagram of the currents and the ion exchanges described by the cardiac ventricular myocyte model.</caption>
</informalfigure>
<informalfigure float="0" id="markov_diagram">
<mediaobject>
<imageobject>
<objectinfo>
<title>state diagram</title>
</objectinfo>
<imagedata fileref="hinch_2004b.png"/>
</imageobject>
</mediaobject>
<caption>The nine-state Markov model of the calcium release unit (CaRU). In state yij, the LCC is in the state i and the RyR is in the state j.</caption>
</informalfigure>
</sect1>
</article>
</documentation>
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<units name="ms">
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<units name="mV">
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<units name="C_per_mole">
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<component name="environment">
<variable units="ms" public_interface="out" name="time" cmeta:id="environment_time"/>
</component>
<component name="cell_geometry">
<variable units="um3" public_interface="out" name="V_myo" initial_value="25.84e3"/>
<variable units="um3" public_interface="out" name="V_SR" initial_value="2.098e3"/>
<variable units="um2" public_interface="out" name="A_cap" initial_value="1.534e4"/>
</component>
<component name="membrane">
<variable units="mV" public_interface="out" name="V"/>
<variable units="mJ_per_mole_K" public_interface="out" name="R" initial_value="8314.5"/>
<variable units="kelvin" public_interface="out" name="T" initial_value="295"/>
<variable units="C_per_mole" public_interface="out" name="F" initial_value="96487"/>
<variable units="ms" public_interface="in" name="time"/>
<variable units="dimensionless" public_interface="out" name="FVRT"/>
<variable units="dimensionless" public_interface="out" name="FVRT_Ca"/>
<math xmlns="http://www.w3.org/1998/Math/MathML">
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</component>
<component name="CaRU">
<variable units="um3_per_ms" private_interface="out" name="g_D" initial_value="0.065"/>
<variable units="um3_per_ms" private_interface="out" name="J_R" initial_value="0.02"/>
<variable units="um3_per_ms" private_interface="out" name="J_L" initial_value="9.13e-4"/>
<variable units="um3" public_interface="in" private_interface="out" name="V_myo"/>
<variable units="dimensionless" private_interface="out" name="N" initial_value="50000"/>
<variable units="mV" public_interface="in" private_interface="out" name="V"/>
<variable units="mM" public_interface="in" private_interface="out" name="Ca_i"/>
<variable units="mM" public_interface="in" private_interface="out" name="Ca_o"/>
<variable units="mM" public_interface="in" private_interface="out" name="Ca_SR"/>
<variable units="ms" public_interface="in" private_interface="out" name="time"/>
<variable units="dimensionless" public_interface="in" private_interface="out" name="FVRT_Ca"/>
<variable units="mM_per_ms" public_interface="out" private_interface="in" name="I_RyR"/>
<variable units="mM_per_ms" public_interface="out" private_interface="in" name="I_LCC"/>
</component>
<component name="CaRU_Transitions">
<variable units="mV" public_interface="in" name="V"/>
<variable units="mM" public_interface="in" name="C_oc"/>
<variable units="mM" public_interface="in" name="C_co"/>
<variable units="mM" public_interface="in" name="Ca_i"/>
<variable units="mV" name="V_L" initial_value="-2"/>
<variable units="mV" name="del_VL" initial_value="7"/>
<variable units="dimensionless" name="phi_L" initial_value="2.35"/>
<variable units="ms" name="t_L" initial_value="1"/>
<variable units="ms" name="tau_L" initial_value="650"/>
<variable units="ms" name="t_R"/>
<variable units="ms" name="tau_R" initial_value="2.43"/>
<variable units="dimensionless" name="phi_R" initial_value="0.05"/>
<variable units="dimensionless" name="theta_R" initial_value="0.012"/>
<variable units="mM" name="K_RyR" initial_value="41e-3"/>
<variable units="mM" name="K_L" initial_value="0.22e-3"/>
<variable units="dimensionless" name="a" initial_value="0.0625"/>
<variable units="dimensionless" name="b" initial_value="14"/>
<variable units="dimensionless" name="c" initial_value="0.01"/>
<variable units="dimensionless" name="d" initial_value="100"/>
<variable units="dimensionless" name="expVL"/>
<variable units="per_ms" public_interface="out" name="alpha_p"/>
<variable units="per_ms" public_interface="out" name="alpha_m"/>
<variable units="per_ms" public_interface="out" name="beta_poc"/>
<variable units="per_ms" public_interface="out" name="beta_pcc"/>
<variable units="per_ms" public_interface="out" name="beta_m"/>
<variable units="per_ms" public_interface="out" name="epsilon_pco"/>
<variable units="per_ms" public_interface="out" name="epsilon_pcc"/>
<variable units="per_ms" public_interface="out" name="epsilon_m"/>
<variable units="per_ms" public_interface="out" name="mu_poc"/>
<variable units="per_ms" public_interface="out" name="mu_pcc"/>
<variable units="per_ms" public_interface="out" name="mu_moc"/>
<variable units="per_ms" public_interface="out" name="mu_mcc"/>
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</apply>
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</apply>
</apply>
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<apply>
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<ci>beta_pcc</ci>
<apply>
<divide/>
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<power/>
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<divide/>
<ci>J_R</ci>
<ci>g_D</ci>
</apply>
<apply>
<divide/>
<apply>
<times/>
<apply>
<divide/>
<ci>J_L</ci>
<ci>g_D</ci>
</apply>
<ci>FVRT_Ca</ci>
</apply>
<apply>
<minus/>
<cn cellml:units="dimensionless">1</cn>
<apply>
<exp/>
<apply>
<minus/>
<ci>FVRT_Ca</ci>
</apply>
</apply>
</apply>
</apply>
</apply>
</apply>
<apply>
<gt/>
<apply>
<abs/>
<ci>FVRT_Ca</ci>
</apply>
<cn cellml:units="dimensionless">0.000000001</cn>
</apply>
</piece>
<otherwise>
<apply>
<divide/>
<apply>
<plus/>
<ci>Ca_i</ci>
<apply>
<times/>
<apply>
<divide/>
<ci>J_R</ci>
<ci>g_D</ci>
</apply>
<ci>Ca_SR</ci>
</apply>
<apply>
<times/>
<apply>
<divide/>
<ci>J_L</ci>
<ci>g_D</ci>
</apply>
<ci>Ca_o</ci>
</apply>
</apply>
<apply>
<plus/>
<cn cellml:units="dimensionless">1</cn>
<apply>
<divide/>
<ci>J_R</ci>
<ci>g_D</ci>
</apply>
<apply>
<divide/>
<ci>J_L</ci>
<ci>g_D</ci>
</apply>
</apply>
</apply>
</otherwise>
</piecewise>
</apply>
</math>
</component>
<component name="LCC_and_RyR_fluxes">
<variable units="um3_per_ms" public_interface="in" name="g_D"/>
<variable units="um3_per_ms" public_interface="in" name="J_R"/>
<variable units="um3_per_ms" public_interface="in" name="J_L"/>
<variable units="mM" public_interface="in" name="Ca_i"/>
<variable units="mM" public_interface="in" name="Ca_SR"/>
<variable units="mM" public_interface="in" name="Ca_o"/>
<variable units="dimensionless" public_interface="in" name="FVRT_Ca"/>
<variable units="um3_mM_per_ms" public_interface="out" name="J_Loo"/>
<variable units="um3_mM_per_ms" public_interface="out" name="J_Loc"/>
<variable units="um3_mM_per_ms" public_interface="out" name="J_Rco"/>
<variable units="um3_mM_per_ms" public_interface="out" name="J_Roo"/>
<math xmlns="http://www.w3.org/1998/Math/MathML">
<apply>
<eq/>
<ci>J_Rco</ci>
<apply>
<divide/>
<apply>
<times/>
<ci>J_R</ci>
<apply>
<minus/>
<ci>Ca_SR</ci>
<ci>Ca_i</ci>
</apply>
</apply>
<apply>
<plus/>
<cn cellml:units="dimensionless">1</cn>
<apply>
<divide/>
<ci>J_R</ci>
<ci>g_D</ci>
</apply>
</apply>
</apply>
</apply>
<apply>
<eq/>
<ci>J_Roo</ci>
<piecewise>
<piece>
<apply>
<divide/>
<apply>
<times/>
<ci>J_R</ci>
<apply>
<plus/>
<apply>
<minus/>
<ci>Ca_SR</ci>
<ci>Ca_i</ci>
</apply>
<apply>
<times/>
<apply>
<divide/>
<apply>
<times/>
<apply>
<divide/>
<ci>J_L</ci>
<ci>g_D</ci>
</apply>
<ci>FVRT_Ca</ci>
</apply>
<apply>
<minus/>
<cn cellml:units="dimensionless">1</cn>
<apply>
<exp/>
<apply>
<minus/>
<ci>FVRT_Ca</ci>
</apply>
</apply>
</apply>
</apply>
<apply>
<minus/>
<ci>Ca_SR</ci>
<apply>
<times/>
<ci>Ca_o</ci>
<apply>
<exp/>
<apply>
<minus/>
<ci>FVRT_Ca</ci>
</apply>
</apply>
</apply>
</apply>
</apply>
</apply>
</apply>
<apply>
<plus/>
<cn cellml:units="dimensionless">1</cn>
<apply>
<divide/>
<ci>J_R</ci>
<ci>g_D</ci>
</apply>
<apply>
<divide/>
<apply>
<times/>
<apply>
<divide/>
<ci>J_L</ci>
<ci>g_D</ci>
</apply>
<ci>FVRT_Ca</ci>
</apply>
<apply>
<minus/>
<cn cellml:units="dimensionless">1</cn>
<apply>
<exp/>
<apply>
<minus/>
<ci>FVRT_Ca</ci>
</apply>
</apply>
</apply>
</apply>
</apply>
</apply>
<apply>
<gt/>
<apply>
<abs/>
<ci>FVRT_Ca</ci>
</apply>
<cn cellml:units="dimensionless">0.00001</cn>
</apply>
</piece>
<otherwise>
<apply>
<divide/>
<apply>
<times/>
<ci>J_R</ci>
<apply>
<plus/>
<apply>
<minus/>
<ci>Ca_SR</ci>
<ci>Ca_i</ci>
</apply>
<apply>
<times/>
<apply>
<divide/>
<apply>
<times/>
<apply>
<divide/>
<ci>J_L</ci>
<ci>g_D</ci>
</apply>
<cn cellml:units="dimensionless">0.00001</cn>
</apply>
<apply>
<minus/>
<cn cellml:units="dimensionless">1</cn>
<apply>
<exp/>
<apply>
<minus/>
<cn cellml:units="dimensionless">0.00001</cn>
</apply>
</apply>
</apply>
</apply>
<apply>
<minus/>
<ci>Ca_SR</ci>
<apply>
<times/>
<ci>Ca_o</ci>
<apply>
<exp/>
<apply>
<minus/>
<cn cellml:units="dimensionless">0.00001</cn>
</apply>
</apply>
</apply>
</apply>
</apply>
</apply>
</apply>
<apply>
<plus/>
<cn cellml:units="dimensionless">1</cn>
<apply>
<divide/>
<ci>J_R</ci>
<ci>g_D</ci>
</apply>
<apply>
<divide/>
<apply>
<times/>
<apply>
<divide/>
<ci>J_L</ci>
<ci>g_D</ci>
</apply>
<cn cellml:units="dimensionless">0.00001</cn>
</apply>
<apply>
<minus/>
<cn cellml:units="dimensionless">1</cn>
<apply>
<exp/>
<apply>
<minus/>
<cn cellml:units="dimensionless">0.00001</cn>
</apply>
</apply>
</apply>
</apply>
</apply>
</apply>
</otherwise>
</piecewise>
</apply>
<apply>
<eq/>
<ci>J_Loc</ci>
<piecewise>
<piece>
<apply>
<divide/>
<apply>
<times/>
<apply>
<divide/>
<apply>
<times/>
<ci>J_L</ci>
<ci>FVRT_Ca</ci>
</apply>
<apply>
<minus/>
<cn cellml:units="dimensionless">1</cn>
<apply>
<exp/>
<apply>
<minus/>
<ci>FVRT_Ca</ci>
</apply>
</apply>
</apply>
</apply>
<apply>
<minus/>
<apply>
<times/>
<ci>Ca_o</ci>
<apply>
<exp/>
<apply>
<minus/>
<ci>FVRT_Ca</ci>
</apply>
</apply>
</apply>
<ci>Ca_i</ci>
</apply>
</apply>
<apply>
<plus/>
<cn cellml:units="dimensionless">1</cn>
<apply>
<divide/>
<apply>
<times/>
<apply>
<divide/>
<ci>J_L</ci>
<ci>g_D</ci>
</apply>
<ci>FVRT_Ca</ci>
</apply>
<apply>
<minus/>
<cn cellml:units="dimensionless">1</cn>
<apply>
<exp/>
<apply>
<minus/>
<ci>FVRT_Ca</ci>
</apply>
</apply>
</apply>
</apply>
</apply>
</apply>
<apply>
<gt/>
<apply>
<abs/>
<ci>FVRT_Ca</ci>
</apply>
<cn cellml:units="dimensionless">0.00001</cn>
</apply>
</piece>
<otherwise>
<apply>
<divide/>
<apply>
<times/>
<apply>
<divide/>
<apply>
<times/>
<ci>J_L</ci>
<cn cellml:units="dimensionless">0.00001</cn>
</apply>
<apply>
<minus/>
<cn cellml:units="dimensionless">1</cn>
<apply>
<exp/>
<apply>
<minus/>
<cn cellml:units="dimensionless">0.00001</cn>
</apply>
</apply>
</apply>
</apply>
<apply>
<minus/>
<apply>
<times/>
<ci>Ca_o</ci>
<apply>
<exp/>
<apply>
<minus/>
<cn cellml:units="dimensionless">0.00001</cn>
</apply>
</apply>
</apply>
<ci>Ca_i</ci>
</apply>
</apply>
<apply>
<plus/>
<cn cellml:units="dimensionless">1</cn>
<apply>
<divide/>
<apply>
<times/>
<apply>
<divide/>
<ci>J_L</ci>
<ci>g_D</ci>
</apply>
<cn cellml:units="dimensionless">0.00001</cn>
</apply>
<apply>
<minus/>
<cn cellml:units="dimensionless">1</cn>
<apply>
<exp/>
<apply>
<minus/>
<cn cellml:units="dimensionless">0.00001</cn>
</apply>
</apply>
</apply>
</apply>
</apply>
</apply>
</otherwise>
</piecewise>
</apply>
<apply>
<eq/>
<ci>J_Loo</ci>
<piecewise>
<piece>
<apply>
<divide/>
<apply>
<times/>
<apply>
<divide/>
<apply>
<times/>
<ci>J_L</ci>
<ci>FVRT_Ca</ci>
</apply>
<apply>
<minus/>
<cn cellml:units="dimensionless">1</cn>
<apply>
<exp/>
<apply>
<minus/>
<ci>FVRT_Ca</ci>
</apply>
</apply>
</apply>
</apply>
<apply>
<plus/>
<apply>
<minus/>
<apply>
<times/>
<ci>Ca_o</ci>
<apply>
<exp/>
<apply>
<minus/>
<ci>FVRT_Ca</ci>
</apply>
</apply>
</apply>
<ci>Ca_i</ci>
</apply>
<apply>
<times/>
<apply>
<divide/>
<ci>J_R</ci>
<ci>g_D</ci>
</apply>
<apply>
<minus/>
<apply>
<times/>
<ci>Ca_o</ci>
<apply>
<exp/>
<apply>
<minus/>
<ci>FVRT_Ca</ci>
</apply>
</apply>
</apply>
<ci>Ca_SR</ci>
</apply>
</apply>
</apply>
</apply>
<apply>
<plus/>
<cn cellml:units="dimensionless">1</cn>
<apply>
<divide/>
<ci>J_R</ci>
<ci>g_D</ci>
</apply>
<apply>
<divide/>
<apply>
<times/>
<apply>
<divide/>
<ci>J_L</ci>
<ci>g_D</ci>
</apply>
<ci>FVRT_Ca</ci>
</apply>
<apply>
<minus/>
<cn cellml:units="dimensionless">1</cn>
<apply>
<exp/>
<ci>FVRT_Ca</ci>
</apply>
</apply>
</apply>
</apply>
</apply>
<apply>
<gt/>
<apply>
<abs/>
<ci>FVRT_Ca</ci>
</apply>
<cn cellml:units="dimensionless">0.00001</cn>
</apply>
</piece>
<otherwise>
<apply>
<divide/>
<apply>
<times/>
<apply>
<divide/>
<apply>
<times/>
<ci>J_L</ci>
<cn cellml:units="dimensionless">0.00001</cn>
</apply>
<apply>
<minus/>
<cn cellml:units="dimensionless">1</cn>
<apply>
<exp/>
<apply>
<minus/>
<cn cellml:units="dimensionless">0.00001</cn>
</apply>
</apply>
</apply>
</apply>
<apply>
<plus/>
<apply>
<minus/>
<apply>
<times/>
<ci>Ca_o</ci>
<apply>
<exp/>
<apply>
<minus/>
<cn cellml:units="dimensionless">0.00001</cn>
</apply>
</apply>
</apply>
<ci>Ca_i</ci>
</apply>
<apply>
<times/>
<apply>
<divide/>
<ci>J_R</ci>
<ci>g_D</ci>
</apply>
<apply>
<minus/>
<apply>
<times/>
<ci>Ca_o</ci>
<apply>
<exp/>
<apply>
<minus/>
<cn cellml:units="dimensionless">0.00001</cn>
</apply>
</apply>
</apply>
<ci>Ca_SR</ci>
</apply>
</apply>
</apply>
</apply>
<apply>
<plus/>
<cn cellml:units="dimensionless">1</cn>
<apply>
<divide/>
<ci>J_R</ci>
<ci>g_D</ci>
</apply>
<apply>
<divide/>
<apply>
<times/>
<apply>
<divide/>
<ci>J_L</ci>
<ci>g_D</ci>
</apply>
<cn cellml:units="dimensionless">0.00001</cn>
</apply>
<apply>
<minus/>
<cn cellml:units="dimensionless">1</cn>
<apply>
<exp/>
<apply>
<minus/>
<cn cellml:units="dimensionless">0.00001</cn>
</apply>
</apply>
</apply>
</apply>
</apply>
</apply>
</otherwise>
</piecewise>
</apply>
</math>
</component>
<component name="CaRU_states">
<variable units="per_ms" public_interface="in" name="alpha_p"/>
<variable units="per_ms" public_interface="in" name="alpha_m"/>
<variable units="per_ms" public_interface="in" name="beta_pcc"/>
<variable units="per_ms" public_interface="in" name="beta_poc"/>
<variable units="per_ms" public_interface="in" name="beta_m"/>
<variable units="per_ms3" name="denom"/>
<variable units="dimensionless" public_interface="out" name="y_oc"/>
<variable units="dimensionless" public_interface="out" name="y_co"/>
<variable units="dimensionless" public_interface="out" name="y_oo"/>
<variable units="dimensionless" public_interface="out" name="y_cc"/>
<variable units="dimensionless" public_interface="out" name="y_ci"/>
<variable units="dimensionless" public_interface="out" name="y_oi"/>
<variable units="dimensionless" public_interface="out" name="y_ic"/>
<variable units="dimensionless" public_interface="out" name="y_io"/>
<variable units="dimensionless" public_interface="out" name="y_ii"/>
<math xmlns="http://www.w3.org/1998/Math/MathML">
<apply>
<eq/>
<ci>denom</ci>
<apply>
<times/>
<apply>
<plus/>
<ci>alpha_p</ci>
<ci>alpha_m</ci>
</apply>
<apply>
<plus/>
<apply>
<times/>
<apply>
<plus/>
<ci>alpha_m</ci>
<ci>beta_m</ci>
<ci>beta_poc</ci>
</apply>
<apply>
<plus/>
<ci>beta_m</ci>
<ci>beta_pcc</ci>
</apply>
</apply>
<apply>
<times/>
<ci>alpha_p</ci>
<apply>
<plus/>
<ci>beta_m</ci>
<ci>beta_poc</ci>
</apply>
</apply>
</apply>
</apply>
</apply>
<apply>
<eq/>
<ci>y_oc</ci>
<apply>
<divide/>
<apply>
<times/>
<ci>alpha_p</ci>
<ci>beta_m</ci>
<apply>
<plus/>
<ci>alpha_p</ci>
<ci>alpha_m</ci>
<ci>beta_m</ci>
<ci>beta_pcc</ci>
</apply>
</apply>
<ci>denom</ci>
</apply>
</apply>
<apply>
<eq/>
<ci>y_co</ci>
<apply>
<divide/>
<apply>
<times/>
<ci>alpha_m</ci>
<apply>
<plus/>
<apply>
<times/>
<ci>beta_pcc</ci>
<apply>
<plus/>
<ci>alpha_m</ci>
<ci>beta_m</ci>
<ci>beta_poc</ci>
</apply>
</apply>
<apply>
<times/>
<ci>beta_poc</ci>
<ci>alpha_p</ci>
</apply>
</apply>
</apply>
<ci>denom</ci>
</apply>
</apply>
<apply>
<eq/>
<ci>y_oo</ci>
<apply>
<divide/>
<apply>
<times/>
<ci>alpha_p</ci>
<apply>
<plus/>
<apply>
<times/>
<ci>beta_poc</ci>
<apply>
<plus/>
<ci>alpha_p</ci>
<ci>beta_m</ci>
<ci>beta_pcc</ci>
</apply>
</apply>
<apply>
<times/>
<ci>beta_pcc</ci>
<ci>alpha_m</ci>
</apply>
</apply>
</apply>
<ci>denom</ci>
</apply>
</apply>
<apply>
<eq/>
<ci>y_cc</ci>
<apply>
<divide/>
<apply>
<times/>
<ci>alpha_m</ci>
<ci>beta_m</ci>
<apply>
<plus/>
<ci>alpha_m</ci>
<ci>alpha_p</ci>
<ci>beta_m</ci>
<ci>beta_poc</ci>
</apply>
</apply>
<ci>denom</ci>
</apply>
</apply>
<apply>
<eq/>
<ci>y_ci</ci>
<apply>
<divide/>
<ci>alpha_m</ci>
<apply>
<plus/>
<ci>alpha_p</ci>
<ci>alpha_m</ci>
</apply>
</apply>
</apply>
<apply>
<eq/>
<ci>y_oi</ci>
<apply>
<divide/>
<ci>alpha_p</ci>
<apply>
<plus/>
<ci>alpha_p</ci>
<ci>alpha_m</ci>
</apply>
</apply>
</apply>
<apply>
<eq/>
<ci>y_ic</ci>
<apply>
<divide/>
<ci>beta_m</ci>
<apply>
<plus/>
<ci>beta_pcc</ci>
<ci>beta_m</ci>
</apply>
</apply>
</apply>
<apply>
<eq/>
<ci>y_io</ci>
<apply>
<divide/>
<ci>beta_pcc</ci>
<apply>
<plus/>
<ci>beta_pcc</ci>
<ci>beta_m</ci>
</apply>
</apply>
</apply>
<apply>
<eq/>
<ci>y_ii</ci>
<apply>
<minus/>
<apply>
<minus/>
<apply>
<minus/>
<apply>
<minus/>
<apply>
<minus/>
<apply>
<minus/>
<apply>
<minus/>
<apply>
<minus/>
<cn cellml:units="dimensionless">1</cn>
<ci>y_oc</ci>
</apply>
<ci>y_co</ci>
</apply>
<ci>y_oo</ci>
</apply>
<ci>y_cc</ci>
</apply>
<ci>y_ci</ci>
</apply>
<ci>y_ic</ci>
</apply>
<ci>y_oi</ci>
</apply>
<ci>y_io</ci>
</apply>
</apply>
</math>
</component>
<component name="CaRU_reduced_states">
<variable units="dimensionless" public_interface="in" name="y_oc"/>
<variable units="dimensionless" public_interface="in" name="y_cc"/>
<variable units="dimensionless" public_interface="in" name="y_co"/>
<variable units="per_ms" public_interface="in" name="alpha_p"/>
<variable units="per_ms" public_interface="in" name="alpha_m"/>
<variable units="per_ms" public_interface="in" name="beta_pcc"/>
<variable units="per_ms" public_interface="in" name="beta_m"/>
<variable units="per_ms" public_interface="in" name="epsilon_pco"/>
<variable units="per_ms" public_interface="in" name="epsilon_pcc"/>
<variable units="per_ms" public_interface="in" name="epsilon_m"/>
<variable units="per_ms" public_interface="in" name="mu_poc"/>
<variable units="per_ms" public_interface="in" name="mu_pcc"/>
<variable units="per_ms" public_interface="in" name="mu_moc"/>
<variable units="per_ms" public_interface="in" name="mu_mcc"/>
<variable units="per_ms" public_interface="out" name="r_1"/>
<variable units="per_ms" public_interface="out" name="r_2"/>
<variable units="per_ms" public_interface="out" name="r_3"/>
<variable units="per_ms" public_interface="out" name="r_4"/>
<variable units="per_ms" public_interface="out" name="r_5"/>
<variable units="per_ms" public_interface="out" name="r_6"/>
<variable units="per_ms" public_interface="out" name="r_7"/>
<variable units="per_ms" public_interface="out" name="r_8"/>
<variable units="dimensionless" public_interface="out" name="z_1" initial_value="0.98859"/>
<variable units="dimensionless" public_interface="out" name="z_2" initial_value="0.0087302"/>
<variable units="dimensionless" public_interface="out" name="z_3" initial_value="0.0026566"/>
<variable units="dimensionless" public_interface="out" name="z_4"/>
<variable units="ms" public_interface="in" name="time"/>
<math xmlns="http://www.w3.org/1998/Math/MathML">
<apply>
<eq/>
<ci>r_1</ci>
<apply>
<plus/>
<apply>
<times/>
<ci>y_oc</ci>
<ci>mu_poc</ci>
</apply>
<apply>
<times/>
<ci>y_cc</ci>
<ci>mu_pcc</ci>
</apply>
</apply>
</apply>
<apply>
<eq/>
<ci>r_2</ci>
<apply>
<divide/>
<apply>
<plus/>
<apply>
<times/>
<ci>alpha_p</ci>
<ci>mu_moc</ci>
</apply>
<apply>
<times/>
<ci>alpha_m</ci>
<ci>mu_mcc</ci>
</apply>
</apply>
<apply>
<plus/>
<ci>alpha_p</ci>
<ci>alpha_m</ci>
</apply>
</apply>
</apply>
<apply>
<eq/>
<ci>r_3</ci>
<apply>
<divide/>
<apply>
<times/>
<ci>beta_m</ci>
<ci>mu_pcc</ci>
</apply>
<apply>
<plus/>
<ci>beta_m</ci>
<ci>beta_pcc</ci>
</apply>
</apply>
</apply>
<apply>
<eq/>
<ci>r_4</ci>
<ci>mu_mcc</ci>
</apply>
<apply>
<eq/>
<ci>r_5</ci>
<apply>
<plus/>
<apply>
<times/>
<ci>y_co</ci>
<ci>epsilon_pco</ci>
</apply>
<apply>
<times/>
<ci>y_cc</ci>
<ci>epsilon_pcc</ci>
</apply>
</apply>
</apply>
<apply>
<eq/>
<ci>r_6</ci>
<ci>epsilon_m</ci>
</apply>
<apply>
<eq/>
<ci>r_7</ci>
<apply>
<divide/>
<apply>
<times/>
<ci>alpha_m</ci>
<ci>epsilon_pcc</ci>
</apply>
<apply>
<plus/>
<ci>alpha_p</ci>
<ci>alpha_m</ci>
</apply>
</apply>
</apply>
<apply>
<eq/>
<ci>r_8</ci>
<ci>epsilon_m</ci>
</apply>
<apply>
<eq/>
<ci>z_4</ci>
<apply>
<minus/>
<apply>
<minus/>
<apply>
<minus/>
<cn cellml:units="dimensionless">1</cn>
<ci>z_1</ci>
</apply>
<ci>z_2</ci>
</apply>
<ci>z_3</ci>
</apply>
</apply>
<apply>
<eq/>
<apply>
<diff/>
<bvar>
<ci>time</ci>
</bvar>
<ci>z_1</ci>
</apply>
<apply>
<plus/>
<apply>
<times/>
<apply>
<minus/>
<apply>
<plus/>
<ci>r_1</ci>
<ci>r_5</ci>
</apply>
</apply>
<ci>z_1</ci>
</apply>
<apply>
<times/>
<ci>r_2</ci>
<ci>z_2</ci>
</apply>
<apply>
<times/>
<ci>r_6</ci>
<ci>z_3</ci>
</apply>
</apply>
</apply>
<apply>
<eq/>
<apply>
<diff/>
<bvar>
<ci>time</ci>
</bvar>
<ci>z_2</ci>
</apply>
<apply>
<plus/>
<apply>
<minus/>
<apply>
<times/>
<ci>r_1</ci>
<ci>z_1</ci>
</apply>
<apply>
<times/>
<apply>
<plus/>
<ci>r_2</ci>
<ci>r_7</ci>
</apply>
<ci>z_2</ci>
</apply>
</apply>
<apply>
<times/>
<ci>r_8</ci>
<ci>z_4</ci>
</apply>
</apply>
</apply>
<apply>
<eq/>
<apply>
<diff/>
<bvar>
<ci>time</ci>
</bvar>
<ci>z_3</ci>
</apply>
<apply>
<plus/>
<apply>
<minus/>
<apply>
<times/>
<ci>r_5</ci>
<ci>z_1</ci>
</apply>
<apply>
<times/>
<apply>
<plus/>
<ci>r_6</ci>
<ci>r_3</ci>
</apply>
<ci>z_3</ci>
</apply>
</apply>
<apply>
<times/>
<ci>r_4</ci>
<ci>z_4</ci>
</apply>
</apply>
</apply>
</math>
</component>
<component name="RyR_current">
<variable units="dimensionless" public_interface="in" name="y_oo"/>
<variable units="dimensionless" public_interface="in" name="y_co"/>
<variable units="dimensionless" public_interface="in" name="y_oc"/>
<variable units="per_ms" public_interface="in" name="beta_pcc"/>
<variable units="per_ms" public_interface="in" name="beta_m"/>
<variable units="um3_mM_per_ms" public_interface="in" name="J_Roo"/>
<variable units="um3_mM_per_ms" public_interface="in" name="J_Rco"/>
<variable units="dimensionless" public_interface="in" name="z_1"/>
<variable units="dimensionless" public_interface="in" name="z_3"/>
<variable units="um3" public_interface="in" name="V_myo"/>
<variable units="dimensionless" public_interface="in" name="N"/>
<variable units="um3_mM_per_ms" public_interface="out" name="J_R1"/>
<variable units="um3_mM_per_ms" public_interface="out" name="J_R3"/>
<variable units="mM_per_ms" public_interface="out" name="I_RyR"/>
<math xmlns="http://www.w3.org/1998/Math/MathML">
<apply>
<eq/>
<ci>J_R1</ci>
<apply>
<plus/>
<apply>
<times/>
<ci>y_oo</ci>
<ci>J_Roo</ci>
</apply>
<apply>
<times/>
<ci>J_Rco</ci>
<ci>y_co</ci>
</apply>
</apply>
</apply>
<apply>
<eq/>
<ci>J_R3</ci>
<apply>
<divide/>
<apply>
<times/>
<ci>J_Rco</ci>
<ci>beta_pcc</ci>
</apply>
<apply>
<plus/>
<ci>beta_m</ci>
<ci>beta_pcc</ci>
</apply>
</apply>
</apply>
<apply>
<eq/>
<ci>I_RyR</ci>
<apply>
<divide/>
<apply>
<times/>
<apply>
<plus/>
<apply>
<times/>
<ci>z_1</ci>
<ci>J_R1</ci>
</apply>
<apply>
<times/>
<ci>z_3</ci>
<ci>J_R3</ci>
</apply>
</apply>
<ci>N</ci>
</apply>
<ci>V_myo</ci>
</apply>
</apply>
</math>
</component>
<component name="LCC_current">
<variable units="dimensionless" public_interface="in" name="y_oo"/>
<variable units="dimensionless" public_interface="in" name="y_oc"/>
<variable units="per_ms" public_interface="in" name="alpha_p"/>
<variable units="per_ms" public_interface="in" name="alpha_m"/>
<variable units="um3_mM_per_ms" public_interface="in" name="J_Loo"/>
<variable units="um3_mM_per_ms" public_interface="in" name="J_Loc"/>
<variable units="dimensionless" public_interface="in" name="z_1"/>
<variable units="dimensionless" public_interface="in" name="z_2"/>
<variable units="um3" public_interface="in" name="V_myo"/>
<variable units="dimensionless" public_interface="in" name="N"/>
<variable units="um3_mM_per_ms" public_interface="out" name="J_L1"/>
<variable units="um3_mM_per_ms" public_interface="out" name="J_L2"/>
<variable units="mM_per_ms" public_interface="out" name="I_LCC"/>
<math xmlns="http://www.w3.org/1998/Math/MathML">
<apply>
<eq/>
<ci>J_L1</ci>
<apply>
<plus/>
<apply>
<times/>
<ci>J_Loo</ci>
<ci>y_oo</ci>
</apply>
<apply>
<times/>
<ci>J_Loc</ci>
<ci>y_oc</ci>
</apply>
</apply>
</apply>
<apply>
<eq/>
<ci>J_L2</ci>
<apply>
<divide/>
<apply>
<times/>
<ci>J_Loc</ci>
<ci>alpha_p</ci>
</apply>
<apply>
<plus/>
<ci>alpha_p</ci>
<ci>alpha_m</ci>
</apply>
</apply>
</apply>
<apply>
<eq/>
<ci>I_LCC</ci>
<apply>
<divide/>
<apply>
<times/>
<apply>
<plus/>
<apply>
<times/>
<ci>z_1</ci>
<ci>J_L1</ci>
</apply>
<apply>
<times/>
<ci>z_2</ci>
<ci>J_L2</ci>
</apply>
</apply>
<ci>N</ci>
</apply>
<ci>V_myo</ci>
</apply>
</apply>
</math>
</component>
<component name="Na_Ca_Exchanger">
<variable units="dimensionless" public_interface="in" name="FVRT"/>
<variable units="mM" name="K_mNa" initial_value="87.5"/>
<variable units="mM" name="K_mCa" initial_value="1.38"/>
<variable units="dimensionless" name="eta" initial_value="0.35"/>
<variable units="dimensionless" name="k_sat" initial_value="0.1"/>
<variable units="mM_per_ms" name="g_NCX" initial_value="38.5e-3"/>
<variable units="mM" public_interface="in" name="Na_i"/>
<variable units="mM" public_interface="in" name="Na_o"/>
<variable units="mM" public_interface="in" name="Ca_i"/>
<variable units="mM" public_interface="in" name="Ca_o"/>
<variable units="mM_per_ms" public_interface="out" name="I_NaCa"/>
<math xmlns="http://www.w3.org/1998/Math/MathML">
<apply>
<eq/>
<ci>I_NaCa</ci>
<apply>
<divide/>
<apply>
<times/>
<ci>g_NCX</ci>
<apply>
<minus/>
<apply>
<times/>
<apply>
<exp/>
<apply>
<times/>
<ci>eta</ci>
<ci>FVRT</ci>
</apply>
</apply>
<apply>
<power/>
<ci>Na_i</ci>
<cn cellml:units="dimensionless">3</cn>
</apply>
<ci>Ca_o</ci>
</apply>
<apply>
<times/>
<apply>
<exp/>
<apply>
<times/>
<apply>
<minus/>
<ci>eta</ci>
<cn cellml:units="dimensionless">1</cn>
</apply>
<ci>FVRT</ci>
</apply>
</apply>
<apply>
<power/>
<ci>Na_o</ci>
<cn cellml:units="dimensionless">3</cn>
</apply>
<ci>Ca_i</ci>
</apply>
</apply>
</apply>
<apply>
<times/>
<apply>
<plus/>
<apply>
<power/>
<ci>Na_o</ci>
<cn cellml:units="dimensionless">3</cn>
</apply>
<apply>
<power/>
<ci>K_mNa</ci>
<cn cellml:units="dimensionless">3</cn>
</apply>
</apply>
<apply>
<plus/>
<ci>Ca_o</ci>
<ci>K_mCa</ci>
</apply>
<apply>
<plus/>
<cn cellml:units="dimensionless">1</cn>
<apply>
<times/>
<ci>k_sat</ci>
<apply>
<exp/>
<apply>
<times/>
<apply>
<minus/>
<ci>eta</ci>
<cn cellml:units="dimensionless">1</cn>
</apply>
<ci>FVRT</ci>
</apply>
</apply>
</apply>
</apply>
</apply>
</apply>
</apply>
</math>
</component>
<component name="SERCA">
<variable units="mM_per_ms" name="g_SERCA" initial_value="0.45e-3"/>
<variable units="mM" name="K_SERCA" initial_value="0.5e-3"/>
<variable units="mM_per_ms" public_interface="out" name="I_SERCA"/>
<variable units="mM" public_interface="in" name="Ca_i"/>
<math xmlns="http://www.w3.org/1998/Math/MathML">
<apply>
<eq/>
<ci>I_SERCA</ci>
<apply>
<divide/>
<apply>
<times/>
<ci>g_SERCA</ci>
<apply>
<power/>
<ci>Ca_i</ci>
<cn cellml:units="dimensionless">2</cn>
</apply>
</apply>
<apply>
<plus/>
<apply>
<power/>
<ci>K_SERCA</ci>
<cn cellml:units="dimensionless">2</cn>
</apply>
<apply>
<power/>
<ci>Ca_i</ci>
<cn cellml:units="dimensionless">2</cn>
</apply>
</apply>
</apply>
</apply>
</math>
</component>
<component name="Sarcolemmal_Ca_pump">
<variable units="mM_per_ms" name="g_pCa" initial_value="0.0035e-3"/>
<variable units="mM" name="K_mpCa" initial_value="0.5e-3"/>
<variable units="mM" public_interface="in" name="Ca_i"/>
<variable units="mM_per_ms" public_interface="out" name="I_pCa"/>
<math xmlns="http://www.w3.org/1998/Math/MathML">
<apply>
<eq/>
<ci>I_pCa</ci>
<apply>
<divide/>
<apply>
<times/>
<ci>g_pCa</ci>
<ci>Ca_i</ci>
</apply>
<apply>
<plus/>
<ci>K_mpCa</ci>
<ci>Ca_i</ci>
</apply>
</apply>
</apply>
</math>
</component>
<component name="Background_Ca_current">
<variable units="mV" public_interface="in" name="V"/>
<variable units="mJ_per_mole_K" public_interface="in" name="R"/>
<variable units="kelvin" public_interface="in" name="T"/>
<variable units="C_per_mole" public_interface="in" name="F"/>
<variable units="mM" public_interface="in" name="Ca_i"/>
<variable units="mM" public_interface="in" name="Ca_o"/>
<variable units="mV" public_interface="out" name="E_Ca"/>
<variable units="mM_per_mV_ms" name="g_CaB" initial_value="2.6875e-8"/>
<variable units="mM_per_ms" public_interface="out" name="I_CaB"/>
<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>Ca_o</ci>
<ci>Ca_i</ci>
</apply>
</apply>
</apply>
</apply>
<apply>
<eq/>
<ci>I_CaB</ci>
<apply>
<times/>
<ci>g_CaB</ci>
<apply>
<minus/>
<ci>E_Ca</ci>
<ci>V</ci>
</apply>
</apply>
</apply>
</math>
</component>
<component name="SR_Ca_leak_current">
<variable units="mM" public_interface="in" name="Ca_i"/>
<variable units="mM" public_interface="in" name="Ca_SR"/>
<variable units="per_ms" name="g_SRl" initial_value="1.8951e-5"/>
<variable units="mM_per_ms" public_interface="out" name="I_SR"/>
<math xmlns="http://www.w3.org/1998/Math/MathML">
<apply>
<eq/>
<ci>I_SR</ci>
<apply>
<times/>
<ci>g_SRl</ci>
<apply>
<minus/>
<ci>Ca_SR</ci>
<ci>Ca_i</ci>
</apply>
</apply>
</apply>
</math>
</component>
<component name="troponin_Ca_buffer">
<variable units="per_ms" name="k_m_TRPN" initial_value="0.04"/>
<variable units="per_mM_ms" name="k_p_TRPN" initial_value="0.04e3"/>
<variable units="mM" name="B_TRPN" initial_value="70e-3"/>
<variable units="mM" public_interface="in" name="TRPN"/>
<variable units="mM" public_interface="in" name="Ca_i"/>
<variable units="mM_per_ms" public_interface="out" name="I_TRPN"/>
<math xmlns="http://www.w3.org/1998/Math/MathML">
<apply>
<eq/>
<ci>I_TRPN</ci>
<apply>
<minus/>
<apply>
<times/>
<ci>k_m_TRPN</ci>
<apply>
<minus/>
<ci>B_TRPN</ci>
<ci>TRPN</ci>
</apply>
</apply>
<apply>
<times/>
<ci>k_p_TRPN</ci>
<ci>TRPN</ci>
<ci>Ca_i</ci>
</apply>
</apply>
</apply>
</math>
</component>
<component name="calmodulin_Ca_buffer">
<variable units="mM" name="k_CMDN" initial_value="2.382e-3"/>
<variable units="mM" name="B_CMDN" initial_value="50e-3"/>
<variable units="mM" public_interface="in" name="Ca_i"/>
<variable units="dimensionless" public_interface="out" name="beta_CMDN"/>
<math xmlns="http://www.w3.org/1998/Math/MathML">
<apply>
<eq/>
<ci>beta_CMDN</ci>
<apply>
<power/>
<apply>
<plus/>
<cn cellml:units="dimensionless">1</cn>
<apply>
<divide/>
<apply>
<times/>
<ci>k_CMDN</ci>
<ci>B_CMDN</ci>
</apply>
<apply>
<power/>
<apply>
<plus/>
<ci>k_CMDN</ci>
<ci>Ca_i</ci>
</apply>
<cn cellml:units="dimensionless">2</cn>
</apply>
</apply>
</apply>
<apply>
<minus/>
<cn cellml:units="dimensionless">1</cn>
</apply>
</apply>
</apply>
</math>
</component>
<component name="intracellular_ion_concentrations">
<variable units="mM" public_interface="out" name="Na_i" initial_value="10"/>
<variable units="mM" public_interface="out" cmeta:id="intracellular_ion_concentrations_Ca_i" name="Ca_i" initial_value="0.0001"/>
<variable units="mM" public_interface="out" name="Ca_SR" initial_value="700e-3"/>
<variable units="mM" public_interface="out" name="TRPN" initial_value="0.0636364"/>
<variable units="ms" public_interface="in" name="time"/>
<variable units="um3" public_interface="in" name="V_myo"/>
<variable units="um3" public_interface="in" name="V_SR"/>
<variable units="dimensionless" public_interface="in" name="beta_CMDN"/>
<variable units="mM_per_ms" public_interface="in" name="I_SERCA"/>
<variable units="mM_per_ms" public_interface="in" name="I_pCa"/>
<variable units="mM_per_ms" public_interface="in" name="I_CaB"/>
<variable units="mM_per_ms" public_interface="in" name="I_TRPN"/>
<variable units="mM_per_ms" public_interface="in" name="I_SR"/>
<variable units="mM_per_ms" public_interface="in" name="I_NaCa"/>
<variable units="mM_per_ms" public_interface="in" name="I_RyR"/>
<variable units="mM_per_ms" public_interface="in" name="I_LCC"/>
<variable units="mM" name="CaSR_plot" cmeta:id="intracellular_ion_concentrations_CaSR_plot"/>
<math xmlns="http://www.w3.org/1998/Math/MathML">
<apply>
<eq/>
<apply>
<diff/>
<bvar>
<ci>time</ci>
</bvar>
<ci>TRPN</ci>
</apply>
<ci>I_TRPN</ci>
</apply>
<apply>
<eq/>
<apply>
<diff/>
<bvar>
<ci>time</ci>
</bvar>
<ci>Ca_i</ci>
</apply>
<apply>
<times/>
<ci>beta_CMDN</ci>
<apply>
<plus/>
<apply>
<minus/>
<apply>
<plus/>
<apply>
<minus/>
<apply>
<plus/>
<ci>I_LCC</ci>
<ci>I_RyR</ci>
</apply>
<ci>I_SERCA</ci>
</apply>
<ci>I_SR</ci>
<ci>I_NaCa</ci>
</apply>
<ci>I_pCa</ci>
</apply>
<ci>I_CaB</ci>
<ci>I_TRPN</ci>
</apply>
</apply>
</apply>
<apply>
<eq/>
<apply>
<diff/>
<bvar>
<ci>time</ci>
</bvar>
<ci>Ca_SR</ci>
</apply>
<apply>
<times/>
<apply>
<divide/>
<ci>V_myo</ci>
<ci>V_SR</ci>
</apply>
<apply>
<minus/>
<apply>
<plus/>
<apply>
<minus/>
<ci>I_RyR</ci>
</apply>
<ci>I_SERCA</ci>
</apply>
<ci>I_SR</ci>
</apply>
</apply>
</apply>
<apply>
<eq/>
<ci>CaSR_plot</ci>
<apply>
<divide/>
<apply>
<times/>
<ci>Ca_SR</ci>
<ci>V_SR</ci>
</apply>
<ci>V_myo</ci>
</apply>
</apply>
</math>
</component>
<component name="extracellular_ion_concentrations">
<variable units="mM" public_interface="out" name="Na_o" initial_value="140"/>
<variable units="mM" public_interface="out" name="Ca_o" initial_value="1"/>
</component>
<group>
<relationship_ref relationship="containment"/>
<component_ref component="membrane">
<component_ref component="intracellular_ion_concentrations"/>
<component_ref component="extracellular_ion_concentrations"/>
<component_ref component="cell_geometry"/>
<component_ref component="CaRU">
<component_ref component="CaRU_Transitions"/>
<component_ref component="CaRU_states"/>
<component_ref component="CaRU_reduced_states"/>
<component_ref component="DS_Calcium_Concentrations"/>
<component_ref component="LCC_and_RyR_fluxes"/>
<component_ref component="RyR_current"/>
<component_ref component="LCC_current"/>
</component_ref>
<component_ref component="Na_Ca_Exchanger"/>
<component_ref component="SERCA"/>
<component_ref component="Sarcolemmal_Ca_pump"/>
<component_ref component="Background_Ca_current"/>
<component_ref component="SR_Ca_leak_current"/>
<component_ref component="troponin_Ca_buffer"/>
<component_ref component="calmodulin_Ca_buffer"/>
</component_ref>
</group>
<group>
<relationship_ref relationship="encapsulation"/>
<component_ref component="CaRU">
<component_ref component="CaRU_Transitions"/>
<component_ref component="CaRU_states"/>
<component_ref component="CaRU_reduced_states"/>
<component_ref component="DS_Calcium_Concentrations"/>
<component_ref component="LCC_and_RyR_fluxes"/>
<component_ref component="RyR_current"/>
<component_ref component="LCC_current"/>
</component_ref>
</group>
<connection>
<map_components component_2="membrane" component_1="environment"/>
<map_variables variable_2="time" variable_1="time"/>
</connection>
<connection>
<map_components component_2="CaRU" component_1="environment"/>
<map_variables variable_2="time" variable_1="time"/>
</connection>
<connection>
<map_components component_2="intracellular_ion_concentrations" component_1="environment"/>
<map_variables variable_2="time" variable_1="time"/>
</connection>
<connection>
<map_components component_2="CaRU" component_1="cell_geometry"/>
<map_variables variable_2="V_myo" variable_1="V_myo"/>
</connection>
<connection>
<map_components component_2="CaRU_reduced_states" component_1="CaRU"/>
<map_variables variable_2="time" variable_1="time"/>
</connection>
<connection>
<map_components component_2="LCC_and_RyR_fluxes" component_1="CaRU"/>
<map_variables variable_2="g_D" variable_1="g_D"/>
<map_variables variable_2="J_R" variable_1="J_R"/>
<map_variables variable_2="J_L" variable_1="J_L"/>
<map_variables variable_2="Ca_i" variable_1="Ca_i"/>
<map_variables variable_2="Ca_SR" variable_1="Ca_SR"/>
<map_variables variable_2="Ca_o" variable_1="Ca_o"/>
<map_variables variable_2="FVRT_Ca" variable_1="FVRT_Ca"/>
</connection>
<connection>
<map_components component_2="CaRU" component_1="membrane"/>
<map_variables variable_2="V" variable_1="V"/>
<map_variables variable_2="FVRT_Ca" variable_1="FVRT_Ca"/>
</connection>
<connection>
<map_components component_2="CaRU_Transitions" component_1="CaRU"/>
<map_variables variable_2="V" variable_1="V"/>
<map_variables variable_2="Ca_i" variable_1="Ca_i"/>
</connection>
<connection>
<map_components component_2="CaRU_states" component_1="CaRU_Transitions"/>
<map_variables variable_2="alpha_p" variable_1="alpha_p"/>
<map_variables variable_2="alpha_m" variable_1="alpha_m"/>
<map_variables variable_2="beta_pcc" variable_1="beta_pcc"/>
<map_variables variable_2="beta_poc" variable_1="beta_poc"/>
<map_variables variable_2="beta_m" variable_1="beta_m"/>
</connection>
<connection>
<map_components component_2="RyR_current" component_1="CaRU_Transitions"/>
<map_variables variable_2="beta_pcc" variable_1="beta_pcc"/>
<map_variables variable_2="beta_m" variable_1="beta_m"/>
</connection>
<connection>
<map_components component_2="LCC_current" component_1="CaRU_Transitions"/>
<map_variables variable_2="alpha_p" variable_1="alpha_p"/>
<map_variables variable_2="alpha_m" variable_1="alpha_m"/>
</connection>
<connection>
<map_components component_2="RyR_current" component_1="CaRU_states"/>
<map_variables variable_2="y_oo" variable_1="y_oo"/>
<map_variables variable_2="y_co" variable_1="y_co"/>
<map_variables variable_2="y_oc" variable_1="y_oc"/>
</connection>
<connection>
<map_components component_2="LCC_current" component_1="CaRU_states"/>
<map_variables variable_2="y_oo" variable_1="y_oo"/>
<map_variables variable_2="y_oc" variable_1="y_oc"/>
</connection>
<connection>
<map_components component_2="RyR_current" component_1="LCC_and_RyR_fluxes"/>
<map_variables variable_2="J_Roo" variable_1="J_Roo"/>
<map_variables variable_2="J_Rco" variable_1="J_Rco"/>
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