<?xml version='1.0' encoding='utf-8'?>
<!-- FILE : sachse_model_2007.xml
CREATED : 27th August 2007
LAST MODIFIED : 27th August 2007
AUTHOR : Catherine Lloyd
Bioengineering Institute
The University of Auckland
MODEL STATUS : This model conforms to the CellML 1.1 Specification.
DESCRIPTION : This file contains a CellML description of Sachse, Moreno and Abildskov's 2007 mathematical model of the electrophysiology of fibroblasts and how they interact with myocytes.
CHANGES:
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<documentation xmlns="http://cellml.org/tmp-documentation">
<article>
<articleinfo>
<title>Electrophysiological Modeling of Fibroblasts and Their Interaction with Myocytes</title>
<author>
<firstname>Catherine</firstname>
<surname>Lloyd</surname>
<affiliation>
<shortaffil>Bioengineering Institute, University of Auckland</shortaffil>
</affiliation>
</author>
</articleinfo>
<section id="sec_status">
<title>Model Status</title>
<para>
This CellML version of the model runs in PCEnv, COR and JSim to recreate the results in the Figure 7 of the publication. The CVode integrator needs to be used in Jsim to run this model. The units have been checked and are consistent, and we would like to thank Frank Sachse, the original model author, for his advice and assistance in getting the CellML version of this model working. This CellML model represents the coupled fibroblast-myocyte model, 1:1 ratio. This ratio can be changed by altering the value of the variable 'number_of_fibroblasts' in the component 'I_inter'.
</para>
</section>
<sect1 id="sec_structure">
<title>Model Structure</title>
<para>
Fibroblasts are the most abundant cell type present in the heart. They are arranged in the myocardium, as a three-dimensional network, where they are responsible for the secretion of extracellular matrix proteins, and also play a role in cardiac electrophysiology. Although fibroblasts themselves are electrically in-excitable, they can contribute to the electrophysiology of neighbouring myocytes through fibroblast-myocyte coupling. Although the electrical coupling of fibroblasts and myocytes has been demonstrated experimentally both in vivo and in vitro, the precise role of fibroblasts as electrical bridges between myocytes still remains to be defined.
</para>
<para>
In the paper described here, Frank Sachse, Alonso Moreno and J. A. Abildskov address this issue by presenting mathematical models of cellular and multi-cellular electrophysiology. A novel mathematical model of cardiac fibroblasts was developed on the basis of experimental data from whole cell patch clamp and polymerase chain reaction studies. This model was then applied, together with models of ventricular myocytes (which were based on the <ulink url="http://www.cellml.org/models/pandit_clark_giles_demir_2001_version07">Pandit <emphasis>et al.</emphasis> 2001 model</ulink> of the rat left ventricular myocyte), to determine the electrophysiological effects of heterogeneous electrical coupling of cells.
</para>
<informalfigure float="0" id="fig_reaction_diagram">
<mediaobject>
<imageobject>
<objectinfo>
<title>model diagram</title>
</objectinfo>
<imagedata fileref="sachse_coupled_2007.png"/>
</imageobject>
</mediaobject>
<caption>Schematic diagram of the fibroblast cell model. A Markovian model for the time and voltage dependent outward current (I<subscript>SHkr</subscript>) is embedded within an electrophysiological cell model. The ion channel has six different states; five closed states (C0-4) and one open state (O)</caption>
</informalfigure>
<para>
The original paper reference is cited below:
</para>
<para>
Electrophysiological Modeling of Fibroblasts and Their Interaction with Myocytes, F.B. Sachse, A.P. Moreno, and J.A. Abildskov, 2008, Jan<emphasis>Annals of Biomedical Engineering</emphasis>
<ulink url="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=AbstractPlus&list_uids=17999190&query_hl=1&itool=pubmed_docsum">PubMed ID: 17999190</ulink>
</para>
</sect1>
</article>
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<variable units="millivolt" public_interface="in" name="V"/>
<variable units="second" public_interface="in" name="time"/>
<math xmlns="http://www.w3.org/1998/Math/MathML">
<apply>
<eq/>
<ci>d_infinity</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">15.3</cn>
</apply>
<apply>
<minus/>
<cn cellml:units="millivolt">5</cn>
</apply>
</apply>
</apply>
</apply>
</apply>
</apply>
<apply>
<eq/>
<ci>tau_d</ci>
<apply>
<plus/>
<apply>
<times/>
<cn cellml:units="second">0.00305</cn>
<apply>
<exp/>
<apply>
<times/>
<apply>
<minus/>
<cn cellml:units="per_millivolt2">0.0045</cn>
</apply>
<apply>
<power/>
<apply>
<plus/>
<ci>V</ci>
<cn cellml:units="millivolt">7</cn>
</apply>
<cn cellml:units="dimensionless">2</cn>
</apply>
</apply>
</apply>
</apply>
<apply>
<times/>
<cn cellml:units="second">0.00105</cn>
<apply>
<exp/>
<apply>
<times/>
<apply>
<minus/>
<cn cellml:units="per_millivolt2">0.002</cn>
</apply>
<apply>
<power/>
<apply>
<minus/>
<ci>V</ci>
<cn cellml:units="millivolt">18</cn>
</apply>
<cn cellml:units="dimensionless">2</cn>
</apply>
</apply>
</apply>
</apply>
<cn cellml:units="second">0.00025</cn>
</apply>
</apply>
<apply>
<eq/>
<apply>
<diff/>
<bvar>
<ci>time</ci>
</bvar>
<ci>d</ci>
</apply>
<apply>
<divide/>
<apply>
<minus/>
<ci>d_infinity</ci>
<ci>d</ci>
</apply>
<ci>tau_d</ci>
</apply>
</apply>
</math>
</component>
<component name="L_type_Ca_channel_f_11_gate">
<variable units="dimensionless" public_interface="out" name="f_11" initial_value="0.9999529"/>
<variable units="dimensionless" name="f_11_infinity"/>
<variable units="second" name="tau_f_11"/>
<variable units="millivolt" public_interface="in" name="V"/>
<variable units="second" public_interface="in" name="time"/>
<math xmlns="http://www.w3.org/1998/Math/MathML">
<apply>
<eq/>
<ci>f_11_infinity</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">26.7</cn>
</apply>
<cn cellml:units="millivolt">5.4</cn>
</apply>
</apply>
</apply>
</apply>
</apply>
<apply>
<eq/>
<ci>tau_f_11</ci>
<apply>
<plus/>
<apply>
<times/>
<cn cellml:units="second">0.105</cn>
<apply>
<exp/>
<apply>
<minus/>
<apply>
<power/>
<apply>
<divide/>
<apply>
<plus/>
<ci>V</ci>
<cn cellml:units="millivolt">45</cn>
</apply>
<cn cellml:units="millivolt">12</cn>
</apply>
<cn cellml:units="dimensionless">2</cn>
</apply>
</apply>
</apply>
</apply>
<apply>
<divide/>
<cn cellml:units="second">0.04</cn>
<apply>
<plus/>
<cn cellml:units="dimensionless">1</cn>
<apply>
<exp/>
<apply>
<divide/>
<apply>
<plus/>
<apply>
<minus/>
<ci>V</ci>
</apply>
<cn cellml:units="millivolt">25</cn>
</apply>
<cn cellml:units="millivolt">25</cn>
</apply>
</apply>
</apply>
</apply>
<apply>
<divide/>
<cn cellml:units="second">0.015</cn>
<apply>
<plus/>
<cn cellml:units="dimensionless">1</cn>
<apply>
<exp/>
<apply>
<divide/>
<apply>
<plus/>
<ci>V</ci>
<cn cellml:units="millivolt">75</cn>
</apply>
<cn cellml:units="millivolt">25</cn>
</apply>
</apply>
</apply>
</apply>
<cn cellml:units="second">0.0017</cn>
</apply>
</apply>
<apply>
<eq/>
<apply>
<diff/>
<bvar>
<ci>time</ci>
</bvar>
<ci>f_11</ci>
</apply>
<apply>
<divide/>
<apply>
<minus/>
<ci>f_11_infinity</ci>
<ci>f_11</ci>
</apply>
<ci>tau_f_11</ci>
</apply>
</apply>
</math>
</component>
<component name="L_type_Ca_channel_f_12_gate">
<variable units="dimensionless" public_interface="out" name="f_12" initial_value="0.9999529"/>
<variable units="dimensionless" name="f_12_infinity"/>
<variable units="second" name="tau_f_12"/>
<variable units="millivolt" public_interface="in" name="V"/>
<variable units="second" public_interface="in" name="time"/>
<math xmlns="http://www.w3.org/1998/Math/MathML">
<apply>
<eq/>
<ci>f_12_infinity</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">26.7</cn>
</apply>
<cn cellml:units="millivolt">5.4</cn>
</apply>
</apply>
</apply>
</apply>
</apply>
<apply>
<eq/>
<ci>tau_f_12</ci>
<apply>
<plus/>
<apply>
<times/>
<cn cellml:units="second">0.041</cn>
<apply>
<exp/>
<apply>
<minus/>
<apply>
<power/>
<apply>
<divide/>
<apply>
<plus/>
<ci>V</ci>
<cn cellml:units="millivolt">47</cn>
</apply>
<cn cellml:units="millivolt">12</cn>
</apply>
<cn cellml:units="dimensionless">2</cn>
</apply>
</apply>
</apply>
</apply>
<apply>
<divide/>
<cn cellml:units="second">0.08</cn>
<apply>
<plus/>
<cn cellml:units="dimensionless">1</cn>
<apply>
<exp/>
<apply>
<divide/>
<apply>
<plus/>
<ci>V</ci>
<cn cellml:units="millivolt">55</cn>
</apply>
<apply>
<minus/>
<cn cellml:units="millivolt">5</cn>
</apply>
</apply>
</apply>
</apply>
</apply>
<apply>
<divide/>
<cn cellml:units="second">0.015</cn>
<apply>
<plus/>
<cn cellml:units="dimensionless">1</cn>
<apply>
<exp/>
<apply>
<divide/>
<apply>
<plus/>
<ci>V</ci>
<cn cellml:units="millivolt">75</cn>
</apply>
<cn cellml:units="millivolt">25</cn>
</apply>
</apply>
</apply>
</apply>
<cn cellml:units="second">0.0017</cn>
</apply>
</apply>
<apply>
<eq/>
<apply>
<diff/>
<bvar>
<ci>time</ci>
</bvar>
<ci>f_12</ci>
</apply>
<apply>
<divide/>
<apply>
<minus/>
<ci>f_12_infinity</ci>
<ci>f_12</ci>
</apply>
<ci>tau_f_12</ci>
</apply>
</apply>
</math>
</component>
<component name="L_type_Ca_channel_Ca_inact_gate">
<variable units="dimensionless" public_interface="out" name="Ca_inact" initial_value="0.9913102"/>
<variable units="second" name="tau_Ca_inact" initial_value="0.009"/>
<variable units="dimensionless" name="Ca_inact_infinity"/>
<variable units="millivolt" public_interface="in" name="V"/>
<variable units="second" public_interface="in" name="time"/>
<variable units="millimolar" public_interface="in" name="Ca_ss"/>
<math xmlns="http://www.w3.org/1998/Math/MathML">
<apply>
<eq/>
<ci>Ca_inact_infinity</ci>
<apply>
<divide/>
<cn cellml:units="dimensionless">1</cn>
<apply>
<plus/>
<cn cellml:units="dimensionless">1</cn>
<apply>
<divide/>
<ci>Ca_ss</ci>
<cn cellml:units="millimolar">0.01</cn>
</apply>
</apply>
</apply>
</apply>
<apply>
<eq/>
<apply>
<diff/>
<bvar>
<ci>time</ci>
</bvar>
<ci>Ca_inact</ci>
</apply>
<apply>
<divide/>
<apply>
<minus/>
<ci>Ca_inact_infinity</ci>
<ci>Ca_inact</ci>
</apply>
<ci>tau_Ca_inact</ci>
</apply>
</apply>
</math>
</component>
<component name="Ca_independent_transient_outward_K_current">
<variable units="nanoA" public_interface="out" cmeta:id="Ca_independent_transient_outward_K_current_i_t" name="i_t"/>
<variable units="millivolt" public_interface="out" name="E_K"/>
<variable units="microS" name="g_t" initial_value="0.035"/>
<variable units="dimensionless" name="a" initial_value="0.886"/>
<variable units="dimensionless" name="b" initial_value="0.114"/>
<variable units="second" public_interface="in" private_interface="out" name="time"/>
<variable units="millivolt" public_interface="in" private_interface="out" name="V"/>
<variable units="millijoule_per_mole_kelvin" public_interface="in" name="R"/>
<variable units="coulomb_per_mole" public_interface="in" name="F"/>
<variable units="kelvin" public_interface="in" name="T"/>
<variable units="millimolar" public_interface="in" name="K_o"/>
<variable units="millimolar" public_interface="in" name="K_i"/>
<variable units="dimensionless" private_interface="in" name="r"/>
<variable units="dimensionless" private_interface="in" name="s"/>
<variable units="dimensionless" private_interface="in" name="s_slow"/>
<math xmlns="http://www.w3.org/1998/Math/MathML">
<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>K_o</ci>
<ci>K_i</ci>
</apply>
</apply>
</apply>
</apply>
<apply>
<eq/>
<ci>i_t</ci>
<apply>
<times/>
<ci>g_t</ci>
<ci>r</ci>
<apply>
<plus/>
<apply>
<times/>
<ci>a</ci>
<ci>s</ci>
</apply>
<apply>
<times/>
<ci>b</ci>
<ci>s_slow</ci>
</apply>
</apply>
<apply>
<minus/>
<ci>V</ci>
<ci>E_K</ci>
</apply>
</apply>
</apply>
</math>
</component>
<component name="Ca_independent_transient_outward_K_current_r_gate">
<variable units="dimensionless" public_interface="out" name="r" initial_value="0.002191519"/>
<variable units="second" name="tau_r"/>
<variable units="dimensionless" name="r_infinity"/>
<variable units="millivolt" public_interface="in" name="V"/>
<variable units="second" public_interface="in" name="time"/>
<math xmlns="http://www.w3.org/1998/Math/MathML">
<apply>
<eq/>
<ci>r_infinity</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">10.6</cn>
</apply>
<apply>
<minus/>
<cn cellml:units="millivolt">11.42</cn>
</apply>
</apply>
</apply>
</apply>
</apply>
</apply>
<apply>
<eq/>
<ci>tau_r</ci>
<apply>
<divide/>
<cn cellml:units="second">1</cn>
<apply>
<plus/>
<apply>
<times/>
<cn cellml:units="dimensionless">45.16</cn>
<apply>
<exp/>
<apply>
<times/>
<cn cellml:units="per_millivolt">0.03577</cn>
<apply>
<plus/>
<ci>V</ci>
<cn cellml:units="millivolt">50</cn>
</apply>
</apply>
</apply>
</apply>
<apply>
<times/>
<cn cellml:units="dimensionless">98.9</cn>
<apply>
<exp/>
<apply>
<times/>
<apply>
<minus/>
<cn cellml:units="per_millivolt">0.1</cn>
</apply>
<apply>
<plus/>
<ci>V</ci>
<cn cellml:units="millivolt">38</cn>
</apply>
</apply>
</apply>
</apply>
</apply>
</apply>
</apply>
<apply>
<eq/>
<apply>
<diff/>
<bvar>
<ci>time</ci>
</bvar>
<ci>r</ci>
</apply>
<apply>
<divide/>
<apply>
<minus/>
<ci>r_infinity</ci>
<ci>r</ci>
</apply>
<ci>tau_r</ci>
</apply>
</apply>
</math>
</component>
<component name="Ca_independent_transient_outward_K_current_s_gate">
<variable units="dimensionless" public_interface="out" name="s" initial_value="0.9842542"/>
<variable units="second" name="tau_s"/>
<variable units="dimensionless" name="s_infinity"/>
<variable units="millivolt" public_interface="in" name="V"/>
<variable units="second" public_interface="in" name="time"/>
<math xmlns="http://www.w3.org/1998/Math/MathML">
<apply>
<eq/>
<ci>s_infinity</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">45.3</cn>
</apply>
<cn cellml:units="millivolt">6.8841</cn>
</apply>
</apply>
</apply>
</apply>
</apply>
<apply>
<eq/>
<ci>tau_s</ci>
<apply>
<plus/>
<apply>
<times/>
<cn cellml:units="second">0.35</cn>
<apply>
<exp/>
<apply>
<minus/>
<apply>
<power/>
<apply>
<divide/>
<apply>
<plus/>
<ci>V</ci>
<cn cellml:units="millivolt">70</cn>
</apply>
<cn cellml:units="millivolt">15</cn>
</apply>
<cn cellml:units="dimensionless">2</cn>
</apply>
</apply>
</apply>
</apply>
<cn cellml:units="second">0.035</cn>
</apply>
</apply>
<apply>
<eq/>
<apply>
<diff/>
<bvar>
<ci>time</ci>
</bvar>
<ci>s</ci>
</apply>
<apply>
<divide/>
<apply>
<minus/>
<ci>s_infinity</ci>
<ci>s</ci>
</apply>
<ci>tau_s</ci>
</apply>
</apply>
</math>
</component>
<component name="Ca_independent_transient_outward_K_current_s_slow_gate">
<variable units="dimensionless" public_interface="out" name="s_slow" initial_value="0.6421196"/>
<variable units="second" name="tau_s_slow"/>
<variable units="dimensionless" name="s_slow_infinity"/>
<variable units="millivolt" public_interface="in" name="V"/>
<variable units="second" public_interface="in" name="time"/>
<math xmlns="http://www.w3.org/1998/Math/MathML">
<apply>
<eq/>
<ci>s_slow_infinity</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">45.3</cn>
</apply>
<cn cellml:units="millivolt">6.8841</cn>
</apply>
</apply>
</apply>
</apply>
</apply>
<apply>
<eq/>
<ci>tau_s_slow</ci>
<apply>
<plus/>
<apply>
<times/>
<cn cellml:units="second">3.7</cn>
<apply>
<exp/>
<apply>
<minus/>
<apply>
<power/>
<apply>
<divide/>
<apply>
<plus/>
<ci>V</ci>
<cn cellml:units="millivolt">70</cn>
</apply>
<cn cellml:units="millivolt">30</cn>
</apply>
<cn cellml:units="dimensionless">2</cn>
</apply>
</apply>
</apply>
</apply>
<cn cellml:units="second">0.035</cn>
</apply>
</apply>
<apply>
<eq/>
<apply>
<diff/>
<bvar>
<ci>time</ci>
</bvar>
<ci>s_slow</ci>
</apply>
<apply>
<divide/>
<apply>
<minus/>
<ci>s_slow_infinity</ci>
<ci>s_slow</ci>
</apply>
<ci>tau_s_slow</ci>
</apply>
</apply>
</math>
</component>
<component name="steady_state_outward_K_current">
<variable units="nanoA" public_interface="out" cmeta:id="steady_state_outward_K_current_i_ss" name="i_ss"/>
<variable units="microS" name="g_ss" initial_value="0.007"/>
<variable units="second" public_interface="in" private_interface="out" name="time"/>
<variable units="millivolt" public_interface="in" private_interface="out" name="V"/>
<variable units="millivolt" public_interface="in" name="E_K"/>
<variable units="dimensionless" private_interface="in" name="r_ss"/>
<variable units="dimensionless" private_interface="in" name="s_ss"/>
<math xmlns="http://www.w3.org/1998/Math/MathML">
<apply>
<eq/>
<ci>i_ss</ci>
<apply>
<times/>
<ci>g_ss</ci>
<ci>r_ss</ci>
<ci>s_ss</ci>
<apply>
<minus/>
<ci>V</ci>
<ci>E_K</ci>
</apply>
</apply>
</apply>
</math>
</component>
<component name="steady_state_outward_K_current_r_ss_gate">
<variable units="dimensionless" public_interface="out" name="r_ss" initial_value="0.002907171"/>
<variable units="second" name="tau_r_ss"/>
<variable units="dimensionless" name="r_ss_infinity"/>
<variable units="millivolt" public_interface="in" name="V"/>
<variable units="second" public_interface="in" name="time"/>
<math xmlns="http://www.w3.org/1998/Math/MathML">
<apply>
<eq/>
<ci>r_ss_infinity</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">11.5</cn>
</apply>
<apply>
<minus/>
<cn cellml:units="millivolt">11.82</cn>
</apply>
</apply>
</apply>
</apply>
</apply>
</apply>
<apply>
<eq/>
<ci>tau_r_ss</ci>
<apply>
<divide/>
<cn cellml:units="second">10</cn>
<apply>
<plus/>
<apply>
<times/>
<cn cellml:units="dimensionless">45.16</cn>
<apply>
<exp/>
<apply>
<times/>
<cn cellml:units="per_millivolt">0.03577</cn>
<apply>
<plus/>
<ci>V</ci>
<cn cellml:units="millivolt">50</cn>
</apply>
</apply>
</apply>
</apply>
<apply>
<times/>
<cn cellml:units="dimensionless">98.9</cn>
<apply>
<exp/>
<apply>
<times/>
<apply>
<minus/>
<cn cellml:units="per_millivolt">0.1</cn>
</apply>
<apply>
<plus/>
<ci>V</ci>
<cn cellml:units="millivolt">38</cn>
</apply>
</apply>
</apply>
</apply>
</apply>
</apply>
</apply>
<apply>
<eq/>
<apply>
<diff/>
<bvar>
<ci>time</ci>
</bvar>
<ci>r_ss</ci>
</apply>
<apply>
<divide/>
<apply>
<minus/>
<ci>r_ss_infinity</ci>
<ci>r_ss</ci>
</apply>
<ci>tau_r_ss</ci>
</apply>
</apply>
</math>
</component>
<component name="steady_state_outward_K_current_s_ss_gate">
<variable units="dimensionless" public_interface="out" name="s_ss" initial_value="0.3142767"/>
<variable units="second" name="tau_s_ss"/>
<variable units="dimensionless" name="s_ss_infinity"/>
<variable units="millivolt" public_interface="in" name="V"/>
<variable units="second" public_interface="in" name="time"/>
<math xmlns="http://www.w3.org/1998/Math/MathML">
<apply>
<eq/>
<ci>s_ss_infinity</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">87.5</cn>
</apply>
<cn cellml:units="millivolt">10.3</cn>
</apply>
</apply>
</apply>
</apply>
</apply>
<apply>
<eq/>
<ci>tau_s_ss</ci>
<cn cellml:units="second">2.1</cn>
</apply>
<apply>
<eq/>
<apply>
<diff/>
<bvar>
<ci>time</ci>
</bvar>
<ci>s_ss</ci>
</apply>
<apply>
<divide/>
<apply>
<minus/>
<ci>s_ss_infinity</ci>
<ci>s_ss</ci>
</apply>
<ci>tau_s_ss</ci>
</apply>
</apply>
</math>
</component>
<component name="inward_rectifier">
<variable units="nanoA" public_interface="out" cmeta:id="inward_rectifier_i_K1" name="i_K1"/>
<variable units="microS" name="g_K1" initial_value="0.024"/>
<variable units="second" public_interface="in" name="time"/>
<variable units="millivolt" public_interface="in" name="V"/>
<variable units="millijoule_per_mole_kelvin" public_interface="in" name="R"/>
<variable units="coulomb_per_mole" public_interface="in" name="F"/>
<variable units="kelvin" public_interface="in" name="T"/>
<variable units="millimolar" public_interface="in" name="K_o"/>
<variable units="millimolar" public_interface="in" name="K_i"/>
<variable units="millivolt" public_interface="in" name="E_K"/>
<math xmlns="http://www.w3.org/1998/Math/MathML">
<apply>
<eq/>
<ci>i_K1</ci>
<apply>
<plus/>
<apply>
<divide/>
<apply>
<times/>
<apply>
<plus/>
<apply>
<divide/>
<cn cellml:units="nanoA">48</cn>
<apply>
<plus/>
<apply>
<exp/>
<apply>
<divide/>
<apply>
<plus/>
<ci>V</ci>
<cn cellml:units="millivolt">37</cn>
</apply>
<cn cellml:units="millivolt">25</cn>
</apply>
</apply>
<apply>
<exp/>
<apply>
<divide/>
<apply>
<plus/>
<ci>V</ci>
<cn cellml:units="millivolt">37</cn>
</apply>
<apply>
<minus/>
<cn cellml:units="millivolt">25</cn>
</apply>
</apply>
</apply>
</apply>
</apply>
<cn cellml:units="nanoA">10</cn>
</apply>
<cn cellml:units="dimensionless">0.001</cn>
</apply>
<apply>
<plus/>
<cn cellml:units="dimensionless">1</cn>
<apply>
<exp/>
<apply>
<divide/>
<apply>
<minus/>
<ci>V</ci>
<apply>
<plus/>
<ci>E_K</ci>
<cn cellml:units="millivolt">76.77</cn>
</apply>
</apply>
<apply>
<minus/>
<cn cellml:units="millivolt">17</cn>
</apply>
</apply>
</apply>
</apply>
</apply>
<apply>
<divide/>
<apply>
<times/>
<ci>g_K1</ci>
<apply>
<minus/>
<ci>V</ci>
<apply>
<plus/>
<ci>E_K</ci>
<cn cellml:units="millivolt">1.73</cn>
</apply>
</apply>
</apply>
<apply>
<times/>
<apply>
<plus/>
<cn cellml:units="dimensionless">1</cn>
<apply>
<exp/>
<apply>
<divide/>
<apply>
<times/>
<cn cellml:units="dimensionless">1.613</cn>
<ci>F</ci>
<apply>
<minus/>
<ci>V</ci>
<apply>
<plus/>
<ci>E_K</ci>
<cn cellml:units="millivolt">1.73</cn>
</apply>
</apply>
</apply>
<apply>
<times/>
<ci>R</ci>
<ci>T</ci>
</apply>
</apply>
</apply>
</apply>
<apply>
<plus/>
<cn cellml:units="dimensionless">1</cn>
<apply>
<exp/>
<apply>
<divide/>
<apply>
<minus/>
<ci>K_o</ci>
<cn cellml:units="millimolar">0.9988</cn>
</apply>
<apply>
<minus/>
<cn cellml:units="millimolar">0.124</cn>
</apply>
</apply>
</apply>
</apply>
</apply>
</apply>
</apply>
</apply>
</math>
</component>
<component name="hyperpolarisation_activated_current">
<variable units="nanoA" public_interface="out" cmeta:id="hyperpolarisation_activated_current_i_f" name="i_f"/>
<variable units="nanoA" public_interface="out" name="i_f_Na"/>
<variable units="nanoA" public_interface="out" name="i_f_K"/>
<variable units="microS" name="g_f" initial_value="0.00145"/>
<variable units="dimensionless" name="f_Na" initial_value="0.2"/>
<variable units="dimensionless" name="f_K"/>
<variable units="second" public_interface="in" private_interface="out" name="time"/>
<variable units="millivolt" public_interface="in" private_interface="out" name="V"/>
<variable units="millivolt" public_interface="in" name="E_K"/>
<variable units="millivolt" public_interface="in" name="E_Na"/>
<variable units="dimensionless" private_interface="in" name="y"/>
<math xmlns="http://www.w3.org/1998/Math/MathML">
<apply>
<eq/>
<ci>f_K</ci>
<apply>
<minus/>
<cn cellml:units="dimensionless">1</cn>
<ci>f_Na</ci>
</apply>
</apply>
<apply>
<eq/>
<ci>i_f_Na</ci>
<apply>
<times/>
<ci>g_f</ci>
<ci>y</ci>
<ci>f_Na</ci>
<apply>
<minus/>
<ci>V</ci>
<ci>E_Na</ci>
</apply>
</apply>
</apply>
<apply>
<eq/>
<ci>i_f_K</ci>
<apply>
<times/>
<ci>g_f</ci>
<ci>y</ci>
<ci>f_K</ci>
<apply>
<minus/>
<ci>V</ci>
<ci>E_K</ci>
</apply>
</apply>
</apply>
<apply>
<eq/>
<ci>i_f</ci>
<apply>
<plus/>
<ci>i_f_Na</ci>
<ci>i_f_K</ci>
</apply>
</apply>
</math>
</component>
<component name="hyperpolarisation_activated_current_y_gate">
<variable units="dimensionless" public_interface="out" name="y" initial_value="0.003578708"/>
<variable units="second" name="tau_y"/>
<variable units="dimensionless" name="y_infinity"/>
<variable units="millivolt" public_interface="in" name="V"/>
<variable units="second" public_interface="in" name="time"/>
<math xmlns="http://www.w3.org/1998/Math/MathML">
<apply>
<eq/>
<ci>y_infinity</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">138.6</cn>
</apply>
<cn cellml:units="millivolt">10.48</cn>
</apply>
</apply>
</apply>
</apply>
</apply>
<apply>
<eq/>
<ci>tau_y</ci>
<apply>
<divide/>
<cn cellml:units="second">1</cn>
<apply>
<plus/>
<apply>
<times/>
<cn cellml:units="dimensionless">0.11885</cn>
<apply>
<exp/>
<apply>
<divide/>
<apply>
<plus/>
<ci>V</ci>
<cn cellml:units="millivolt">80</cn>
</apply>
<cn cellml:units="millivolt">28.37</cn>
</apply>
</apply>
</apply>
<apply>
<times/>
<cn cellml:units="dimensionless">0.5623</cn>
<apply>
<exp/>
<apply>
<divide/>
<apply>
<plus/>
<ci>V</ci>
<cn cellml:units="millivolt">80</cn>
</apply>
<apply>
<minus/>
<cn cellml:units="millivolt">14.19</cn>
</apply>
</apply>
</apply>
</apply>
</apply>
</apply>
</apply>
<apply>
<eq/>
<apply>
<diff/>
<bvar>
<ci>time</ci>
</bvar>
<ci>y</ci>
</apply>
<apply>
<divide/>
<apply>
<minus/>
<ci>y_infinity</ci>
<ci>y</ci>
</apply>
<ci>tau_y</ci>
</apply>
</apply>
</math>
</component>
<component name="background_currents">
<variable units="nanoA" public_interface="out" cmeta:id="background_currents_i_B" name="i_B"/>
<variable units="nanoA" public_interface="out" name="i_B_Na"/>
<variable units="nanoA" public_interface="out" name="i_B_Ca"/>
<variable units="nanoA" public_interface="out" name="i_B_K"/>
<variable units="microS" name="g_B_Na" initial_value="0.00008015"/>
<variable units="microS" name="g_B_Ca" initial_value="0.0000324"/>
<variable units="microS" name="g_B_K" initial_value="0.000138"/>
<variable units="millivolt" name="E_Ca"/>
<variable units="millivolt" public_interface="in" name="E_Na"/>
<variable units="millivolt" public_interface="in" name="E_K"/>
<variable units="millimolar" public_interface="in" name="Ca_o"/>
<variable units="millimolar" public_interface="in" name="Ca_i"/>
<variable units="millijoule_per_mole_kelvin" public_interface="in" name="R"/>
<variable units="kelvin" public_interface="in" name="T"/>
<variable units="coulomb_per_mole" public_interface="in" name="F"/>
<variable units="second" public_interface="in" name="time"/>
<variable units="millivolt" public_interface="in" name="V"/>
<math xmlns="http://www.w3.org/1998/Math/MathML">
<apply>
<eq/>
<ci>E_Ca</ci>
<apply>
<times/>
<apply>
<divide/>
<apply>
<times/>
<cn cellml:units="dimensionless">0.5</cn>
<ci>R</ci>
<ci>T</ci>
</apply>
<ci>F</ci>
</apply>
<apply>
<ln/>
<apply>
<divide/>
<ci>Ca_o</ci>
<ci>Ca_i</ci>
</apply>
</apply>
</apply>
</apply>
<apply>
<eq/>
<ci>i_B_Na</ci>
<apply>
<times/>
<ci>g_B_Na</ci>
<apply>
<minus/>
<ci>V</ci>
<ci>E_Na</ci>
</apply>
</apply>
</apply>
<apply>
<eq/>
<ci>i_B_Ca</ci>
<apply>
<times/>
<ci>g_B_Ca</ci>
<apply>
<minus/>
<ci>V</ci>
<ci>E_Ca</ci>
</apply>
</apply>
</apply>
<apply>
<eq/>
<ci>i_B_K</ci>
<apply>
<times/>
<ci>g_B_K</ci>
<apply>
<minus/>
<ci>V</ci>
<ci>E_K</ci>
</apply>
</apply>
</apply>
<apply>
<eq/>
<ci>i_B</ci>
<apply>
<plus/>
<ci>i_B_Na</ci>
<ci>i_B_Ca</ci>
<ci>i_B_K</ci>
</apply>
</apply>
</math>
</component>
<component name="sodium_potassium_pump">
<variable units="nanoA" public_interface="out" cmeta:id="sodium_potassium_pump_i_NaK" name="i_NaK"/>
<variable units="nanoA" name="i_NaK_max" initial_value="0.08"/>
<variable units="millimolar" name="K_m_K" initial_value="1.5"/>
<variable units="millimolar" name="K_m_Na" initial_value="10"/>
<variable units="dimensionless" name="sigma"/>
<variable units="millimolar" public_interface="in" name="K_o"/>
<variable units="millimolar" public_interface="in" name="Na_o"/>
<variable units="millimolar" public_interface="in" name="Na_i"/>
<variable units="millijoule_per_mole_kelvin" public_interface="in" name="R"/>
<variable units="coulomb_per_mole" public_interface="in" name="F"/>
<variable units="kelvin" public_interface="in" name="T"/>
<variable units="millivolt" public_interface="in" name="V"/>
<variable units="second" public_interface="in" name="time"/>
<math xmlns="http://www.w3.org/1998/Math/MathML">
<apply>
<eq/>
<ci>sigma</ci>
<apply>
<divide/>
<apply>
<minus/>
<apply>
<exp/>
<apply>
<divide/>
<ci>Na_o</ci>
<cn cellml:units="millimolar">67.3</cn>
</apply>
</apply>
<cn cellml:units="dimensionless">1</cn>
</apply>
<cn cellml:units="dimensionless">7</cn>
</apply>
</apply>
<apply>
<eq/>
<ci>i_NaK</ci>
<apply>
<divide/>
<apply>
<times/>
<apply>
<divide/>
<apply>
<times/>
<apply>
<divide/>
<apply>
<times/>
<ci>i_NaK_max</ci>
<cn cellml:units="dimensionless">1</cn>
</apply>
<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>
<ci>K_o</ci>
</apply>
<apply>
<plus/>
<ci>K_o</ci>
<ci>K_m_K</ci>
</apply>
</apply>
<cn cellml:units="dimensionless">1</cn>
</apply>
<apply>
<plus/>
<cn cellml:units="dimensionless">1</cn>
<apply>
<power/>
<apply>
<divide/>
<ci>K_m_Na</ci>
<ci>Na_i</ci>
</apply>
<cn cellml:units="dimensionless">1.5</cn>
</apply>
</apply>
</apply>
</apply>
</math>
</component>
<component name="sarcolemmal_calcium_pump_current">
<variable units="nanoA" public_interface="out" cmeta:id="sarcolemmal_calcium_pump_current_i_Ca_P" name="i_Ca_P"/>
<variable units="nanoA" name="i_Ca_P_max" initial_value="0.004"/>
<variable units="millimolar" public_interface="in" name="Ca_i"/>
<variable units="second" public_interface="in" name="time"/>
<math xmlns="http://www.w3.org/1998/Math/MathML">
<apply>
<eq/>
<ci>i_Ca_P</ci>
<apply>
<divide/>
<apply>
<times/>
<ci>i_Ca_P_max</ci>
<ci>Ca_i</ci>
</apply>
<apply>
<plus/>
<ci>Ca_i</ci>
<cn cellml:units="millimolar">0.0004</cn>
</apply>
</apply>
</apply>
</math>
</component>
<component name="Na_Ca_ion_exchanger_current">
<variable units="nanoA" public_interface="out" cmeta:id="Na_Ca_ion_exchanger_current_i_NaCa" name="i_NaCa"/>
<variable units="nanoA_millimolar_4" name="K_NaCa" initial_value="0.000009984"/>
<variable units="millimolar_4" name="d_NaCa" initial_value="0.0001"/>
<variable units="dimensionless" name="gamma_NaCa" initial_value="0.5"/>
<variable units="millimolar" public_interface="in" name="Na_i"/>
<variable units="millimolar" public_interface="in" name="Na_o"/>
<variable units="millimolar" public_interface="in" name="Ca_i"/>
<variable units="millimolar" public_interface="in" name="Ca_o"/>
<variable units="millivolt" public_interface="in" name="V"/>
<variable units="second" public_interface="in" name="time"/>
<math xmlns="http://www.w3.org/1998/Math/MathML">
<apply>
<eq/>
<ci>i_NaCa</ci>
<apply>
<divide/>
<apply>
<times/>
<ci>K_NaCa</ci>
<apply>
<minus/>
<apply>
<times/>
<apply>
<power/>
<ci>Na_i</ci>
<cn cellml:units="dimensionless">3</cn>
</apply>
<ci>Ca_o</ci>
<apply>
<exp/>
<apply>
<times/>
<cn cellml:units="per_millivolt">0.03743</cn>
<ci>V</ci>
<ci>gamma_NaCa</ci>
</apply>
</apply>
</apply>
<apply>
<times/>
<apply>
<power/>
<ci>Na_o</ci>
<cn cellml:units="dimensionless">3</cn>
</apply>
<ci>Ca_i</ci>
<apply>
<exp/>
<apply>
<times/>
<cn cellml:units="per_millivolt">0.03743</cn>
<ci>V</ci>
<apply>
<minus/>
<ci>gamma_NaCa</ci>
<cn cellml:units="dimensionless">1</cn>
</apply>
</apply>
</apply>
</apply>
</apply>
</apply>
<apply>
<plus/>
<cn cellml:units="dimensionless">1</cn>
<apply>
<times/>
<ci>d_NaCa</ci>
<apply>
<plus/>
<apply>
<times/>
<ci>Ca_i</ci>
<apply>
<power/>
<ci>Na_o</ci>
<cn cellml:units="dimensionless">3</cn>
</apply>
</apply>
<apply>
<times/>
<ci>Ca_o</ci>
<apply>
<power/>
<ci>Na_i</ci>
<cn cellml:units="dimensionless">3</cn>
</apply>
</apply>
</apply>
</apply>
</apply>
</apply>
</apply>
</math>
</component>
<component name="SR_Ca_release_channel">
<variable units="millimolar_per_second" public_interface="out" cmeta:id="SR_Ca_release_channel_J_rel" name="J_rel"/>
<variable units="per_second" name="v1" initial_value="1.8e3"/>
<variable units="per_second" name="k_a_plus" initial_value="12.15e12"/>
<variable units="per_second" name="k_a_minus" initial_value="576"/>
<variable units="per_second" name="k_b_plus" initial_value="4.05e9"/>
<variable units="per_second" name="k_b_minus" initial_value="1930"/>
<variable units="per_second" name="k_c_plus" initial_value="100"/>
<variable units="per_second" name="k_c_minus" initial_value="0.8"/>
<variable units="dimensionless" name="P_O1" initial_value="0.0004327548"/>
<variable units="dimensionless" name="P_O2" initial_value="0.000000000606254"/>
<variable units="dimensionless" name="P_C1" initial_value="0.6348229"/>
<variable units="dimensionless" name="P_C2" initial_value="0.3647471"/>
<variable units="dimensionless" name="n" initial_value="4"/>
<variable units="dimensionless" name="m" initial_value="3"/>
<variable units="second" public_interface="in" name="time"/>
<variable units="millimolar" public_interface="in" name="Ca_ss"/>
<variable units="millimolar" public_interface="in" name="Ca_JSR"/>
<math xmlns="http://www.w3.org/1998/Math/MathML">
<apply>
<eq/>
<apply>
<diff/>
<bvar>
<ci>time</ci>
</bvar>
<ci>P_C1</ci>
</apply>
<apply>
<plus/>
<apply>
<times/>
<apply>
<minus/>
<ci>k_a_plus</ci>
</apply>
<apply>
<power/>
<apply>
<divide/>
<ci>Ca_ss</ci>
<cn cellml:units="millimolar">1</cn>
</apply>
<ci>n</ci>
</apply>
<ci>P_C1</ci>
</apply>
<apply>
<times/>
<ci>k_a_minus</ci>
<ci>P_O1</ci>
</apply>
</apply>
</apply>
<apply>
<eq/>
<apply>
<diff/>
<bvar>
<ci>time</ci>
</bvar>
<ci>P_O1</ci>
</apply>
<apply>
<plus/>
<apply>
<minus/>
<apply>
<times/>
<ci>k_a_plus</ci>
<apply>
<power/>
<apply>
<divide/>
<ci>Ca_ss</ci>
<cn cellml:units="millimolar">1</cn>
</apply>
<ci>n</ci>
</apply>
<ci>P_C1</ci>
</apply>
<apply>
<plus/>
<apply>
<times/>
<ci>k_a_minus</ci>
<ci>P_O1</ci>
</apply>
<apply>
<times/>
<ci>k_b_plus</ci>
<apply>
<power/>
<apply>
<divide/>
<ci>Ca_ss</ci>
<cn cellml:units="millimolar">1</cn>
</apply>
<ci>m</ci>
</apply>
<ci>P_O1</ci>
</apply>
<apply>
<times/>
<ci>k_c_plus</ci>
<ci>P_O1</ci>
</apply>
</apply>
</apply>
<apply>
<times/>
<ci>k_b_minus</ci>
<ci>P_O2</ci>
</apply>
<apply>
<times/>
<ci>k_c_minus</ci>
<ci>P_C2</ci>
</apply>
</apply>
</apply>
<apply>
<eq/>
<apply>
<diff/>
<bvar>
<ci>time</ci>
</bvar>
<ci>P_O2</ci>
</apply>
<apply>
<minus/>
<apply>
<times/>
<ci>k_b_plus</ci>
<apply>
<power/>
<apply>
<divide/>
<ci>Ca_ss</ci>
<cn cellml:units="millimolar">1</cn>
</apply>
<ci>m</ci>
</apply>
<ci>P_O1</ci>
</apply>
<apply>
<times/>
<ci>k_b_minus</ci>
<ci>P_O2</ci>
</apply>
</apply>
</apply>
<apply>
<eq/>
<apply>
<diff/>
<bvar>
<ci>time</ci>
</bvar>
<ci>P_C2</ci>
</apply>
<apply>
<minus/>
<apply>
<times/>
<ci>k_c_plus</ci>
<ci>P_O1</ci>
</apply>
<apply>
<times/>
<ci>k_c_minus</ci>
<ci>P_C2</ci>
</apply>
</apply>
</apply>
<apply>
<eq/>
<ci>J_rel</ci>
<apply>
<times/>
<ci>v1</ci>
<apply>
<plus/>
<ci>P_O1</ci>
<ci>P_O2</ci>
</apply>
<apply>
<minus/>
<ci>Ca_JSR</ci>
<ci>Ca_ss</ci>
</apply>
</apply>
</apply>
</math>
</component>
<component name="SERCA2a_pump">
<variable units="millimolar_per_second" public_interface="out" cmeta:id="SERCA2a_pump_J_up" name="J_up"/>
<variable units="millimolar" name="K_fb" initial_value="0.000168"/>
<variable units="millimolar" name="K_rb" initial_value="3.29"/>
<variable units="dimensionless" name="fb"/>
<variable units="dimensionless" name="rb"/>
<variable units="millimolar_per_second" name="Vmaxf" initial_value="0.04"/>
<variable units="millimolar_per_second" name="Vmaxr" initial_value="0.9"/>
<variable units="dimensionless" name="K_SR" initial_value="1"/>
<variable units="dimensionless" name="N_fb" initial_value="1.2"/>
<variable units="dimensionless" name="N_rb" initial_value="1"/>
<variable units="second" public_interface="in" name="time"/>
<variable units="millimolar" public_interface="in" name="Ca_i"/>
<variable units="millimolar" public_interface="in" name="Ca_NSR"/>
<math xmlns="http://www.w3.org/1998/Math/MathML">
<apply>
<eq/>
<ci>fb</ci>
<apply>
<power/>
<apply>
<divide/>
<ci>Ca_i</ci>
<ci>K_fb</ci>
</apply>
<ci>N_fb</ci>
</apply>
</apply>
<apply>
<eq/>
<ci>rb</ci>
<apply>
<power/>
<apply>
<divide/>
<ci>Ca_NSR</ci>
<ci>K_rb</ci>
</apply>
<ci>N_rb</ci>
</apply>
</apply>
<apply>
<eq/>
<ci>J_up</ci>
<apply>
<divide/>
<apply>
<times/>
<ci>K_SR</ci>
<apply>
<minus/>
<apply>
<times/>
<ci>Vmaxf</ci>
<ci>fb</ci>
</apply>
<apply>
<times/>
<ci>Vmaxr</ci>
<ci>rb</ci>
</apply>
</apply>
</apply>
<apply>
<plus/>
<cn cellml:units="dimensionless">1</cn>
<ci>fb</ci>
<ci>rb</ci>
</apply>
</apply>
</apply>
</math>
</component>
<component name="intracellular_and_SR_Ca_fluxes">
<variable units="millimolar_per_second" public_interface="out" name="J_tr"/>
<variable units="millimolar_per_second" public_interface="out" cmeta:id="intracellular_and_SR_Ca_fluxes_J_xfer" name="J_xfer"/>
<variable units="millimolar_per_second" public_interface="out" name="J_trpn"/>
<variable units="second" name="tau_tr" initial_value="0.0005747"/>
<variable units="second" name="tau_xfer" initial_value="0.0267"/>
<variable units="millimolar" name="HTRPNCa" initial_value="1.394301e-1"/>
<variable units="millimolar" name="LTRPNCa" initial_value="5.1619e-3"/>
<variable units="millimolar_per_second" name="J_HTRPNCa"/>
<variable units="millimolar_per_second" name="J_LTRPNCa"/>
<variable units="millimolar" name="HTRPN_tot" initial_value="0.14"/>
<variable units="millimolar" name="LTRPN_tot" initial_value="0.07"/>
<variable units="per_millimolar_per_second" name="k_htrpn_plus" initial_value="200000"/>
<variable units="per_second" name="k_htrpn_minus" initial_value="0.066"/>
<variable units="per_millimolar_per_second" name="k_ltrpn_plus" initial_value="40000"/>
<variable units="per_second" name="k_ltrpn_minus" initial_value="40"/>
<variable units="second" public_interface="in" name="time"/>
<variable units="millimolar" public_interface="in" name="Ca_ss"/>
<variable units="millimolar" public_interface="in" name="Ca_i"/>
<variable units="millimolar" public_interface="in" name="Ca_NSR"/>
<variable units="millimolar" public_interface="in" name="Ca_JSR"/>
<math xmlns="http://www.w3.org/1998/Math/MathML">
<apply>
<eq/>
<ci>J_tr</ci>
<apply>
<divide/>
<apply>
<minus/>
<ci>Ca_NSR</ci>
<ci>Ca_JSR</ci>
</apply>
<ci>tau_tr</ci>
</apply>
</apply>
<apply>
<eq/>
<ci>J_xfer</ci>
<apply>
<divide/>
<apply>
<minus/>
<ci>Ca_ss</ci>
<ci>Ca_i</ci>
</apply>
<ci>tau_xfer</ci>
</apply>
</apply>
<apply>
<eq/>
<ci>J_HTRPNCa</ci>
<apply>
<minus/>
<apply>
<times/>
<ci>k_htrpn_plus</ci>
<ci>Ca_i</ci>
<apply>
<minus/>
<ci>HTRPN_tot</ci>
<ci>HTRPNCa</ci>
</apply>
</apply>
<apply>
<times/>
<ci>k_htrpn_minus</ci>
<ci>HTRPNCa</ci>
</apply>
</apply>
</apply>
<apply>
<eq/>
<ci>J_LTRPNCa</ci>
<apply>
<minus/>
<apply>
<times/>
<ci>k_ltrpn_plus</ci>
<ci>Ca_i</ci>
<apply>
<minus/>
<ci>LTRPN_tot</ci>
<ci>LTRPNCa</ci>
</apply>
</apply>
<apply>
<times/>
<ci>k_ltrpn_minus</ci>
<ci>LTRPNCa</ci>
</apply>
</apply>
</apply>
<apply>
<eq/>
<ci>J_trpn</ci>
<apply>
<plus/>
<ci>J_HTRPNCa</ci>
<ci>J_LTRPNCa</ci>
</apply>
</apply>
</math>
</component>
<component name="intracellular_ion_concentrations">
<variable units="millimolar" public_interface="out" name="Na_i" initial_value="10.73519"/>
<variable units="millimolar" public_interface="out" name="Ca_i" initial_value="0.00007901351"/>
<variable units="millimolar" public_interface="out" name="K_i" initial_value="139.2751"/>
<variable units="millimolar" public_interface="out" name="Ca_ss" initial_value="0.00008737212"/>
<variable units="millimolar" public_interface="out" name="Ca_JSR" initial_value="0.06607948"/>
<variable units="millimolar" public_interface="out" name="Ca_NSR" initial_value="0.06600742"/>
<variable units="micro_litre" name="V_myo" initial_value="0.00000936"/>
<variable units="micro_litre" name="V_JSR" initial_value="0.00000056"/>
<variable units="micro_litre" name="V_NSR" initial_value="0.00000504"/>
<variable units="micro_litre" name="V_SS" initial_value="0.000000012"/>
<variable units="millimolar" name="K_mCMDN" initial_value="0.00238"/>
<variable units="millimolar" name="K_mCSQN" initial_value="0.8"/>
<variable units="millimolar" name="K_mEGTA" initial_value="0.00015"/>
<variable units="millimolar" name="CMDN_tot" initial_value="0.05"/>
<variable units="millimolar" name="CSQN_tot" initial_value="15"/>
<variable units="millimolar" name="EGTA_tot" initial_value="10"/>
<variable units="dimensionless" name="beta_i"/>
<variable units="dimensionless" name="beta_SS"/>
<variable units="dimensionless" name="beta_JSR"/>
<variable units="second" public_interface="in" name="time"/>
<variable units="coulomb_per_mole" public_interface="in" name="F"/>
<variable units="nanoA" public_interface="in" name="i_Na"/>
<variable units="nanoA" public_interface="in" name="i_Ca_L"/>
<variable units="nanoA" public_interface="in" name="i_B_Na"/>
<variable units="nanoA" public_interface="in" name="i_NaCa"/>
<variable units="nanoA" public_interface="in" name="i_NaK"/>
<variable units="nanoA" public_interface="in" name="i_f_Na"/>
<variable units="nanoA" public_interface="in" name="i_f_K"/>
<variable units="nanoA" public_interface="in" name="i_B_K"/>
<variable units="nanoA" public_interface="in" name="i_K1"/>
<variable units="nanoA" public_interface="in" name="i_t"/>
<variable units="nanoA" public_interface="in" name="i_ss"/>
<variable units="nanoA" public_interface="in" name="i_Ca_P"/>
<variable units="nanoA" public_interface="in" name="i_B_Ca"/>
<variable units="millimolar_per_second" public_interface="in" name="J_up"/>
<variable units="millimolar_per_second" public_interface="in" name="J_rel"/>
<variable units="millimolar_per_second" public_interface="in" name="J_xfer"/>
<variable units="millimolar_per_second" public_interface="in" name="J_trpn"/>
<variable units="millimolar_per_second" public_interface="in" name="J_tr"/>
<math xmlns="http://www.w3.org/1998/Math/MathML">
<apply>
<eq/>
<ci>beta_i</ci>
<apply>
<divide/>
<cn cellml:units="dimensionless">1</cn>
<apply>
<plus/>
<cn cellml:units="dimensionless">1</cn>
<apply>
<divide/>
<apply>
<times/>
<ci>CMDN_tot</ci>
<ci>K_mCMDN</ci>
</apply>
<apply>
<power/>
<apply>
<plus/>
<ci>K_mCMDN</ci>
<ci>Ca_i</ci>
</apply>
<cn cellml:units="dimensionless">2</cn>
</apply>
</apply>
<apply>
<divide/>
<apply>
<times/>
<ci>EGTA_tot</ci>
<ci>K_mEGTA</ci>
</apply>
<apply>
<power/>
<apply>
<plus/>
<ci>K_mEGTA</ci>
<ci>Ca_i</ci>
</apply>
<cn cellml:units="dimensionless">2</cn>
</apply>
</apply>
</apply>
</apply>
</apply>
<apply>
<eq/>
<ci>beta_SS</ci>
<apply>
<divide/>
<cn cellml:units="dimensionless">1</cn>
<apply>
<plus/>
<cn cellml:units="dimensionless">1</cn>
<apply>
<divide/>
<apply>
<times/>
<ci>CMDN_tot</ci>
<ci>K_mCMDN</ci>
</apply>
<apply>
<power/>
<apply>
<plus/>
<ci>K_mCMDN</ci>
<ci>Ca_ss</ci>
</apply>
<cn cellml:units="dimensionless">2</cn>
</apply>
</apply>
</apply>
</apply>
</apply>
<apply>
<eq/>
<ci>beta_JSR</ci>
<apply>
<divide/>
<cn cellml:units="dimensionless">1</cn>
<apply>
<plus/>
<cn cellml:units="dimensionless">1</cn>
<apply>
<divide/>
<apply>
<times/>
<ci>CSQN_tot</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>
<apply>
<eq/>
<apply>
<diff/>
<bvar>
<ci>time</ci>
</bvar>
<ci>Ca_i</ci>
</apply>
<apply>
<times/>
<ci>beta_i</ci>
<apply>
<minus/>
<ci>J_xfer</ci>
<apply>
<plus/>
<ci>J_up</ci>
<ci>J_trpn</ci>
<apply>
<divide/>
<apply>
<times/>
<apply>
<plus/>
<apply>
<minus/>
<ci>i_B_Ca</ci>
<apply>
<times/>
<cn cellml:units="dimensionless">2</cn>
<ci>i_NaCa</ci>
</apply>
</apply>
<ci>i_Ca_P</ci>
</apply>
<cn cellml:units="dimensionless">1</cn>
</apply>
<apply>
<times/>
<cn cellml:units="dimensionless">2</cn>
<ci>V_myo</ci>
<ci>F</ci>
</apply>
</apply>
</apply>
</apply>
</apply>
</apply>
<apply>
<eq/>
<apply>
<diff/>
<bvar>
<ci>time</ci>
</bvar>
<ci>Na_i</ci>
</apply>
<apply>
<divide/>
<apply>
<times/>
<apply>
<minus/>
<apply>
<plus/>
<ci>i_Na</ci>
<ci>i_B_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>
<ci>i_f_Na</ci>
</apply>
</apply>
<cn cellml:units="dimensionless">1</cn>
</apply>
<apply>
<times/>
<ci>V_myo</ci>
<ci>F</ci>
</apply>
</apply>
</apply>
<apply>
<eq/>
<apply>
<diff/>
<bvar>
<ci>time</ci>
</bvar>
<ci>K_i</ci>
</apply>
<apply>
<divide/>
<apply>
<times/>
<apply>
<minus/>
<apply>
<plus/>
<ci>i_ss</ci>
<ci>i_B_K</ci>
<ci>i_t</ci>
<ci>i_K1</ci>
<ci>i_f_K</ci>
<apply>
<times/>
<ci>i_NaK</ci>
<apply>
<minus/>
<cn cellml:units="dimensionless">2</cn>
</apply>
</apply>
</apply>
</apply>
<cn cellml:units="dimensionless">1</cn>
</apply>
<apply>
<times/>
<ci>V_myo</ci>
<ci>F</ci>
</apply>
</apply>
</apply>
<apply>
<eq/>
<apply>
<diff/>
<bvar>
<ci>time</ci>
</bvar>
<ci>Ca_ss</ci>
</apply>
<apply>
<times/>
<ci>beta_SS</ci>
<apply>
<minus/>
<apply>
<minus/>
<apply>
<divide/>
<apply>
<times/>
<ci>J_rel</ci>
<ci>V_JSR</ci>
</apply>
<ci>V_SS</ci>
</apply>
<apply>
<divide/>
<apply>
<times/>
<ci>J_xfer</ci>
<ci>V_myo</ci>
</apply>
<ci>V_SS</ci>
</apply>
</apply>
<apply>
<divide/>
<apply>
<times/>
<ci>i_Ca_L</ci>
<cn cellml:units="dimensionless">1</cn>
</apply>
<apply>
<times/>
<cn cellml:units="dimensionless">2</cn>
<ci>V_SS</ci>
<ci>F</ci>
</apply>
</apply>
</apply>
</apply>
</apply>
<apply>
<eq/>
<apply>
<diff/>
<bvar>
<ci>time</ci>
</bvar>
<ci>Ca_JSR</ci>
</apply>
<apply>
<times/>
<ci>beta_JSR</ci>
<apply>
<minus/>
<ci>J_tr</ci>
<ci>J_rel</ci>
</apply>
</apply>
</apply>
<apply>
<eq/>
<apply>
<diff/>
<bvar>
<ci>time</ci>
</bvar>
<ci>Ca_NSR</ci>
</apply>
<apply>
<minus/>
<apply>
<divide/>
<apply>
<times/>
<ci>J_up</ci>
<ci>V_myo</ci>
</apply>
<ci>V_NSR</ci>
</apply>
<apply>
<divide/>
<apply>
<times/>
<ci>J_tr</ci>
<ci>V_JSR</ci>
</apply>
<ci>V_NSR</ci>
</apply>
</apply>
</apply>
</math>
</component>
<component name="standard_ionic_concentrations">
<variable units="millimolar" public_interface="out" name="Na_o" initial_value="140"/>
<variable units="millimolar" public_interface="out" name="Ca_o" initial_value="1.2"/>
<variable units="millimolar" public_interface="out" name="K_o" initial_value="5.4"/>
</component>
<component cmeta:id="eqn1" name="membrane_fibro">
<variable units="millivolt" public_interface="out" cmeta:id="membrane_fibro_V_fibro" name="V_fibro"/>
<variable units="microF" name="Cm" initial_value="4.5e-6"/>
<variable units="nanoA" public_interface="in" name="I_b"/>
<variable units="nanoA" public_interface="in" name="I_Kir"/>
<variable units="nanoA" public_interface="in" name="I_Shkr"/>
<variable units="nanoA" public_interface="in" name="I_inter"/>
<variable units="second" public_interface="in" name="time"/>
<variable units="millivolt" name="VmReal" initial_value="-80.00"/>
<math xmlns="http://www.w3.org/1998/Math/MathML">
<apply>
<eq/>
<ci>V_fibro</ci>
<piecewise>
<piece>
<cn cellml:units="millivolt">1e-7</cn>
<apply>
<lt/>
<apply>
<abs/>
<ci>VmReal</ci>
</apply>
<cn cellml:units="millivolt">1e-7</cn>
</apply>
</piece>
<otherwise>
<ci>VmReal</ci>
</otherwise>
</piecewise>
</apply>
<apply>
<eq/>
<apply>
<diff/>
<bvar>
<ci>time</ci>
</bvar>
<ci>VmReal</ci>
</apply>
<apply>
<divide/>
<apply>
<minus/>
<apply>
<plus/>
<ci>I_Kir</ci>
<ci>I_Shkr</ci>
<ci>I_b</ci>
<ci>I_inter</ci>
</apply>
</apply>
<ci>Cm</ci>
</apply>
</apply>
</math>
</component>
<component cmeta:id="eqn2" name="I_Kir">
<variable units="nanoA" public_interface="out" cmeta:id="I_Kir_I_Kir" name="I_Kir"/>
<variable units="microS" name="GKir" initial_value="1e-3"/>
<variable units="dimensionless" name="aKir" initial_value="0.94"/>
<variable units="dimensionless" name="bKir" initial_value="1.26"/>
<variable units="millivolt" name="EK"/>
<variable units="dimensionless" name="OKir"/>
<variable units="second" public_interface="in" name="time"/>
<variable units="millivolt" public_interface="in" name="V_fibro"/>
<variable units="millijoule_per_mole_kelvin" public_interface="in" name="R"/>
<variable units="kelvin" public_interface="in" name="T"/>
<variable units="coulomb_per_mole" public_interface="in" name="F"/>
<variable units="millimolar" public_interface="in" name="Ko"/>
<variable units="millimolar" public_interface="in" name="Ki"/>
<math xmlns="http://www.w3.org/1998/Math/MathML">
<apply>
<eq/>
<ci>I_Kir</ci>
<apply>
<times/>
<ci>GKir</ci>
<ci>OKir</ci>
<apply>
<root/>
<apply>
<times/>
<ci>Ko</ci>
<cn cellml:units="per_millimolar">1e-3</cn>
</apply>
</apply>
<apply>
<minus/>
<ci>V_fibro</ci>
<ci>EK</ci>
</apply>
</apply>
</apply>
<apply>
<eq/>
<ci>OKir</ci>
<apply>
<divide/>
<cn cellml:units="dimensionless">1</cn>
<apply>
<plus/>
<ci>aKir</ci>
<apply>
<exp/>
<apply>
<divide/>
<apply>
<times/>
<ci>bKir</ci>
<apply>
<minus/>
<ci>V_fibro</ci>
<ci>EK</ci>
</apply>
<ci>F</ci>
</apply>
<apply>
<times/>
<ci>R</ci>
<ci>T</ci>
</apply>
</apply>
</apply>
</apply>
</apply>
</apply>
<apply>
<eq/>
<ci>EK</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 cmeta:id="eqn4" name="I_Shkr">
<variable units="nanoA" public_interface="out" cmeta:id="I_Shkr_I_Shkr" name="I_Shkr"/>
<variable units="microlitre_per_second" name="PShkr" initial_value="5.4e-9"/>
<variable units="dimensionless" name="C0ShkrReal" initial_value="9.11e-1"/>
<variable units="dimensionless" name="C1ShkrReal" initial_value="8.57e-2"/>
<variable units="dimensionless" name="C2ShkrReal" initial_value="3.02e-3"/>
<variable units="dimensionless" name="C3ShkrReal" initial_value="4.74e-5"/>
<variable units="dimensionless" name="C4ShkrReal" initial_value="2.79e-7"/>
<variable units="dimensionless" name="OShkrReal" initial_value="0"/>
<variable units="dimensionless" name="C0Shkr"/>
<variable units="dimensionless" name="C1Shkr"/>
<variable units="dimensionless" name="C2Shkr"/>
<variable units="dimensionless" name="C3Shkr"/>
<variable units="dimensionless" name="C4Shkr"/>
<variable units="dimensionless" name="OShkr"/>
<variable units="per_second" name="kv"/>
<variable units="per_second" name="k_v"/>
<variable units="per_second" name="kv0" initial_value="30"/>
<variable units="dimensionless" name="zv" initial_value="1.28"/>
<variable units="per_second" name="k_v0" initial_value="2"/>
<variable units="dimensionless" name="z_v" initial_value="-1.53"/>
<variable units="per_second" name="ko" initial_value="77"/>
<variable units="per_second" name="k_o" initial_value="18"/>
<variable units="second" public_interface="in" name="time"/>
<variable units="millivolt" public_interface="in" name="V_fibro"/>
<variable units="millijoule_per_mole_kelvin" public_interface="in" name="R"/>
<variable units="kelvin" public_interface="in" name="T"/>
<variable units="coulomb_per_mole" public_interface="in" name="F"/>
<variable units="millimolar" public_interface="in" name="Ko"/>
<variable units="millimolar" public_interface="in" name="Ki"/>
<math xmlns="http://www.w3.org/1998/Math/MathML">
<apply>
<eq/>
<ci>I_Shkr</ci>
<apply>
<divide/>
<apply>
<times/>
<apply>
<divide/>
<apply>
<times/>
<ci>PShkr</ci>
<ci>OShkr</ci>
<ci>V_fibro</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/>
<ci>Ki</ci>
<apply>
<times/>
<ci>Ko</ci>
<apply>
<exp/>
<apply>
<divide/>
<apply>
<times/>
<apply>
<minus/>
<ci>V_fibro</ci>
</apply>
<ci>F</ci>
</apply>
<apply>
<times/>
<ci>R</ci>
<ci>T</ci>
</apply>
</apply>
</apply>
</apply>
</apply>
</apply>
<apply>
<minus/>
<cn cellml:units="dimensionless">1</cn>
<apply>
<exp/>
<apply>
<divide/>
<apply>
<times/>
<apply>
<minus/>
<ci>V_fibro</ci>
</apply>
<ci>F</ci>
</apply>
<apply>
<times/>
<ci>R</ci>
<ci>T</ci>
</apply>
</apply>
</apply>
</apply>
</apply>
</apply>
<apply>
<eq/>
<ci>C0Shkr</ci>
<piecewise>
<piece>
<cn cellml:units="dimensionless">0</cn>
<apply>
<lt/>
<ci>C0ShkrReal</ci>
<cn cellml:units="dimensionless">0</cn>
</apply>
</piece>
<piece>
<cn cellml:units="dimensionless">1</cn>
<apply>
<gt/>
<ci>C0ShkrReal</ci>
<cn cellml:units="dimensionless">1</cn>
</apply>
</piece>
<otherwise>
<ci>C0ShkrReal</ci>
</otherwise>
</piecewise>
</apply>
<apply>
<eq/>
<ci>C1Shkr</ci>
<piecewise>
<piece>
<cn cellml:units="dimensionless">0</cn>
<apply>
<lt/>
<ci>C1ShkrReal</ci>
<cn cellml:units="dimensionless">0</cn>
</apply>
</piece>
<piece>
<cn cellml:units="dimensionless">1</cn>
<apply>
<gt/>
<ci>C1ShkrReal</ci>
<cn cellml:units="dimensionless">1</cn>
</apply>
</piece>
<otherwise>
<ci>C1ShkrReal</ci>
</otherwise>
</piecewise>
</apply>
<apply>
<eq/>
<ci>C2Shkr</ci>
<piecewise>
<piece>
<cn cellml:units="dimensionless">0</cn>
<apply>
<lt/>
<ci>C2ShkrReal</ci>
<cn cellml:units="dimensionless">0</cn>
</apply>
</piece>
<piece>
<cn cellml:units="dimensionless">1</cn>
<apply>
<gt/>
<ci>C2ShkrReal</ci>
<cn cellml:units="dimensionless">1</cn>
</apply>
</piece>
<otherwise>
<ci>C2ShkrReal</ci>
</otherwise>
</piecewise>
</apply>
<apply>
<eq/>
<ci>C3Shkr</ci>
<piecewise>
<piece>
<cn cellml:units="dimensionless">0</cn>
<apply>
<lt/>
<ci>C3ShkrReal</ci>
<cn cellml:units="dimensionless">0</cn>
</apply>
</piece>
<piece>
<cn cellml:units="dimensionless">1</cn>
<apply>
<gt/>
<ci>C3ShkrReal</ci>
<cn cellml:units="dimensionless">1</cn>
</apply>
</piece>
<otherwise>
<ci>C3ShkrReal</ci>
</otherwise>
</piecewise>
</apply>
<apply>
<eq/>
<ci>C4Shkr</ci>
<piecewise>
<piece>
<cn cellml:units="dimensionless">0</cn>
<apply>
<lt/>
<ci>C4ShkrReal</ci>
<cn cellml:units="dimensionless">0</cn>
</apply>
</piece>
<piece>
<cn cellml:units="dimensionless">1</cn>
<apply>
<gt/>
<ci>C4ShkrReal</ci>
<cn cellml:units="dimensionless">1</cn>
</apply>
</piece>
<otherwise>
<ci>C4ShkrReal</ci>
</otherwise>
</piecewise>
</apply>
<apply>
<eq/>
<ci>OShkr</ci>
<piecewise>
<piece>
<cn cellml:units="dimensionless">0</cn>
<apply>
<lt/>
<ci>OShkrReal</ci>
<cn cellml:units="dimensionless">0</cn>
</apply>
</piece>
<piece>
<cn cellml:units="dimensionless">1</cn>
<apply>
<gt/>
<ci>OShkrReal</ci>
<cn cellml:units="dimensionless">1</cn>
</apply>
</piece>
<otherwise>
<ci>OShkrReal</ci>
</otherwise>
</piecewise>
</apply>
<apply>
<eq/>
<ci>kv</ci>
<apply>
<times/>
<ci>kv0</ci>
<apply>
<exp/>
<apply>
<divide/>
<apply>
<times/>
<ci>V_fibro</ci>
<ci>zv</ci>
<ci>F</ci>
</apply>
<apply>
<times/>
<ci>R</ci>
<ci>T</ci>
</apply>
</apply>
</apply>
</apply>
</apply>
<apply>
<eq/>
<ci>k_v</ci>
<apply>
<times/>
<ci>k_v0</ci>
<apply>
<exp/>
<apply>
<divide/>
<apply>
<times/>
<ci>V_fibro</ci>
<ci>z_v</ci>
<ci>F</ci>
</apply>
<apply>
<times/>
<ci>R</ci>
<ci>T</ci>
</apply>
</apply>
</apply>
</apply>
</apply>
<apply>
<eq/>
<apply>
<diff/>
<bvar>
<ci>time</ci>
</bvar>
<ci>C0ShkrReal</ci>
</apply>
<apply>
<minus/>
<apply>
<times/>
<ci>k_v</ci>
<ci>C1Shkr</ci>
</apply>
<apply>
<times/>
<cn cellml:units="dimensionless">4</cn>
<ci>kv</ci>
<ci>C0Shkr</ci>
</apply>
</apply>
</apply>
<apply>
<eq/>
<apply>
<diff/>
<bvar>
<ci>time</ci>
</bvar>
<ci>C1ShkrReal</ci>
</apply>
<apply>
<minus/>
<apply>
<plus/>
<apply>
<times/>
<cn cellml:units="dimensionless">2</cn>
<ci>k_v</ci>
<ci>C2Shkr</ci>
</apply>
<apply>
<times/>
<cn cellml:units="dimensionless">4</cn>
<ci>kv</ci>
<ci>C0Shkr</ci>
</apply>
</apply>
<apply>
<times/>
<apply>
<plus/>
<apply>
<times/>
<cn cellml:units="dimensionless">3</cn>
<ci>kv</ci>
</apply>
<ci>k_v</ci>
</apply>
<ci>C1Shkr</ci>
</apply>
</apply>
</apply>
<apply>
<eq/>
<apply>
<diff/>
<bvar>
<ci>time</ci>
</bvar>
<ci>C2ShkrReal</ci>
</apply>
<apply>
<minus/>
<apply>
<plus/>
<apply>
<times/>
<cn cellml:units="dimensionless">3</cn>
<ci>k_v</ci>
<ci>C3Shkr</ci>
</apply>
<apply>
<times/>
<cn cellml:units="dimensionless">3</cn>
<ci>kv</ci>
<ci>C1Shkr</ci>
</apply>
</apply>
<apply>
<times/>
<apply>
<plus/>
<apply>
<times/>
<cn cellml:units="dimensionless">2</cn>
<ci>kv</ci>
</apply>
<apply>
<times/>
<cn cellml:units="dimensionless">2</cn>
<ci>k_v</ci>
</apply>
</apply>
<ci>C2Shkr</ci>
</apply>
</apply>
</apply>
<apply>
<eq/>
<apply>
<diff/>
<bvar>
<ci>time</ci>
</bvar>
<ci>C3ShkrReal</ci>
</apply>
<apply>
<minus/>
<apply>
<plus/>
<apply>
<times/>
<cn cellml:units="dimensionless">4</cn>
<ci>k_v</ci>
<ci>C4Shkr</ci>
</apply>
<apply>
<times/>
<cn cellml:units="dimensionless">2</cn>
<ci>kv</ci>
<ci>C2Shkr</ci>
</apply>
</apply>
<apply>
<times/>
<apply>
<plus/>
<ci>kv</ci>
<apply>
<times/>
<cn cellml:units="dimensionless">3</cn>
<ci>k_v</ci>
</apply>
</apply>
<ci>C3Shkr</ci>
</apply>
</apply>
</apply>
<apply>
<eq/>
<apply>
<diff/>
<bvar>
<ci>time</ci>
</bvar>
<ci>C4ShkrReal</ci>
</apply>
<apply>
<minus/>
<apply>
<plus/>
<apply>
<times/>
<ci>k_o</ci>
<ci>OShkr</ci>
</apply>
<apply>
<times/>
<ci>kv</ci>
<ci>C3Shkr</ci>
</apply>
</apply>
<apply>
<times/>
<apply>
<plus/>
<ci>ko</ci>
<apply>
<times/>
<cn cellml:units="dimensionless">4</cn>
<ci>k_v</ci>
</apply>
</apply>
<ci>C4Shkr</ci>
</apply>
</apply>
</apply>
<apply>
<eq/>
<apply>
<diff/>
<bvar>
<ci>time</ci>
</bvar>
<ci>OShkrReal</ci>
</apply>
<apply>
<minus/>
<apply>
<times/>
<ci>ko</ci>
<ci>C4Shkr</ci>
</apply>
<apply>
<times/>
<ci>k_o</ci>
<ci>OShkr</ci>
</apply>
</apply>
</apply>
</math>
</component>
<component cmeta:id="eqn14" name="I_b">
<variable units="nanoA" public_interface="out" cmeta:id="I_b_I_b" name="I_b"/>
<variable units="microS" name="Gb" initial_value="6.9e-6"/>
<variable units="millivolt" name="Eb" initial_value="0"/>
<variable units="second" public_interface="in" name="time"/>
<variable units="millivolt" public_interface="in" name="V_fibro"/>
<math xmlns="http://www.w3.org/1998/Math/MathML">
<apply>
<eq/>
<ci>I_b</ci>
<apply>
<times/>
<ci>Gb</ci>
<apply>
<minus/>
<ci>V_fibro</ci>
<ci>Eb</ci>
</apply>
</apply>
</apply>
</math>
</component>
<component name="I_inter">
<variable units="nanoA" public_interface="out" cmeta:id="I_inter_I_inter_fibro" name="I_inter_fibro"/>
<variable units="nanoA" public_interface="out" name="I_inter_myo"/>
<variable units="ohm" name="R_mf" initial_value="100e6"/>
<variable units="dimensionless" name="number_of_fibroblasts" initial_value="1"/>
<variable units="millivolt" public_interface="in" name="V_fibro"/>
<variable units="millivolt" public_interface="in" name="V"/>
<math xmlns="http://www.w3.org/1998/Math/MathML">
<apply>
<eq/>
<ci>I_inter_fibro</ci>
<apply>
<divide/>
<apply>
<times/>
<cn cellml:units="nanoA_per_milliA">1e+06</cn>
<apply>
<minus/>
<ci>V_fibro</ci>
<ci>V</ci>
</apply>
</apply>
<ci>R_mf</ci>
</apply>
</apply>
<apply>
<eq/>
<ci>I_inter_myo</ci>
<apply>
<times/>
<cn cellml:units="dimensionless">-1</cn>
<ci>I_inter_fibro</ci>
<ci>number_of_fibroblasts</ci>
</apply>
</apply>
</math>
</component>
<group>
<relationship_ref relationship="containment"/>
<component_ref component="membrane">
<component_ref component="I_Kir"/>
<component_ref component="I_Shkr"/>
<component_ref component="I_b"/>
<component_ref component="I_inter"/>
<component_ref component="sodium_current">
<component_ref component="sodium_current_m_gate"/>
<component_ref component="sodium_current_h_gate"/>
<component_ref component="sodium_current_j_gate"/>
</component_ref>
<component_ref component="L_type_Ca_channel">
<component_ref component="L_type_Ca_channel_d_gate"/>
<component_ref component="L_type_Ca_channel_f_11_gate"/>
<component_ref component="L_type_Ca_channel_f_12_gate"/>
<component_ref component="L_type_Ca_channel_Ca_inact_gate"/>
</component_ref>
<component_ref component="Ca_independent_transient_outward_K_current">
<component_ref component="Ca_independent_transient_outward_K_current_r_gate"/>
<component_ref component="Ca_independent_transient_outward_K_current_s_gate"/>
<component_ref component="Ca_independent_transient_outward_K_current_s_slow_gate"/>
</component_ref>
<component_ref component="steady_state_outward_K_current">
<component_ref component="steady_state_outward_K_current_r_ss_gate"/>
<component_ref component="steady_state_outward_K_current_s_ss_gate"/>
</component_ref>
<component_ref component="inward_rectifier"/>
<component_ref component="hyperpolarisation_activated_current">
<component_ref component="hyperpolarisation_activated_current_y_gate"/>
</component_ref>
<component_ref component="background_currents"/>
<component_ref component="sodium_potassium_pump"/>
<component_ref component="sarcolemmal_calcium_pump_current"/>
<component_ref component="Na_Ca_ion_exchanger_current"/>
<component_ref component="SR_Ca_release_channel"/>
<component_ref component="SERCA2a_pump"/>
<component_ref component="intracellular_and_SR_Ca_fluxes"/>
<component_ref component="intracellular_ion_concentrations"/>
<component_ref component="standard_ionic_concentrations"/>
</component_ref>
</group>
<group>
<relationship_ref relationship="encapsulation"/>
<component_ref component="sodium_current">
<component_ref component="sodium_current_m_gate"/>
<component_ref component="sodium_current_h_gate"/>
<component_ref component="sodium_current_j_gate"/>
</component_ref>
<component_ref component="L_type_Ca_channel">
<component_ref component="L_type_Ca_channel_d_gate"/>
<component_ref component="L_type_Ca_channel_f_11_gate"/>
<component_ref component="L_type_Ca_channel_f_12_gate"/>
<component_ref component="L_type_Ca_channel_Ca_inact_gate"/>
</component_ref>
<component_ref component="Ca_independent_transient_outward_K_current">
<component_ref component="Ca_independent_transient_outward_K_current_r_gate"/>
<component_ref component="Ca_independent_transient_outward_K_current_s_gate"/>
<component_ref component="Ca_independent_transient_outward_K_current_s_slow_gate"/>
</component_ref>
<component_ref component="steady_state_outward_K_current">
<component_ref component="steady_state_outward_K_current_r_ss_gate"/>
<component_ref component="steady_state_outward_K_current_s_ss_gate"/>
</component_ref>
<component_ref component="hyperpolarisation_activated_current">
<component_ref component="hyperpolarisation_activated_current_y_gate"/>
</component_ref>
</group>
<connection>
<map_components component_2="environment" component_1="membrane"/>
<map_variables variable_2="time" variable_1="time"/>
</connection>
<connection>
<map_components component_2="environment" component_1="sodium_current"/>
<map_variables variable_2="time" variable_1="time"/>
</connection>
<connection>
<map_components component_2="environment" component_1="L_type_Ca_channel"/>
<map_variables variable_2="time" variable_1="time"/>
</connection>
<connection>
<map_components component_2="environment" component_1="Ca_independent_transient_outward_K_current"/>
<map_variables variable_2="time" variable_1="time"/>
</connection>
<connection>
<map_components component_2="environment" component_1="steady_state_outward_K_current"/>
<map_variables variable_2="time" variable_1="time"/>
</connection>
<connection>
<map_components component_2="environment" component_1="inward_rectifier"/>
<map_variables variable_2="time" variable_1="time"/>
</connection>
<connection>
<map_components component_2="environment" component_1="hyperpolarisation_activated_current"/>
<map_variables variable_2="time" variable_1="time"/>
</connection>
<connection>
<map_components component_2="environment" component_1="background_currents"/>
<map_variables variable_2="time" variable_1="time"/>
</connection>
<connection>
<map_components component_2="environment" component_1="sodium_potassium_pump"/>
<map_variables variable_2="time" variable_1="time"/>
</connection>
<connection>
<map_components component_2="environment" component_1="sarcolemmal_calcium_pump_current"/>
<map_variables variable_2="time" variable_1="time"/>
</connection>
<connection>
<map_components component_2="environment" component_1="Na_Ca_ion_exchanger_current"/>
<map_variables variable_2="time" variable_1="time"/>
</connection>
<connection>
<map_components component_2="environment" component_1="SR_Ca_release_channel"/>
<map_variables variable_2="time" variable_1="time"/>
</connection>
<connection>
<map_components component_2="environment" component_1="SERCA2a_pump"/>
<map_variables variable_2="time" variable_1="time"/>
</connection>
<connection>
<map_components component_2="environment" component_1="intracellular_and_SR_Ca_fluxes"/>
<map_variables variable_2="time" variable_1="time"/>
</connection>
<connection>
<map_components component_2="environment" component_1="intracellular_ion_concentrations"/>
<map_variables variable_2="time" variable_1="time"/>
</connection>
<connection>
<map_components component_2="sodium_current" component_1="membrane"/>
<map_variables variable_2="V" variable_1="V"/>
<map_variables variable_2="R" variable_1="R"/>
<map_variables variable_2="T" variable_1="T"/>
<map_variables variable_2="F" variable_1="F"/>
<map_variables variable_2="i_Na" variable_1="i_Na"/>
</connection>
<connection>
<map_components component_2="L_type_Ca_channel" component_1="membrane"/>
<map_variables variable_2="V" variable_1="V"/>
<map_variables variable_2="i_Ca_L" variable_1="i_Ca_L"/>
</connection>
<connection>
<map_components component_2="Ca_independent_transient_outward_K_current" component_1="membrane"/>
<map_variables variable_2="V" variable_1="V"/>
<map_variables variable_2="i_t" variable_1="i_t"/>
<map_variables variable_2="R" variable_1="R"/>
<map_variables variable_2="T" variable_1="T"/>
<map_variables variable_2="F" variable_1="F"/>
</connection>
<connection>
<map_components component_2="steady_state_outward_K_current" component_1="membrane"/>
<map_variables variable_2="V" variable_1="V"/>
<map_variables variable_2="i_ss" variable_1="i_ss"/>
</connection>
<connection>
<map_components component_2="inward_rectifier" component_1="membrane"/>
<map_variables variable_2="V" variable_1="V"/>
<map_variables variable_2="i_K1" variable_1="i_K1"/>
<map_variables variable_2="R" variable_1="R"/>
<map_variables variable_2="T" variable_1="T"/>
<map_variables variable_2="F" variable_1="F"/>
</connection>
<connection>
<map_components component_2="hyperpolarisation_activated_current" component_1="membrane"/>
<map_variables variable_2="V" variable_1="V"/>
<map_variables variable_2="i_f" variable_1="i_f"/>
</connection>
<connection>
<map_components component_2="background_currents" component_1="membrane"/>
<map_variables variable_2="V" variable_1="V"/>
<map_variables variable_2="i_B" variable_1="i_B"/>
<map_variables variable_2="R" variable_1="R"/>
<map_variables variable_2="T" variable_1="T"/>
<map_variables variable_2="F" variable_1="F"/>
</connection>
<connection>
<map_components component_2="sodium_potassium_pump" component_1="membrane"/>
<map_variables variable_2="V" variable_1="V"/>
<map_variables variable_2="i_NaK" variable_1="i_NaK"/>
<map_variables variable_2="R" variable_1="R"/>
<map_variables variable_2="T" variable_1="T"/>
<map_variables variable_2="F" variable_1="F"/>
</connection>
<connection>
<map_components component_2="sarcolemmal_calcium_pump_current" component_1="membrane"/>
<map_variables variable_2="i_Ca_P" variable_1="i_Ca_P"/>
</connection>
<connection>
<map_components component_2="Na_Ca_ion_exchanger_current" component_1="membrane"/>
<map_variables variable_2="V" variable_1="V"/>
<map_variables variable_2="i_NaCa" variable_1="i_NaCa"/>
</connection>
<connection>
<map_components component_2="intracellular_ion_concentrations" component_1="membrane"/>
<map_variables variable_2="F" variable_1="F"/>
</connection>
<connection>
<map_components component_2="I_inter" component_1="membrane"/>
<map_variables variable_2="I_inter_myo" variable_1="I_inter"/>
<map_variables variable_2="V" variable_1="V"/>
</connection>
<connection>
<map_components component_2="intracellular_ion_concentrations" component_1="sodium_current"/>
<map_variables variable_2="i_Na" variable_1="i_Na"/>
<map_variables variable_2="Na_i" variable_1="Na_i"/>
</connection>
<connection>
<map_components component_2="background_currents" component_1="sodium_current"/>
<map_variables variable_2="E_Na" variable_1="E_Na"/>
</connection>
<connection>
<map_components component_2="hyperpolarisation_activated_current" component_1="sodium_current"/>
<map_variables variable_2="E_Na" variable_1="E_Na"/>
</connection>
<connection>
<map_components component_2="standard_ionic_concentrations" component_1="sodium_current"/>
<map_variables variable_2="Na_o" variable_1="Na_o"/>
</connection>
<connection>
<map_components component_2="standard_ionic_concentrations" component_1="background_currents"/>
<map_variables variable_2="Ca_o" variable_1="Ca_o"/>
</connection>
<connection>
<map_components component_2="intracellular_ion_concentrations" component_1="L_type_Ca_channel"/>
<map_variables variable_2="i_Ca_L" variable_1="i_Ca_L"/>
<map_variables variable_2="Ca_ss" variable_1="Ca_ss"/>
</connection>
<connection>
<map_components component_2="intracellular_ion_concentrations" component_1="Ca_independent_transient_outward_K_current"/>
<map_variables variable_2="i_t" variable_1="i_t"/>
<map_variables variable_2="K_i" variable_1="K_i"/>
</connection>
<connection>
<map_components component_2="steady_state_outward_K_current" component_1="Ca_independent_transient_outward_K_current"/>
<map_variables variable_2="E_K" variable_1="E_K"/>
</connection>
<connection>
<map_components component_2="inward_rectifier" component_1="Ca_independent_transient_outward_K_current"/>
<map_variables variable_2="E_K" variable_1="E_K"/>
</connection>
<connection>
<map_components component_2="hyperpolarisation_activated_current" component_1="Ca_independent_transient_outward_K_current"/>
<map_variables variable_2="E_K" variable_1="E_K"/>
</connection>
<connection>
<map_components component_2="background_currents" component_1="Ca_independent_transient_outward_K_current"/>
<map_variables variable_2="E_K" variable_1="E_K"/>
</connection>
<connection>
<map_components component_2="standard_ionic_concentrations" component_1="Ca_independent_transient_outward_K_current"/>
<map_variables variable_2="K_o" variable_1="K_o"/>
</connection>
<connection>
<map_components component_2="intracellular_ion_concentrations" component_1="steady_state_outward_K_current"/>
<map_variables variable_2="i_ss" variable_1="i_ss"/>
</connection>
<connection>
<map_components component_2="intracellular_ion_concentrations" component_1="inward_rectifier"/>
<map_variables variable_2="i_K1" variable_1="i_K1"/>
<map_variables variable_2="K_i" variable_1="K_i"/>
</connection>
<connection>
<map_components component_2="standard_ionic_concentrations" component_1="inward_rectifier"/>
<map_variables variable_2="K_o" variable_1="K_o"/>
</connection>
<connection>
<map_components component_2="intracellular_ion_concentrations" component_1="hyperpolarisation_activated_current"/>
<map_variables variable_2="i_f_Na" variable_1="i_f_Na"/>
<map_variables variable_2="i_f_K" variable_1="i_f_K"/>
</connection>
<connection>
<map_components component_2="intracellular_ion_concentrations" component_1="background_currents"/>
<map_variables variable_2="i_B_Na" variable_1="i_B_Na"/>
<map_variables variable_2="i_B_K" variable_1="i_B_K"/>
<map_variables variable_2="i_B_Ca" variable_1="i_B_Ca"/>
<map_variables variable_2="Ca_i" variable_1="Ca_i"/>
</connection>
<connection>
<map_components component_2="intracellular_ion_concentrations" component_1="sodium_potassium_pump"/>
<map_variables variable_2="i_NaK" variable_1="i_NaK"/>
<map_variables variable_2="Na_i" variable_1="Na_i"/>
</connection>
<connection>
<map_components component_2="standard_ionic_concentrations" component_1="sodium_potassium_pump"/>
<map_variables variable_2="K_o" variable_1="K_o"/>
<map_variables variable_2="Na_o" variable_1="Na_o"/>
</connection>
<connection>
<map_components component_2="intracellular_ion_concentrations" component_1="sarcolemmal_calcium_pump_current"/>
<map_variables variable_2="i_Ca_P" variable_1="i_Ca_P"/>
<map_variables variable_2="Ca_i" variable_1="Ca_i"/>
</connection>
<connection>
<map_components component_2="intracellular_ion_concentrations" component_1="Na_Ca_ion_exchanger_current"/>
<map_variables variable_2="Ca_i" variable_1="Ca_i"/>
<map_variables variable_2="Na_i" variable_1="Na_i"/>
<map_variables variable_2="i_NaCa" variable_1="i_NaCa"/>
</connection>
<connection>
<map_components component_2="standard_ionic_concentrations" component_1="Na_Ca_ion_exchanger_current"/>
<map_variables variable_2="Ca_o" variable_1="Ca_o"/>
<map_variables variable_2="Na_o" variable_1="Na_o"/>
</connection>
<connection>
<map_components component_2="intracellular_ion_concentrations" component_1="SR_Ca_release_channel"/>
<map_variables variable_2="J_rel" variable_1="J_rel"/>
<map_variables variable_2="Ca_ss" variable_1="Ca_ss"/>
<map_variables variable_2="Ca_JSR" variable_1="Ca_JSR"/>
</connection>
<connection>
<map_components component_2="intracellular_ion_concentrations" component_1="SERCA2a_pump"/>
<map_variables variable_2="J_up" variable_1="J_up"/>
<map_variables variable_2="Ca_i" variable_1="Ca_i"/>
<map_variables variable_2="Ca_NSR" variable_1="Ca_NSR"/>
</connection>
<connection>
<map_components component_2="intracellular_ion_concentrations" component_1="intracellular_and_SR_Ca_fluxes"/>
<map_variables variable_2="J_tr" variable_1="J_tr"/>
<map_variables variable_2="J_xfer" variable_1="J_xfer"/>
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<rdf:value>Dimensional inconsistencies have been fixed.
Variables V_myo, V_JSR, V_SS, V_NSR (component intracellular_ion_concentrations) units changed from picolitres to microlitres, variables changed to match those in Version 08 of Pandit 2001 model.
RHS multiplied by scaling factor of 1e6 with units nanoamps/milliamps in equation defining variable I_inter_fibro in component 'I_inter' in order to address inconsistencies in unit handling between JSim vs PCEnv and COR
Model now runs to give the same results in PCEnv, COR and Jsim
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<rdf:value>Dimensional inconsistencies have been fixed.
Variables V_myo, V_JSR, V_SS, V_NSR (component intracellular_ion_concentrations) units changed from picolitres to microlitres, variables changed to match those in Version 08 of Pandit 2001 model.
RHS multiplied by scaling factor of 1e6 with units nanoamps/milliamps in equation defining variable I_inter_fibro in component 'I_inter'
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<dcterms:W3CDTF>2008-01-00 00:00</dcterms:W3CDTF>
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<rdf:value>This CellML version of the model runs in PCEnv, COR and JSim to recreate the results in the published paper. The units have been checked and are consistent, and we would like to thank Frank Sachse, the original model author, for his advice and assistance in getting the CellML version of this model working. This particular CellML model represents the coupled fibroblast-myocyte model.</rdf:value>
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