- Author:
- pmr2.import <nobody@models.cellml.org>
- Date:
- 2008-06-17 13:24:40+12:00
- Desc:
- committing version02 of hund_rudy_2004
- Permanent Source URI:
- https://models.fieldml.org/workspace/hund_rudy_2004/rawfile/9a4f377441f3e619af63e03f6283107d1cb27ec9/hund_rudy_2004_a.cellml
<?xml version='1.0' encoding='utf-8'?>
<!--
This CellML file was generated on 28/01/2008 at 16:45:18 using:
COR (0.9.31.863)
Copyright 2002-2008 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#" cmeta:id="hund_rudy_2004_version02" name="hund_rudy_2004_version02">
<documentation xmlns="http://cellml.org/tmp-documentation">
<article>
<articleinfo>
<author>
<firstname>Penny</firstname>
<surname>Noble</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 has been checked in COR. The units are consistent and the model runs to recreate the published results. The parameter 'tissue' has been added to switch between the original (default value 0) and 'tissue' (any other value, for example 1) models.
</para>
</section>
<sect1 id="sec_structure">
<title>Model Structure</title>
<para>
In the paper described here, Thomas Hund and Yoram Rudy present a detailed, and physiologically realistic, mathematical model of a canine ventricular cell. Model simulations are able to recreate the rate-dependent phenomena associated with ion-channel kinetics, action potential properties, and calcium ion handling. The model is based on an epicardial myocyte because these cells contain the largest transient outward potassium current (when compared with endocardial or midmyocardial myocytes). The calcium/calmodulin-dependent protein kinase (CaMKII) regulatory pathway was embedded within the electrophysiological model, incorporating calcium-release formulation, calcium subspace, and dynamic chloride handling. Results from the model simulations revealed CaMKII is an important determinant of the rate dependence of the calcium transient, but not of the action potential duration, which depends instead on the ion-channel kinetics.
</para>
<informalfigure float="0" id="fig_reaction_diagram">
<mediaobject>
<imageobject>
<objectinfo>
<title>model diagram</title>
</objectinfo>
<imagedata fileref="hund_2004.png"/>
</imageobject>
</mediaobject>
<caption>Schematic diagram of the Hund and Rudy Canine Ventricular Cell Model.</caption>
</informalfigure>
<para>
The complete original paper reference is cited below:
</para>
<para>
<ulink url="http://circ.ahajournals.org/cgi/content/abstract/110/20/3168">Rate dependence and regulation of action potential and calcium transient in a canine cardiac ventricular cell model</ulink>, Thomas J. Hund and Yoram Rudy, 2004, <ulink url="http://circ.ahajournals.org/">
<emphasis>Circulation</emphasis>,
</ulink> 110, 3168-3174. (<ulink url="http://circ.ahajournals.org/cgi/content/full/110/20/3168">Full text</ulink> and <ulink url="http://circ.ahajournals.org/cgi/reprint/110/20/3168">PDF</ulink> versions of the article are available to journal subscribers on the <emphasis>Circulation</emphasis> website.) <ulink url="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=AbstractPlus&list_uids=15505083&query_hl=1&itool=pubmed_docsum">PubMed ID: 15505083</ulink>
</para>
</sect1>
</article>
</documentation>
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<ci>H</ci>
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<ci>H</ci>
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<eq/>
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<diff/>
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</bvar>
<ci>m</ci>
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<minus/>
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<times/>
<ci>am</ci>
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<minus/>
<cn cellml:units="dimensionless">1</cn>
<ci>m</ci>
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<times/>
<ci>bm</ci>
<ci>m</ci>
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<eq/>
<apply>
<diff/>
<bvar>
<ci>time</ci>
</bvar>
<ci>J</ci>
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<minus/>
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<times/>
<ci>aj</ci>
<apply>
<minus/>
<cn cellml:units="dimensionless">1</cn>
<ci>J</ci>
</apply>
</apply>
<apply>
<times/>
<ci>bj</ci>
<ci>J</ci>
</apply>
</apply>
</apply>
</math>
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<component name="ICaL">
<variable units="mV" public_interface="in" name="V"/>
<variable units="C_per_mole" public_interface="in" name="F"/>
<variable units="per_mV" public_interface="in" name="FonRT"/>
<variable units="ms" public_interface="in" name="time"/>
<variable units="dimensionless" public_interface="in" name="tissue"/>
<variable units="mM" public_interface="in" name="Ca_o"/>
<variable units="mM" public_interface="in" name="Ca_ss"/>
<variable units="dimensionless" name="d" initial_value="0.00000164013"/>
<variable units="dimensionless" name="dp" initial_value="8.98230672628"/>
<variable units="dimensionless" name="f" initial_value="0.999961508634"/>
<variable units="dimensionless" name="fca" initial_value="0.97836624923"/>
<variable units="dimensionless" name="fca2" initial_value="0.893052931249"/>
<variable units="dimensionless" name="f2" initial_value="0.992234519148"/>
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<variable units="dimensionless" name="gacai" initial_value="1"/>
<variable units="dimensionless" name="gacao" initial_value="0.341"/>
<variable units="dimensionless" public_interface="in" name="CaMKactive"/>
<variable units="uA_per_uF" public_interface="out" name="ibarca"/>
<variable units="dimensionless" name="dss"/>
<variable units="ms" name="taud"/>
<variable units="dimensionless" name="fss"/>
<variable units="dimensionless" name="f2ss"/>
<variable units="ms" name="tauf"/>
<variable units="ms" name="tauf2"/>
<variable units="dimensionless" name="dpss"/>
<variable units="dimensionless" name="fcass"/>
<variable units="dimensionless" name="fca2ss"/>
<variable units="ms" name="taufca"/>
<variable units="ms" name="taufca2"/>
<variable units="uA_per_uF" public_interface="out" name="ICaL"/>
<math xmlns="http://www.w3.org/1998/Math/MathML">
<apply>
<eq/>
<ci>ibarca</ci>
<apply>
<divide/>
<apply>
<times/>
<ci>pca</ci>
<cn cellml:units="dimensionless">4</cn>
<apply>
<minus/>
<ci>V</ci>
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</apply>
<ci>F</ci>
<ci>FonRT</ci>
<apply>
<minus/>
<apply>
<times/>
<ci>gacai</ci>
<ci>Ca_ss</ci>
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<exp/>
<apply>
<times/>
<cn cellml:units="dimensionless">2</cn>
<apply>
<minus/>
<ci>V</ci>
<cn cellml:units="mV">15</cn>
</apply>
<ci>FonRT</ci>
</apply>
</apply>
</apply>
<apply>
<times/>
<ci>gacao</ci>
<ci>Ca_o</ci>
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</apply>
</apply>
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<minus/>
<apply>
<exp/>
<apply>
<times/>
<cn cellml:units="dimensionless">2</cn>
<apply>
<minus/>
<ci>V</ci>
<cn cellml:units="mV">15</cn>
</apply>
<ci>FonRT</ci>
</apply>
</apply>
<cn cellml:units="dimensionless">1</cn>
</apply>
</apply>
</apply>
<apply>
<eq/>
<ci>ICaL</ci>
<piecewise>
<piece>
<apply>
<times/>
<apply>
<power/>
<ci>d</ci>
<ci>dp</ci>
</apply>
<ci>f</ci>
<ci>f2</ci>
<ci>fca</ci>
<ci>fca2</ci>
<ci>ibarca</ci>
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<apply>
<eq/>
<ci>tissue</ci>
<cn cellml:units="dimensionless">0</cn>
</apply>
</piece>
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<apply>
<times/>
<ci>d</ci>
<ci>f</ci>
<ci>f2</ci>
<ci>fca</ci>
<ci>fca2</ci>
<ci>ibarca</ci>
</apply>
</otherwise>
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<apply>
<eq/>
<ci>dss</ci>
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<divide/>
<cn cellml:units="dimensionless">1</cn>
<apply>
<plus/>
<cn cellml:units="dimensionless">1</cn>
<apply>
<exp/>
<apply>
<divide/>
<apply>
<minus/>
<apply>
<minus/>
<ci>V</ci>
<cn cellml:units="mV">4</cn>
</apply>
</apply>
<cn cellml:units="mV">6.74</cn>
</apply>
</apply>
</apply>
</apply>
</apply>
<apply>
<eq/>
<ci>taud</ci>
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<plus/>
<cn cellml:units="ms">0.59</cn>
<apply>
<divide/>
<apply>
<times/>
<cn cellml:units="ms">0.8</cn>
<apply>
<exp/>
<apply>
<times/>
<cn cellml:units="per_mV">0.052</cn>
<apply>
<plus/>
<ci>V</ci>
<cn cellml:units="mV">13</cn>
</apply>
</apply>
</apply>
</apply>
<apply>
<plus/>
<cn cellml:units="dimensionless">1</cn>
<apply>
<exp/>
<apply>
<times/>
<cn cellml:units="per_mV">0.132</cn>
<apply>
<plus/>
<ci>V</ci>
<cn cellml:units="mV">13</cn>
</apply>
</apply>
</apply>
</apply>
</apply>
</apply>
</apply>
<apply>
<eq/>
<ci>fss</ci>
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<plus/>
<apply>
<divide/>
<cn cellml:units="dimensionless">0.7</cn>
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<plus/>
<cn cellml:units="dimensionless">1</cn>
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<exp/>
<apply>
<divide/>
<apply>
<plus/>
<ci>V</ci>
<cn cellml:units="mV">17.12</cn>
</apply>
<cn cellml:units="mV">7</cn>
</apply>
</apply>
</apply>
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<cn cellml:units="dimensionless">0.3</cn>
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<eq/>
<ci>f2ss</ci>
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<plus/>
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<divide/>
<cn cellml:units="dimensionless">0.77</cn>
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<plus/>
<cn cellml:units="dimensionless">1</cn>
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<apply>
<divide/>
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<plus/>
<ci>V</ci>
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<cn cellml:units="mV">7</cn>
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<cn cellml:units="dimensionless">0.23</cn>
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<apply>
<eq/>
<ci>tauf</ci>
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<divide/>
<cn cellml:units="ms">1</cn>
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<plus/>
<apply>
<times/>
<cn cellml:units="dimensionless">0.2411</cn>
<apply>
<exp/>
<apply>
<minus/>
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<power/>
<apply>
<times/>
<cn cellml:units="per_mV">0.045</cn>
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<minus/>
<ci>V</ci>
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<cn cellml:units="dimensionless">2</cn>
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<apply>
<eq/>
<ci>tauf2</ci>
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<divide/>
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<apply>
<plus/>
<apply>
<times/>
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<apply>
<exp/>
<apply>
<minus/>
<apply>
<power/>
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<times/>
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<apply>
<minus/>
<ci>V</ci>
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<cn cellml:units="dimensionless">2</cn>
</apply>
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<eq/>
<ci>dpss</ci>
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<minus/>
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<divide/>
<cn cellml:units="dimensionless">8</cn>
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<plus/>
<cn cellml:units="dimensionless">1</cn>
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<exp/>
<apply>
<divide/>
<apply>
<minus/>
<apply>
<plus/>
<ci>V</ci>
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</apply>
</apply>
<cn cellml:units="mV">3.4</cn>
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</apply>
</apply>
</apply>
</apply>
</apply>
<apply>
<eq/>
<ci>fcass</ci>
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<plus/>
<apply>
<divide/>
<cn cellml:units="dimensionless">0.3</cn>
<apply>
<minus/>
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<apply>
<divide/>
<ci>ICaL</ci>
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<divide/>
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<apply>
<plus/>
<cn cellml:units="dimensionless">1</cn>
<apply>
<divide/>
<ci>Ca_ss</ci>
<cn cellml:units="mM">0.003</cn>
</apply>
</apply>
</apply>
<cn cellml:units="dimensionless">0.15</cn>
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</apply>
<apply>
<eq/>
<ci>fca2ss</ci>
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<divide/>
<cn cellml:units="dimensionless">1</cn>
<apply>
<minus/>
<cn cellml:units="dimensionless">1</cn>
<apply>
<divide/>
<ci>ICaL</ci>
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</apply>
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</apply>
<apply>
<eq/>
<ci>taufca</ci>
<apply>
<plus/>
<apply>
<divide/>
<apply>
<times/>
<cn cellml:units="ms">10</cn>
<ci>CaMKactive</ci>
</apply>
<apply>
<plus/>
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<ci>CaMKactive</ci>
</apply>
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<divide/>
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<apply>
<plus/>
<cn cellml:units="dimensionless">1</cn>
<apply>
<divide/>
<ci>Ca_ss</ci>
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</apply>
</apply>
</apply>
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</apply>
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<eq/>
<ci>taufca2</ci>
<apply>
<plus/>
<apply>
<divide/>
<cn cellml:units="ms">300</cn>
<apply>
<plus/>
<cn cellml:units="dimensionless">1</cn>
<apply>
<exp/>
<apply>
<divide/>
<apply>
<minus/>
<apply>
<minus/>
<ci>ICaL</ci>
</apply>
<cn cellml:units="uA_per_uF">0.175</cn>
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<cn cellml:units="uA_per_uF">0.04</cn>
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<eq/>
<apply>
<diff/>
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<ci>time</ci>
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<ci>d</ci>
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<divide/>
<apply>
<minus/>
<ci>dss</ci>
<ci>d</ci>
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<ci>taud</ci>
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<apply>
<eq/>
<apply>
<diff/>
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<ci>time</ci>
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<ci>dp</ci>
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<apply>
<divide/>
<apply>
<minus/>
<ci>dpss</ci>
<ci>dp</ci>
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<diff/>
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<divide/>
<apply>
<minus/>
<ci>fss</ci>
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<ci>tauf</ci>
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<eq/>
<apply>
<diff/>
<bvar>
<ci>time</ci>
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<ci>f2</ci>
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<apply>
<divide/>
<apply>
<minus/>
<ci>f2ss</ci>
<ci>f2</ci>
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<eq/>
<apply>
<diff/>
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<apply>
<divide/>
<apply>
<minus/>
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<ci>taufca</ci>
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<eq/>
<apply>
<diff/>
<bvar>
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<divide/>
<apply>
<minus/>
<ci>fca2ss</ci>
<ci>fca2</ci>
</apply>
<ci>taufca2</ci>
</apply>
</apply>
</math>
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<variable units="mV" public_interface="in" name="EK"/>
<variable units="mM" public_interface="in" name="K_o"/>
<variable units="per_ms" name="ak1"/>
<variable units="per_ms" name="bk1"/>
<variable units="uA_per_uF" public_interface="out" name="IK1"/>
<math xmlns="http://www.w3.org/1998/Math/MathML">
<apply>
<eq/>
<ci>ak1</ci>
<apply>
<divide/>
<cn cellml:units="per_ms">1.02</cn>
<apply>
<plus/>
<cn cellml:units="dimensionless">1</cn>
<apply>
<exp/>
<apply>
<times/>
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<minus/>
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<minus/>
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<eq/>
<ci>bk1</ci>
<apply>
<divide/>
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<plus/>
<apply>
<times/>
<cn cellml:units="per_ms">0.49124</cn>
<apply>
<exp/>
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<times/>
<cn cellml:units="per_mV">0.08032</cn>
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<plus/>
<apply>
<minus/>
<ci>V</ci>
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</apply>
<cn cellml:units="mV">5.476</cn>
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<apply>
<exp/>
<apply>
<times/>
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<minus/>
<apply>
<minus/>
<ci>V</ci>
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<plus/>
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<exp/>
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<times/>
<apply>
<minus/>
<cn cellml:units="per_mV">0.5143</cn>
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<plus/>
<apply>
<minus/>
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<eq/>
<ci>IK1</ci>
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<times/>
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<divide/>
<apply>
<times/>
<cn cellml:units="mS_per_uF">0.5</cn>
<apply>
<root/>
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<divide/>
<ci>K_o</ci>
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<ci>ak1</ci>
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<plus/>
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<apply>
<minus/>
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</math>
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<variable units="mV" public_interface="in" name="EK"/>
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<variable units="dimensionless" name="xrss"/>
<variable units="ms" name="tauxr"/>
<variable units="ms" public_interface="in" name="time"/>
<variable units="uA_per_uF" public_interface="out" name="IKr"/>
<math xmlns="http://www.w3.org/1998/Math/MathML">
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<eq/>
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<times/>
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<root/>
<apply>
<divide/>
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</apply>
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<eq/>
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<divide/>
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<plus/>
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<divide/>
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<plus/>
<ci>V</ci>
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<eq/>
<ci>IKr</ci>
<apply>
<times/>
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<ci>xr</ci>
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<apply>
<minus/>
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<eq/>
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<divide/>
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<plus/>
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<divide/>
<apply>
<minus/>
<apply>
<plus/>
<ci>V</ci>
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<eq/>
<ci>tauxr</ci>
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<divide/>
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<plus/>
<apply>
<divide/>
<apply>
<times/>
<cn cellml:units="per_mV">6e-4</cn>
<apply>
<minus/>
<ci>V</ci>
<cn cellml:units="mV">1.7384</cn>
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<apply>
<minus/>
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<times/>
<apply>
<minus/>
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<apply>
<minus/>
<ci>V</ci>
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</apply>
</apply>
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</apply>
<apply>
<divide/>
<apply>
<times/>
<cn cellml:units="per_mV">3e-4</cn>
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<plus/>
<ci>V</ci>
<cn cellml:units="mV">38.3608</cn>
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<apply>
<minus/>
<apply>
<exp/>
<apply>
<times/>
<cn cellml:units="per_mV">0.1522</cn>
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<plus/>
<ci>V</ci>
<cn cellml:units="mV">38.3608</cn>
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</apply>
</apply>
<cn cellml:units="dimensionless">1</cn>
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</apply>
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</apply>
<apply>
<eq/>
<apply>
<diff/>
<bvar>
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<ci>xr</ci>
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<apply>
<divide/>
<apply>
<minus/>
<ci>xrss</ci>
<ci>xr</ci>
</apply>
<ci>tauxr</ci>
</apply>
</apply>
</math>
</component>
<component name="IKs">
<variable units="mV" public_interface="in" name="V"/>
<variable units="mM" public_interface="in" name="Ca_i"/>
<variable units="ms" public_interface="in" name="time"/>
<variable units="mS_per_uF" name="gks"/>
<variable units="mV" public_interface="in" name="EKs"/>
<variable units="dimensionless" name="xss"/>
<variable units="ms" name="tauxs"/>
<variable units="dimensionless" name="xs1" initial_value="0.019883138161"/>
<variable units="dimensionless" name="xs2" initial_value="0.019890650554"/>
<variable units="uA_per_uF" public_interface="out" name="IKs"/>
<math xmlns="http://www.w3.org/1998/Math/MathML">
<apply>
<eq/>
<ci>gks</ci>
<apply>
<times/>
<cn cellml:units="mS_per_uF">0.0248975</cn>
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<plus/>
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<apply>
<divide/>
<cn cellml:units="dimensionless">0.6</cn>
<apply>
<plus/>
<cn cellml:units="dimensionless">1</cn>
<apply>
<power/>
<apply>
<divide/>
<cn cellml:units="mM">3.8e-5</cn>
<ci>Ca_i</ci>
</apply>
<cn cellml:units="dimensionless">1.4</cn>
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</apply>
</apply>
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</apply>
</apply>
<apply>
<eq/>
<ci>xss</ci>
<apply>
<divide/>
<cn cellml:units="dimensionless">1</cn>
<apply>
<plus/>
<cn cellml:units="dimensionless">1</cn>
<apply>
<exp/>
<apply>
<divide/>
<apply>
<minus/>
<apply>
<minus/>
<ci>V</ci>
<cn cellml:units="mV">10.5</cn>
</apply>
</apply>
<cn cellml:units="mV">24.7</cn>
</apply>
</apply>
</apply>
</apply>
</apply>
<apply>
<eq/>
<ci>tauxs</ci>
<apply>
<divide/>
<cn cellml:units="ms">1</cn>
<apply>
<plus/>
<apply>
<divide/>
<apply>
<times/>
<cn cellml:units="per_mV">7.61e-5</cn>
<apply>
<plus/>
<ci>V</ci>
<cn cellml:units="mV">44.6</cn>
</apply>
</apply>
<apply>
<minus/>
<cn cellml:units="dimensionless">1</cn>
<apply>
<exp/>
<apply>
<times/>
<apply>
<minus/>
<cn cellml:units="per_mV">9.97</cn>
</apply>
<apply>
<plus/>
<ci>V</ci>
<cn cellml:units="mV">44.6</cn>
</apply>
</apply>
</apply>
</apply>
</apply>
<apply>
<divide/>
<apply>
<times/>
<cn cellml:units="per_mV">3.6e-4</cn>
<apply>
<minus/>
<ci>V</ci>
<cn cellml:units="mV">0.55</cn>
</apply>
</apply>
<apply>
<minus/>
<apply>
<exp/>
<apply>
<times/>
<cn cellml:units="per_mV">0.128</cn>
<apply>
<minus/>
<ci>V</ci>
<cn cellml:units="mV">0.55</cn>
</apply>
</apply>
</apply>
<cn cellml:units="dimensionless">1</cn>
</apply>
</apply>
</apply>
</apply>
</apply>
<apply>
<eq/>
<ci>IKs</ci>
<apply>
<times/>
<ci>gks</ci>
<ci>xs1</ci>
<ci>xs2</ci>
<apply>
<minus/>
<ci>V</ci>
<ci>EKs</ci>
</apply>
</apply>
</apply>
<apply>
<eq/>
<apply>
<diff/>
<bvar>
<ci>time</ci>
</bvar>
<ci>xs1</ci>
</apply>
<apply>
<divide/>
<apply>
<minus/>
<ci>xss</ci>
<ci>xs1</ci>
</apply>
<ci>tauxs</ci>
</apply>
</apply>
<apply>
<eq/>
<apply>
<diff/>
<bvar>
<ci>time</ci>
</bvar>
<ci>xs2</ci>
</apply>
<apply>
<divide/>
<apply>
<divide/>
<apply>
<minus/>
<ci>xss</ci>
<ci>xs2</ci>
</apply>
<ci>tauxs</ci>
</apply>
<cn cellml:units="dimensionless">2</cn>
</apply>
</apply>
</math>
</component>
<component name="Ito">
<variable units="mV" public_interface="in" name="V"/>
<variable units="mS_per_uF" name="gitodv" initial_value="0.19"/>
<variable units="mV" public_interface="in" name="EK"/>
<variable units="dimensionless" name="rv"/>
<variable units="per_ms" name="ay"/>
<variable units="per_ms" name="by"/>
<variable units="per_ms" name="ay2"/>
<variable units="per_ms" name="by2"/>
<variable units="per_ms" name="ay3"/>
<variable units="per_ms" name="by3"/>
<variable units="ms" public_interface="in" name="time"/>
<variable units="dimensionless" name="ydv" initial_value="0.013970786703"/>
<variable units="dimensionless" name="ydv2" initial_value="0.99996472752"/>
<variable units="dimensionless" name="zdv" initial_value="0.829206149767"/>
<variable units="uA_per_uF" public_interface="out" name="Ito"/>
<math xmlns="http://www.w3.org/1998/Math/MathML">
<apply>
<eq/>
<ci>rv</ci>
<apply>
<exp/>
<apply>
<divide/>
<ci>V</ci>
<cn cellml:units="mV">300</cn>
</apply>
</apply>
</apply>
<apply>
<eq/>
<ci>ay</ci>
<apply>
<divide/>
<apply>
<times/>
<cn cellml:units="per_ms">25</cn>
<apply>
<exp/>
<apply>
<divide/>
<apply>
<minus/>
<ci>V</ci>
<cn cellml:units="mV">40</cn>
</apply>
<cn cellml:units="mV">25</cn>
</apply>
</apply>
</apply>
<apply>
<plus/>
<cn cellml:units="dimensionless">1</cn>
<apply>
<exp/>
<apply>
<divide/>
<apply>
<minus/>
<ci>V</ci>
<cn cellml:units="mV">40</cn>
</apply>
<cn cellml:units="mV">25</cn>
</apply>
</apply>
</apply>
</apply>
</apply>
<apply>
<eq/>
<ci>by</ci>
<apply>
<divide/>
<apply>
<times/>
<cn cellml:units="per_ms">25</cn>
<apply>
<exp/>
<apply>
<divide/>
<apply>
<minus/>
<apply>
<plus/>
<ci>V</ci>
<cn cellml:units="mV">90</cn>
</apply>
</apply>
<cn cellml:units="mV">25</cn>
</apply>
</apply>
</apply>
<apply>
<plus/>
<cn cellml:units="dimensionless">1</cn>
<apply>
<exp/>
<apply>
<divide/>
<apply>
<minus/>
<apply>
<plus/>
<ci>V</ci>
<cn cellml:units="mV">90</cn>
</apply>
</apply>
<cn cellml:units="mV">25</cn>
</apply>
</apply>
</apply>
</apply>
</apply>
<apply>
<eq/>
<ci>ay2</ci>
<apply>
<divide/>
<cn cellml:units="per_ms">0.03</cn>
<apply>
<plus/>
<cn cellml:units="dimensionless">1</cn>
<apply>
<exp/>
<apply>
<divide/>
<apply>
<plus/>
<ci>V</ci>
<cn cellml:units="mV">60</cn>
</apply>
<cn cellml:units="mV">5</cn>
</apply>
</apply>
</apply>
</apply>
</apply>
<apply>
<eq/>
<ci>by2</ci>
<apply>
<divide/>
<apply>
<times/>
<cn cellml:units="per_ms">0.2</cn>
<apply>
<exp/>
<apply>
<divide/>
<apply>
<plus/>
<ci>V</ci>
<cn cellml:units="mV">25</cn>
</apply>
<cn cellml:units="mV">5</cn>
</apply>
</apply>
</apply>
<apply>
<plus/>
<cn cellml:units="dimensionless">1</cn>
<apply>
<exp/>
<apply>
<divide/>
<apply>
<plus/>
<ci>V</ci>
<cn cellml:units="mV">25</cn>
</apply>
<cn cellml:units="mV">5</cn>
</apply>
</apply>
</apply>
</apply>
</apply>
<apply>
<eq/>
<ci>ay3</ci>
<apply>
<divide/>
<cn cellml:units="per_ms">0.00225</cn>
<apply>
<plus/>
<cn cellml:units="dimensionless">1</cn>
<apply>
<exp/>
<apply>
<divide/>
<apply>
<plus/>
<ci>V</ci>
<cn cellml:units="mV">60</cn>
</apply>
<cn cellml:units="mV">5</cn>
</apply>
</apply>
</apply>
</apply>
</apply>
<apply>
<eq/>
<ci>by3</ci>
<apply>
<divide/>
<apply>
<times/>
<cn cellml:units="per_ms">0.1</cn>
<apply>
<exp/>
<apply>
<divide/>
<apply>
<plus/>
<ci>V</ci>
<cn cellml:units="mV">25</cn>
</apply>
<cn cellml:units="mV">5</cn>
</apply>
</apply>
</apply>
<apply>
<plus/>
<cn cellml:units="dimensionless">1</cn>
<apply>
<exp/>
<apply>
<divide/>
<apply>
<plus/>
<ci>V</ci>
<cn cellml:units="mV">25</cn>
</apply>
<cn cellml:units="mV">5</cn>
</apply>
</apply>
</apply>
</apply>
</apply>
<apply>
<eq/>
<ci>Ito</ci>
<apply>
<times/>
<ci>gitodv</ci>
<apply>
<power/>
<ci>ydv</ci>
<cn cellml:units="dimensionless">3</cn>
</apply>
<ci>ydv2</ci>
<ci>zdv</ci>
<ci>rv</ci>
<apply>
<minus/>
<ci>V</ci>
<ci>EK</ci>
</apply>
</apply>
</apply>
<apply>
<eq/>
<apply>
<diff/>
<bvar>
<ci>time</ci>
</bvar>
<ci>ydv</ci>
</apply>
<apply>
<minus/>
<apply>
<times/>
<ci>ay</ci>
<apply>
<minus/>
<cn cellml:units="dimensionless">1</cn>
<ci>ydv</ci>
</apply>
</apply>
<apply>
<times/>
<ci>by</ci>
<ci>ydv</ci>
</apply>
</apply>
</apply>
<apply>
<eq/>
<apply>
<diff/>
<bvar>
<ci>time</ci>
</bvar>
<ci>ydv2</ci>
</apply>
<apply>
<minus/>
<apply>
<times/>
<ci>ay2</ci>
<apply>
<minus/>
<cn cellml:units="dimensionless">1</cn>
<ci>ydv2</ci>
</apply>
</apply>
<apply>
<times/>
<ci>by2</ci>
<ci>ydv2</ci>
</apply>
</apply>
</apply>
<apply>
<eq/>
<apply>
<diff/>
<bvar>
<ci>time</ci>
</bvar>
<ci>zdv</ci>
</apply>
<apply>
<minus/>
<apply>
<times/>
<ci>ay3</ci>
<apply>
<minus/>
<cn cellml:units="dimensionless">1</cn>
<ci>zdv</ci>
</apply>
</apply>
<apply>
<times/>
<ci>by3</ci>
<ci>zdv</ci>
</apply>
</apply>
</apply>
</math>
</component>
<component name="INaK">
<variable units="mV" public_interface="in" name="V"/>
<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="K_o"/>
<variable units="per_mV" public_interface="in" name="FonRT"/>
<variable units="mM" name="kmnai" initial_value="10"/>
<variable units="mM" name="kmko" initial_value="1.5"/>
<variable units="uA_per_uF" name="ibarnak" initial_value="0.61875"/>
<variable units="dimensionless" name="sigma"/>
<variable units="dimensionless" name="fnak"/>
<variable units="uA_per_uF" public_interface="out" name="INaK"/>
<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="mM">67.3</cn>
</apply>
</apply>
<cn cellml:units="dimensionless">1</cn>
</apply>
<cn cellml:units="dimensionless">7</cn>
</apply>
</apply>
<apply>
<eq/>
<ci>fnak</ci>
<apply>
<divide/>
<cn cellml:units="dimensionless">1</cn>
<apply>
<plus/>
<cn cellml:units="dimensionless">1</cn>
<apply>
<times/>
<cn cellml:units="dimensionless">0.1245</cn>
<apply>
<exp/>
<apply>
<times/>
<apply>
<minus/>
<cn cellml:units="dimensionless">0.1</cn>
</apply>
<ci>V</ci>
<ci>FonRT</ci>
</apply>
</apply>
</apply>
<apply>
<times/>
<cn cellml:units="dimensionless">0.0365</cn>
<ci>sigma</ci>
<apply>
<exp/>
<apply>
<times/>
<apply>
<minus/>
<ci>V</ci>
</apply>
<ci>FonRT</ci>
</apply>
</apply>
</apply>
</apply>
</apply>
</apply>
<apply>
<eq/>
<ci>INaK</ci>
<apply>
<divide/>
<apply>
<times/>
<apply>
<divide/>
<apply>
<times/>
<ci>ibarnak</ci>
<ci>fnak</ci>
<cn cellml:units="dimensionless">1</cn>
</apply>
<apply>
<plus/>
<cn cellml:units="dimensionless">1</cn>
<apply>
<power/>
<apply>
<divide/>
<ci>kmnai</ci>
<ci>Na_i</ci>
</apply>
<cn cellml:units="dimensionless">2</cn>
</apply>
</apply>
</apply>
<ci>K_o</ci>
</apply>
<apply>
<plus/>
<ci>K_o</ci>
<ci>kmko</ci>
</apply>
</apply>
</apply>
</math>
</component>
<component name="INaCa">
<variable units="mV" public_interface="in" name="V"/>
<variable units="per_mV" public_interface="in" name="FonRT"/>
<variable units="mM" public_interface="in" name="Ca_i"/>
<variable units="mM" public_interface="in" name="Ca_o"/>
<variable units="mM" public_interface="in" name="Na_i"/>
<variable units="mM" public_interface="in" name="Na_o"/>
<variable units="mM" name="ca_i_NaCa"/>
<variable units="mM" name="KmCa" initial_value="1.25e-4"/>
<variable units="dimensionless" name="allo"/>
<variable units="uA_per_uF" name="NCXmax" initial_value="4.5"/>
<variable units="dimensionless" name="ksat" initial_value="0.27"/>
<variable units="dimensionless" name="eta" initial_value="0.35"/>
<variable units="mM" name="KmNai" initial_value="12.3"/>
<variable units="mM" name="KmNao" initial_value="87.5"/>
<variable units="mM" name="KmCai" initial_value="0.0036"/>
<variable units="mM" name="KmCao" initial_value="1.3"/>
<variable units="mM4" name="num"/>
<variable units="dimensionless" name="denom1"/>
<variable units="mM4" name="denom2"/>
<variable units="mM4" name="denom3"/>
<variable units="uA_per_uF" public_interface="out" name="INaCa"/>
<math xmlns="http://www.w3.org/1998/Math/MathML">
<apply>
<eq/>
<ci>ca_i_NaCa</ci>
<apply>
<times/>
<cn cellml:units="dimensionless">1.5</cn>
<ci>Ca_i</ci>
</apply>
</apply>
<apply>
<eq/>
<ci>allo</ci>
<apply>
<divide/>
<cn cellml:units="dimensionless">1</cn>
<apply>
<plus/>
<cn cellml:units="dimensionless">1</cn>
<apply>
<power/>
<apply>
<divide/>
<ci>KmCa</ci>
<ci>ca_i_NaCa</ci>
</apply>
<cn cellml:units="dimensionless">2</cn>
</apply>
</apply>
</apply>
</apply>
<apply>
<eq/>
<ci>num</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/>
<ci>eta</ci>
<ci>V</ci>
<ci>FonRT</ci>
</apply>
</apply>
</apply>
<apply>
<times/>
<apply>
<power/>
<ci>Na_o</ci>
<cn cellml:units="dimensionless">3</cn>
</apply>
<ci>ca_i_NaCa</ci>
<apply>
<exp/>
<apply>
<times/>
<apply>
<minus/>
<ci>eta</ci>
<cn cellml:units="dimensionless">1</cn>
</apply>
<ci>V</ci>
<ci>FonRT</ci>
</apply>
</apply>
</apply>
</apply>
</apply>
<apply>
<eq/>
<ci>denom1</ci>
<apply>
<plus/>
<cn cellml:units="dimensionless">1</cn>
<apply>
<times/>
<ci>ksat</ci>
<apply>
<exp/>
<apply>
<times/>
<apply>
<minus/>
<ci>eta</ci>
<cn cellml:units="dimensionless">1</cn>
</apply>
<ci>V</ci>
<ci>FonRT</ci>
</apply>
</apply>
</apply>
</apply>
</apply>
<apply>
<eq/>
<ci>denom2</ci>
<apply>
<plus/>
<apply>
<times/>
<ci>KmCao</ci>
<apply>
<power/>
<ci>Na_i</ci>
<cn cellml:units="dimensionless">3</cn>
</apply>
</apply>
<apply>
<times/>
<apply>
<power/>
<ci>KmNao</ci>
<cn cellml:units="dimensionless">3</cn>
</apply>
<ci>ca_i_NaCa</ci>
</apply>
<apply>
<times/>
<apply>
<power/>
<ci>KmNai</ci>
<cn cellml:units="dimensionless">3</cn>
</apply>
<ci>Ca_o</ci>
<apply>
<plus/>
<cn cellml:units="dimensionless">1</cn>
<apply>
<divide/>
<ci>ca_i_NaCa</ci>
<ci>KmCai</ci>
</apply>
</apply>
</apply>
</apply>
</apply>
<apply>
<eq/>
<ci>denom3</ci>
<apply>
<plus/>
<apply>
<times/>
<ci>KmCai</ci>
<apply>
<power/>
<ci>Na_o</ci>
<cn cellml:units="dimensionless">3</cn>
</apply>
<apply>
<plus/>
<cn cellml:units="dimensionless">1</cn>
<apply>
<power/>
<apply>
<divide/>
<ci>Na_i</ci>
<ci>KmNai</ci>
</apply>
<cn cellml:units="dimensionless">3</cn>
</apply>
</apply>
</apply>
<apply>
<times/>
<apply>
<power/>
<ci>Na_i</ci>
<cn cellml:units="dimensionless">3</cn>
</apply>
<ci>Ca_o</ci>
</apply>
<apply>
<times/>
<apply>
<power/>
<ci>Na_o</ci>
<cn cellml:units="dimensionless">3</cn>
</apply>
<ci>ca_i_NaCa</ci>
</apply>
</apply>
</apply>
<apply>
<eq/>
<ci>INaCa</ci>
<apply>
<divide/>
<apply>
<times/>
<ci>NCXmax</ci>
<ci>allo</ci>
<ci>num</ci>
</apply>
<apply>
<times/>
<ci>denom1</ci>
<apply>
<plus/>
<ci>denom2</ci>
<ci>denom3</ci>
</apply>
</apply>
</apply>
</apply>
</math>
</component>
<component name="IKp">
<variable units="mV" public_interface="in" name="V"/>
<variable units="mV" public_interface="in" name="EK"/>
<variable units="uA_per_uF" public_interface="out" name="IKp"/>
<math xmlns="http://www.w3.org/1998/Math/MathML">
<apply>
<eq/>
<ci>IKp</ci>
<apply>
<divide/>
<apply>
<times/>
<cn cellml:units="mS_per_uF">0.00276</cn>
<apply>
<minus/>
<ci>V</ci>
<ci>EK</ci>
</apply>
</apply>
<apply>
<plus/>
<cn cellml:units="dimensionless">1</cn>
<apply>
<exp/>
<apply>
<divide/>
<apply>
<minus/>
<cn cellml:units="mV">7.488</cn>
<ci>V</ci>
</apply>
<cn cellml:units="mV">5.98</cn>
</apply>
</apply>
</apply>
</apply>
</apply>
</math>
</component>
<component name="IpCa">
<variable units="mM" public_interface="in" name="Ca_i"/>
<variable units="uA_per_uF" name="ibarpca" initial_value="0.0575"/>
<variable units="mM" name="kmpca" initial_value="0.5e-3"/>
<variable units="uA_per_uF" public_interface="out" name="IpCa"/>
<math xmlns="http://www.w3.org/1998/Math/MathML">
<apply>
<eq/>
<ci>IpCa</ci>
<apply>
<divide/>
<apply>
<times/>
<ci>ibarpca</ci>
<ci>Ca_i</ci>
</apply>
<apply>
<plus/>
<ci>kmpca</ci>
<ci>Ca_i</ci>
</apply>
</apply>
</apply>
</math>
</component>
<component name="ICab">
<variable units="mV" public_interface="in" name="V"/>
<variable units="C_per_mole" public_interface="in" name="F"/>
<variable units="per_mV" public_interface="in" name="FonRT"/>
<variable units="mM" public_interface="in" name="Ca_i"/>
<variable units="mM" public_interface="in" name="Ca_o"/>
<variable units="uA_per_uF" public_interface="out" name="ICab"/>
<math xmlns="http://www.w3.org/1998/Math/MathML">
<apply>
<eq/>
<ci>ICab</ci>
<apply>
<divide/>
<apply>
<times/>
<cn cellml:units="L_per_F_ms">1.995084e-7</cn>
<cn cellml:units="dimensionless">4</cn>
<ci>V</ci>
<ci>F</ci>
<ci>FonRT</ci>
<apply>
<minus/>
<apply>
<times/>
<ci>Ca_i</ci>
<apply>
<exp/>
<apply>
<times/>
<cn cellml:units="dimensionless">2</cn>
<ci>V</ci>
<ci>FonRT</ci>
</apply>
</apply>
</apply>
<apply>
<times/>
<cn cellml:units="dimensionless">0.341</cn>
<ci>Ca_o</ci>
</apply>
</apply>
</apply>
<apply>
<minus/>
<apply>
<exp/>
<apply>
<times/>
<cn cellml:units="dimensionless">2</cn>
<ci>V</ci>
<ci>FonRT</ci>
</apply>
</apply>
<cn cellml:units="dimensionless">1</cn>
</apply>
</apply>
</apply>
</math>
</component>
<component name="Ito2">
<variable units="ms" public_interface="in" name="time"/>
<variable units="mV" public_interface="in" name="V"/>
<variable units="C_per_mole" public_interface="in" name="F"/>
<variable units="per_mV" public_interface="in" name="FonRT"/>
<variable units="mM" public_interface="in" name="Cl_i"/>
<variable units="mM" public_interface="in" name="Cl_o"/>
<variable units="mM" public_interface="in" name="Ca_ss"/>
<variable units="L_per_F_ms" name="PCl" initial_value="4e-7"/>
<variable units="dimensionless" name="AA" initial_value="0.000816605172"/>
<variable units="uA_per_uF" name="Ito2_max"/>
<variable units="dimensionless" name="AAss"/>
<variable units="mM" name="Kmto2" initial_value="0.1502"/>
<variable units="uA_per_uF" public_interface="out" name="Ito2"/>
<math xmlns="http://www.w3.org/1998/Math/MathML">
<apply>
<eq/>
<ci>Ito2_max</ci>
<apply>
<divide/>
<apply>
<times/>
<ci>PCl</ci>
<ci>V</ci>
<ci>F</ci>
<ci>FonRT</ci>
<apply>
<minus/>
<ci>Cl_i</ci>
<apply>
<times/>
<ci>Cl_o</ci>
<apply>
<exp/>
<apply>
<times/>
<ci>V</ci>
<ci>FonRT</ci>
</apply>
</apply>
</apply>
</apply>
</apply>
<apply>
<minus/>
<cn cellml:units="dimensionless">1</cn>
<apply>
<exp/>
<apply>
<times/>
<ci>V</ci>
<ci>FonRT</ci>
</apply>
</apply>
</apply>
</apply>
</apply>
<apply>
<eq/>
<ci>AAss</ci>
<apply>
<divide/>
<cn cellml:units="dimensionless">1</cn>
<apply>
<plus/>
<cn cellml:units="dimensionless">1</cn>
<apply>
<divide/>
<ci>Kmto2</ci>
<ci>Ca_ss</ci>
</apply>
</apply>
</apply>
</apply>
<apply>
<eq/>
<ci>Ito2</ci>
<apply>
<times/>
<ci>Ito2_max</ci>
<ci>AA</ci>
</apply>
</apply>
<apply>
<eq/>
<apply>
<diff/>
<bvar>
<ci>time</ci>
</bvar>
<ci>AA</ci>
</apply>
<apply>
<divide/>
<apply>
<minus/>
<ci>AAss</ci>
<ci>AA</ci>
</apply>
<cn cellml:units="ms">1</cn>
</apply>
</apply>
</math>
</component>
<component name="IClb">
<variable units="mV" public_interface="in" name="V"/>
<variable units="mV" public_interface="in" name="ECl"/>
<variable units="mS_per_uF" name="GClb" initial_value="2.25e-4"/>
<variable units="uA_per_uF" public_interface="out" name="IClb"/>
<math xmlns="http://www.w3.org/1998/Math/MathML">
<apply>
<eq/>
<ci>IClb</ci>
<apply>
<times/>
<ci>GClb</ci>
<apply>
<minus/>
<ci>V</ci>
<ci>ECl</ci>
</apply>
</apply>
</apply>
</math>
</component>
<component name="INal">
<variable units="ms" public_interface="in" name="time"/>
<variable units="mV" public_interface="in" name="V"/>
<variable units="mV" public_interface="in" name="ENa"/>
<variable units="mS_per_uF" name="GNaL" initial_value="65e-4"/>
<variable units="dimensionless" name="mL" initial_value="0.001356538159"/>
<variable units="dimensionless" name="hL" initial_value="0.26130711759"/>
<variable units="per_ms" name="amL"/>
<variable units="per_ms" name="bmL"/>
<variable units="dimensionless" name="hLss"/>
<variable units="uA_per_uF" public_interface="out" name="INal"/>
<math xmlns="http://www.w3.org/1998/Math/MathML">
<apply>
<eq/>
<ci>INal</ci>
<apply>
<times/>
<ci>GNaL</ci>
<apply>
<power/>
<ci>mL</ci>
<cn cellml:units="dimensionless">3</cn>
</apply>
<ci>hL</ci>
<apply>
<minus/>
<ci>V</ci>
<ci>ENa</ci>
</apply>
</apply>
</apply>
<apply>
<eq/>
<ci>amL</ci>
<apply>
<divide/>
<apply>
<times/>
<cn cellml:units="per_ms">0.32</cn>
<cn cellml:units="per_mV">1</cn>
<apply>
<plus/>
<ci>V</ci>
<cn cellml:units="mV">47.13</cn>
</apply>
</apply>
<apply>
<minus/>
<cn cellml:units="dimensionless">1</cn>
<apply>
<exp/>
<apply>
<times/>
<apply>
<minus/>
<cn cellml:units="per_mV">0.1</cn>
</apply>
<apply>
<plus/>
<ci>V</ci>
<cn cellml:units="mV">47.13</cn>
</apply>
</apply>
</apply>
</apply>
</apply>
</apply>
<apply>
<eq/>
<ci>bmL</ci>
<apply>
<times/>
<cn cellml:units="per_ms">0.08</cn>
<apply>
<exp/>
<apply>
<divide/>
<apply>
<minus/>
<ci>V</ci>
</apply>
<cn cellml:units="mV">11</cn>
</apply>
</apply>
</apply>
</apply>
<apply>
<eq/>
<ci>hLss</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="mV">91</cn>
</apply>
<cn cellml:units="mV">6.1</cn>
</apply>
</apply>
</apply>
</apply>
</apply>
<apply>
<eq/>
<apply>
<diff/>
<bvar>
<ci>time</ci>
</bvar>
<ci>mL</ci>
</apply>
<apply>
<minus/>
<apply>
<times/>
<ci>amL</ci>
<apply>
<minus/>
<cn cellml:units="dimensionless">1</cn>
<ci>mL</ci>
</apply>
</apply>
<apply>
<times/>
<ci>bmL</ci>
<ci>mL</ci>
</apply>
</apply>
</apply>
<apply>
<eq/>
<apply>
<diff/>
<bvar>
<ci>time</ci>
</bvar>
<ci>hL</ci>
</apply>
<apply>
<divide/>
<apply>
<minus/>
<ci>hLss</ci>
<ci>hL</ci>
</apply>
<cn cellml:units="ms">600</cn>
</apply>
</apply>
</math>
</component>
<component name="reversal_potentials">
<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="K_o"/>
<variable units="mM" public_interface="in" name="K_i"/>
<variable units="mM" public_interface="in" name="Cl_o"/>
<variable units="mM" public_interface="in" name="Cl_i"/>
<variable units="per_mV" public_interface="in" name="FonRT"/>
<variable units="dimensionless" name="prnak" initial_value="0.01833"/>
<variable units="mV" public_interface="out" name="ENa"/>
<variable units="mV" public_interface="out" name="EK"/>
<variable units="mV" public_interface="out" name="EKs"/>
<variable units="mV" public_interface="out" name="ECl"/>
<math xmlns="http://www.w3.org/1998/Math/MathML">
<apply>
<eq/>
<ci>ENa</ci>
<apply>
<divide/>
<apply>
<ln/>
<apply>
<divide/>
<ci>Na_o</ci>
<ci>Na_i</ci>
</apply>
</apply>
<ci>FonRT</ci>
</apply>
</apply>
<apply>
<eq/>
<ci>EK</ci>
<apply>
<divide/>
<apply>
<ln/>
<apply>
<divide/>
<ci>K_o</ci>
<ci>K_i</ci>
</apply>
</apply>
<ci>FonRT</ci>
</apply>
</apply>
<apply>
<eq/>
<ci>EKs</ci>
<apply>
<divide/>
<apply>
<ln/>
<apply>
<divide/>
<apply>
<plus/>
<ci>K_o</ci>
<apply>
<times/>
<ci>prnak</ci>
<ci>Na_o</ci>
</apply>
</apply>
<apply>
<plus/>
<ci>K_i</ci>
<apply>
<times/>
<ci>prnak</ci>
<ci>Na_i</ci>
</apply>
</apply>
</apply>
</apply>
<ci>FonRT</ci>
</apply>
</apply>
<apply>
<eq/>
<ci>ECl</ci>
<apply>
<divide/>
<apply>
<minus/>
<apply>
<ln/>
<apply>
<divide/>
<ci>Cl_o</ci>
<ci>Cl_i</ci>
</apply>
</apply>
</apply>
<ci>FonRT</ci>
</apply>
</apply>
</math>
</component>
<component name="Irel">
<variable units="ms" public_interface="in" name="time"/>
<variable units="dimensionless" public_interface="in" name="tissue"/>
<variable units="mM" public_interface="in" name="Ca_ss"/>
<variable units="mM" public_interface="in" name="Ca_jsr"/>
<variable units="uA_per_uF" public_interface="in" name="ibarca"/>
<variable units="uA_per_uF" public_interface="in" name="ICaL"/>
<variable units="per_ms" name="Grel"/>
<variable units="dimensionless" name="dro_inf"/>
<variable units="ms" name="dtau_rel_max" initial_value="10"/>
<variable units="ms" name="dtau_rel"/>
<variable units="dimensionless" name="ross"/>
<variable units="dimensionless" name="riss"/>
<variable units="ms" name="tauri"/>
<variable units="mM_per_ms" public_interface="out" name="irelcicr"/>
<variable units="dimensionless" name="CaMK0" initial_value="0.05"/>
<variable units="mM" name="Km" initial_value="0.0015"/>
<variable units="dimensionless" public_interface="out" name="KmCaMK" initial_value="0.15"/>
<variable units="dimensionless" name="CaMKbound"/>
<variable units="dimensionless" public_interface="out" name="CaMKactive"/>
<variable units="dimensionless" name="CaMKtrap" initial_value="0.021123704774"/>
<variable units="dimensionless" name="ro" initial_value="0"/>
<variable units="dimensionless" name="ri" initial_value="0.862666650318"/>
<variable units="dimensionless" name="vg"/>
<variable units="dimensionless" name="cafac"/>
<math xmlns="http://www.w3.org/1998/Math/MathML">
<apply>
<eq/>
<ci>CaMKbound</ci>
<apply>
<divide/>
<apply>
<times/>
<ci>CaMK0</ci>
<apply>
<minus/>
<cn cellml:units="dimensionless">1</cn>
<ci>CaMKtrap</ci>
</apply>
</apply>
<apply>
<plus/>
<cn cellml:units="dimensionless">1</cn>
<apply>
<divide/>
<ci>Km</ci>
<ci>Ca_ss</ci>
</apply>
</apply>
</apply>
</apply>
<apply>
<eq/>
<ci>CaMKactive</ci>
<apply>
<plus/>
<ci>CaMKbound</ci>
<ci>CaMKtrap</ci>
</apply>
</apply>
<apply>
<eq/>
<ci>Grel</ci>
<apply>
<times/>
<cn cellml:units="per_ms">3000</cn>
<ci>vg</ci>
</apply>
</apply>
<apply>
<eq/>
<ci>vg</ci>
<piecewise>
<piece>
<apply>
<divide/>
<cn cellml:units="dimensionless">1</cn>
<apply>
<plus/>
<cn cellml:units="dimensionless">1</cn>
<apply>
<exp/>
<apply>
<divide/>
<apply>
<plus/>
<ci>ibarca</ci>
<cn cellml:units="uA_per_uF">13</cn>
</apply>
<cn cellml:units="uA_per_uF">5</cn>
</apply>
</apply>
</apply>
</apply>
<apply>
<eq/>
<ci>tissue</ci>
<cn cellml:units="dimensionless">0</cn>
</apply>
</piece>
<otherwise>
<cn cellml:units="dimensionless">1</cn>
</otherwise>
</piecewise>
</apply>
<apply>
<eq/>
<ci>cafac</ci>
<apply>
<divide/>
<cn cellml:units="dimensionless">1</cn>
<apply>
<plus/>
<cn cellml:units="dimensionless">1</cn>
<apply>
<exp/>
<apply>
<divide/>
<apply>
<plus/>
<ci>ICaL</ci>
<cn cellml:units="uA_per_uF">0.05</cn>
</apply>
<cn cellml:units="uA_per_uF">0.015</cn>
</apply>
</apply>
</apply>
</apply>
</apply>
<apply>
<eq/>
<ci>dro_inf</ci>
<apply>
<divide/>
<apply>
<power/>
<ci>Ca_jsr</ci>
<cn cellml:units="dimensionless">1.9</cn>
</apply>
<apply>
<plus/>
<apply>
<power/>
<ci>Ca_jsr</ci>
<cn cellml:units="dimensionless">1.9</cn>
</apply>
<apply>
<power/>
<apply>
<divide/>
<apply>
<times/>
<cn cellml:units="mM">49.28</cn>
<ci>Ca_ss</ci>
</apply>
<apply>
<plus/>
<ci>Ca_ss</ci>
<cn cellml:units="mM">0.0028</cn>
</apply>
</apply>
<cn cellml:units="dimensionless">1.9</cn>
</apply>
</apply>
</apply>
</apply>
<apply>
<eq/>
<ci>dtau_rel</ci>
<apply>
<divide/>
<apply>
<times/>
<ci>dtau_rel_max</ci>
<ci>CaMKactive</ci>
</apply>
<apply>
<plus/>
<ci>KmCaMK</ci>
<ci>CaMKactive</ci>
</apply>
</apply>
</apply>
<apply>
<eq/>
<ci>ross</ci>
<apply>
<divide/>
<ci>dro_inf</ci>
<apply>
<plus/>
<apply>
<power/>
<apply>
<divide/>
<cn cellml:units="uA_per_uF">1</cn>
<ci>ICaL</ci>
</apply>
<cn cellml:units="dimensionless">2</cn>
</apply>
<cn cellml:units="dimensionless">1</cn>
</apply>
</apply>
</apply>
<apply>
<eq/>
<ci>riss</ci>
<apply>
<divide/>
<cn cellml:units="dimensionless">1</cn>
<apply>
<plus/>
<cn cellml:units="dimensionless">1</cn>
<apply>
<exp/>
<apply>
<divide/>
<apply>
<plus/>
<apply>
<minus/>
<ci>Ca_ss</ci>
<cn cellml:units="mM">4e-4</cn>
</apply>
<apply>
<times/>
<cn cellml:units="mM">0.002</cn>
<ci>cafac</ci>
</apply>
</apply>
<cn cellml:units="mM">2.5e-5</cn>
</apply>
</apply>
</apply>
</apply>
</apply>
<apply>
<eq/>
<ci>tauri</ci>
<apply>
<plus/>
<cn cellml:units="ms">3</cn>
<ci>dtau_rel</ci>
<apply>
<divide/>
<apply>
<minus/>
<cn cellml:units="ms">350</cn>
<ci>dtau_rel</ci>
</apply>
<apply>
<plus/>
<cn cellml:units="dimensionless">1</cn>
<apply>
<exp/>
<apply>
<divide/>
<apply>
<plus/>
<apply>
<minus/>
<ci>Ca_ss</ci>
<cn cellml:units="mM">0.003</cn>
</apply>
<apply>
<times/>
<cn cellml:units="mM">0.003</cn>
<ci>cafac</ci>
</apply>
</apply>
<cn cellml:units="mM">2e-4</cn>
</apply>
</apply>
</apply>
</apply>
</apply>
</apply>
<apply>
<eq/>
<ci>irelcicr</ci>
<apply>
<times/>
<ci>Grel</ci>
<ci>ro</ci>
<ci>ri</ci>
<apply>
<minus/>
<ci>Ca_jsr</ci>
<ci>Ca_ss</ci>
</apply>
</apply>
</apply>
<apply>
<eq/>
<apply>
<diff/>
<bvar>
<ci>time</ci>
</bvar>
<ci>ro</ci>
</apply>
<apply>
<divide/>
<apply>
<minus/>
<ci>ross</ci>
<ci>ro</ci>
</apply>
<cn cellml:units="ms">3</cn>
</apply>
</apply>
<apply>
<eq/>
<apply>
<diff/>
<bvar>
<ci>time</ci>
</bvar>
<ci>ri</ci>
</apply>
<apply>
<divide/>
<apply>
<minus/>
<ci>riss</ci>
<ci>ri</ci>
</apply>
<ci>tauri</ci>
</apply>
</apply>
<apply>
<eq/>
<apply>
<diff/>
<bvar>
<ci>time</ci>
</bvar>
<ci>CaMKtrap</ci>
</apply>
<apply>
<minus/>
<apply>
<times/>
<cn cellml:units="per_ms">0.05</cn>
<ci>CaMKactive</ci>
<apply>
<minus/>
<ci>CaMKactive</ci>
<ci>CaMKtrap</ci>
</apply>
</apply>
<apply>
<times/>
<cn cellml:units="per_ms">6.8e-4</cn>
<ci>CaMKtrap</ci>
</apply>
</apply>
</apply>
</math>
</component>
<component name="Iup_Ileak">
<variable units="mM" name="dKmPLBmax" initial_value="0.00017"/>
<variable units="dimensionless" name="dJupmax" initial_value="0.75"/>
<variable units="mM" name="dKmPLB"/>
<variable units="dimensionless" name="dJup"/>
<variable units="mM_per_ms" name="iupmax" initial_value="0.004375"/>
<variable units="mM" name="Kmup" initial_value="0.00092"/>
<variable units="mM" name="nsrmax" initial_value="15"/>
<variable units="mM_per_ms" public_interface="out" name="iup"/>
<variable units="mM_per_ms" public_interface="out" name="ileak"/>
<variable units="dimensionless" public_interface="in" name="KmCaMK"/>
<variable units="dimensionless" public_interface="in" name="CaMKactive"/>
<variable units="mM" public_interface="in" name="Ca_i"/>
<variable units="mM" public_interface="in" name="Ca_nsr"/>
<math xmlns="http://www.w3.org/1998/Math/MathML">
<apply>
<eq/>
<ci>dKmPLB</ci>
<apply>
<divide/>
<apply>
<times/>
<ci>dKmPLBmax</ci>
<ci>CaMKactive</ci>
</apply>
<apply>
<plus/>
<ci>KmCaMK</ci>
<ci>CaMKactive</ci>
</apply>
</apply>
</apply>
<apply>
<eq/>
<ci>dJup</ci>
<apply>
<divide/>
<apply>
<times/>
<ci>dJupmax</ci>
<ci>CaMKactive</ci>
</apply>
<apply>
<plus/>
<ci>KmCaMK</ci>
<ci>CaMKactive</ci>
</apply>
</apply>
</apply>
<apply>
<eq/>
<ci>iup</ci>
<apply>
<divide/>
<apply>
<times/>
<apply>
<plus/>
<ci>dJup</ci>
<cn cellml:units="dimensionless">1</cn>
</apply>
<ci>iupmax</ci>
<ci>Ca_i</ci>
</apply>
<apply>
<minus/>
<apply>
<plus/>
<ci>Ca_i</ci>
<ci>Kmup</ci>
</apply>
<ci>dKmPLB</ci>
</apply>
</apply>
</apply>
<apply>
<eq/>
<ci>ileak</ci>
<apply>
<divide/>
<apply>
<times/>
<ci>iupmax</ci>
<ci>Ca_nsr</ci>
</apply>
<ci>nsrmax</ci>
</apply>
</apply>
</math>
</component>
<component name="Idiff_Itr">
<variable units="mM_per_ms" public_interface="out" name="idiff"/>
<variable units="mM_per_ms" public_interface="out" name="itr"/>
<variable units="mM" public_interface="in" name="Ca_ss"/>
<variable units="mM" public_interface="in" name="Ca_i"/>
<variable units="mM" public_interface="in" name="Ca_nsr"/>
<variable units="mM" public_interface="in" name="Ca_jsr"/>
<math xmlns="http://www.w3.org/1998/Math/MathML">
<apply>
<eq/>
<ci>idiff</ci>
<apply>
<divide/>
<apply>
<minus/>
<ci>Ca_ss</ci>
<ci>Ca_i</ci>
</apply>
<cn cellml:units="ms">0.2</cn>
</apply>
</apply>
<apply>
<eq/>
<ci>itr</ci>
<apply>
<divide/>
<apply>
<minus/>
<ci>Ca_nsr</ci>
<ci>Ca_jsr</ci>
</apply>
<cn cellml:units="ms">120</cn>
</apply>
</apply>
</math>
</component>
<component name="Na">
<variable units="ms" public_interface="in" name="time"/>
<variable units="mM" public_interface="out" name="Na_i" initial_value="12.972433387269"/>
<variable units="uA_per_uF" public_interface="in" name="naiont"/>
<variable units="uF_mole_per_C" public_interface="in" name="AF"/>
<variable units="uL" public_interface="in" name="vmyo"/>
<variable units="mM_per_ms" public_interface="out" name="CTNaCl"/>
<variable units="mM_per_ms" name="CTNaClmax" initial_value="9.8443e-6"/>
<variable units="mV" public_interface="in" name="ENa"/>
<variable units="mV" public_interface="in" name="ECl"/>
<math xmlns="http://www.w3.org/1998/Math/MathML">
<apply>
<eq/>
<ci>CTNaCl</ci>
<apply>
<divide/>
<apply>
<times/>
<ci>CTNaClmax</ci>
<apply>
<power/>
<apply>
<minus/>
<ci>ENa</ci>
<ci>ECl</ci>
</apply>
<cn cellml:units="dimensionless">4</cn>
</apply>
</apply>
<apply>
<plus/>
<apply>
<power/>
<apply>
<minus/>
<ci>ENa</ci>
<ci>ECl</ci>
</apply>
<cn cellml:units="dimensionless">4</cn>
</apply>
<apply>
<power/>
<cn cellml:units="mV">87.8251</cn>
<cn cellml:units="dimensionless">4</cn>
</apply>
</apply>
</apply>
</apply>
<apply>
<eq/>
<apply>
<diff/>
<bvar>
<ci>time</ci>
</bvar>
<ci>Na_i</ci>
</apply>
<apply>
<plus/>
<apply>
<divide/>
<apply>
<times/>
<apply>
<minus/>
<ci>naiont</ci>
</apply>
<ci>AF</ci>
</apply>
<ci>vmyo</ci>
</apply>
<ci>CTNaCl</ci>
</apply>
</apply>
</math>
</component>
<component name="K">
<variable units="ms" public_interface="in" name="time"/>
<variable units="mM" public_interface="out" name="K_i" initial_value="135.469546216758"/>
<variable units="uA_per_uF" public_interface="in" name="kiont"/>
<variable units="uF_mole_per_C" public_interface="in" name="AF"/>
<variable units="uL" public_interface="in" name="vmyo"/>
<variable units="mM_per_ms" public_interface="out" name="CTKCl"/>
<variable units="mM_per_ms" name="CTKClmax" initial_value="7.0756e-6"/>
<variable units="mV" public_interface="in" name="EK"/>
<variable units="mV" public_interface="in" name="ECl"/>
<math xmlns="http://www.w3.org/1998/Math/MathML">
<apply>
<eq/>
<ci>CTKCl</ci>
<apply>
<divide/>
<apply>
<times/>
<ci>CTKClmax</ci>
<apply>
<minus/>
<ci>EK</ci>
<ci>ECl</ci>
</apply>
</apply>
<apply>
<plus/>
<apply>
<minus/>
<ci>EK</ci>
<ci>ECl</ci>
</apply>
<cn cellml:units="mV">87.8251</cn>
</apply>
</apply>
</apply>
<apply>
<eq/>
<apply>
<diff/>
<bvar>
<ci>time</ci>
</bvar>
<ci>K_i</ci>
</apply>
<apply>
<plus/>
<apply>
<divide/>
<apply>
<times/>
<apply>
<minus/>
<ci>kiont</ci>
</apply>
<ci>AF</ci>
</apply>
<ci>vmyo</ci>
</apply>
<ci>CTKCl</ci>
</apply>
</apply>
</math>
</component>
<component name="Cl">
<variable units="ms" public_interface="in" name="time"/>
<variable units="mM" public_interface="out" name="Cl_i" initial_value="15.59207157178"/>
<variable units="uA_per_uF" public_interface="in" name="clont"/>
<variable units="uF_mole_per_C" public_interface="in" name="AF"/>
<variable units="uL" public_interface="in" name="vmyo"/>
<variable units="mM_per_ms" public_interface="in" name="CTNaCl"/>
<variable units="mM_per_ms" public_interface="in" name="CTKCl"/>
<math xmlns="http://www.w3.org/1998/Math/MathML">
<apply>
<eq/>
<apply>
<diff/>
<bvar>
<ci>time</ci>
</bvar>
<ci>Cl_i</ci>
</apply>
<apply>
<plus/>
<apply>
<divide/>
<apply>
<times/>
<ci>clont</ci>
<ci>AF</ci>
</apply>
<ci>vmyo</ci>
</apply>
<ci>CTNaCl</ci>
<ci>CTKCl</ci>
</apply>
</apply>
</math>
</component>
<component name="Ca">
<variable units="ms" public_interface="in" name="time"/>
<variable units="mM" public_interface="out" name="Ca_i" initial_value="0.00012131666"/>
<variable units="mM" public_interface="out" name="Ca_jsr" initial_value="1.737580994071"/>
<variable units="mM" public_interface="out" name="Ca_nsr" initial_value="1.832822335168"/>
<variable units="mM" public_interface="out" name="Ca_ss" initial_value="0.00012271265"/>
<variable units="mM" name="kmt" initial_value="0.5e-3"/>
<variable units="mM" name="kmc" initial_value="2.38e-3"/>
<variable units="mM" name="tbar" initial_value="70e-3"/>
<variable units="mM" name="cbar" initial_value="50e-3"/>
<variable units="mM" name="kmcsqn" initial_value="0.8"/>
<variable units="mM" name="csqnbar" initial_value="10"/>
<variable units="dimensionless" name="bcsqn"/>
<variable units="dimensionless" name="bmyo"/>
<variable units="mM" name="BSRmax" initial_value="0.047"/>
<variable units="mM" name="KmBSR" initial_value="0.00087"/>
<variable units="mM" name="BSLmax" initial_value="1.124"/>
<variable units="mM" name="KmBSL" initial_value="0.0087"/>
<variable units="dimensionless" name="bss"/>
<variable units="uA_per_uF" public_interface="in" name="ICab"/>
<variable units="uA_per_uF" public_interface="in" name="ICaL"/>
<variable units="uA_per_uF" public_interface="in" name="IpCa"/>
<variable units="uA_per_uF" public_interface="in" name="INaCa"/>
<variable units="uL" public_interface="in" name="vmyo"/>
<variable units="uL" public_interface="in" name="vsr"/>
<variable units="uL" public_interface="in" name="vnsr"/>
<variable units="uL" public_interface="in" name="vjsr"/>
<variable units="uL" public_interface="in" name="vss"/>
<variable units="uF_mole_per_C" public_interface="in" name="AF"/>
<variable units="mM_per_ms" public_interface="in" name="iup"/>
<variable units="mM_per_ms" public_interface="in" name="ileak"/>
<variable units="mM_per_ms" public_interface="in" name="irelcicr"/>
<variable units="mM_per_ms" public_interface="in" name="idiff"/>
<variable units="mM_per_ms" public_interface="in" name="itr"/>
<math xmlns="http://www.w3.org/1998/Math/MathML">
<apply>
<eq/>
<apply>
<diff/>
<bvar>
<ci>time</ci>
</bvar>
<ci>Ca_i</ci>
</apply>
<apply>
<times/>
<ci>bmyo</ci>
<apply>
<plus/>
<apply>
<divide/>
<apply>
<times/>
<apply>
<minus/>
<apply>
<minus/>
<apply>
<plus/>
<ci>ICab</ci>
<ci>IpCa</ci>
</apply>
<apply>
<times/>
<cn cellml:units="dimensionless">2</cn>
<ci>INaCa</ci>
</apply>
</apply>
</apply>
<ci>AF</ci>
</apply>
<apply>
<times/>
<ci>vmyo</ci>
<cn cellml:units="dimensionless">2</cn>
</apply>
</apply>
<apply>
<divide/>
<apply>
<times/>
<apply>
<minus/>
<ci>ileak</ci>
<ci>iup</ci>
</apply>
<ci>vnsr</ci>
</apply>
<ci>vmyo</ci>
</apply>
<apply>
<divide/>
<apply>
<times/>
<ci>idiff</ci>
<ci>vss</ci>
</apply>
<ci>vmyo</ci>
</apply>
</apply>
</apply>
</apply>
<apply>
<eq/>
<apply>
<diff/>
<bvar>
<ci>time</ci>
</bvar>
<ci>Ca_ss</ci>
</apply>
<apply>
<times/>
<ci>bss</ci>
<apply>
<minus/>
<apply>
<plus/>
<apply>
<divide/>
<apply>
<times/>
<apply>
<minus/>
<ci>ICaL</ci>
</apply>
<ci>AF</ci>
</apply>
<apply>
<times/>
<ci>vss</ci>
<cn cellml:units="dimensionless">2</cn>
</apply>
</apply>
<apply>
<divide/>
<apply>
<times/>
<ci>irelcicr</ci>
<ci>vjsr</ci>
</apply>
<ci>vss</ci>
</apply>
</apply>
<ci>idiff</ci>
</apply>
</apply>
</apply>
<apply>
<eq/>
<apply>
<diff/>
<bvar>
<ci>time</ci>
</bvar>
<ci>Ca_nsr</ci>
</apply>
<apply>
<minus/>
<apply>
<minus/>
<ci>iup</ci>
<apply>
<divide/>
<apply>
<times/>
<ci>itr</ci>
<ci>vjsr</ci>
</apply>
<ci>vnsr</ci>
</apply>
</apply>
<ci>ileak</ci>
</apply>
</apply>
<apply>
<eq/>
<apply>
<diff/>
<bvar>
<ci>time</ci>
</bvar>
<ci>Ca_jsr</ci>
</apply>
<apply>
<times/>
<ci>bcsqn</ci>
<apply>
<minus/>
<ci>itr</ci>
<ci>irelcicr</ci>
</apply>
</apply>
</apply>
<apply>
<eq/>
<ci>bcsqn</ci>
<apply>
<divide/>
<cn cellml:units="dimensionless">1</cn>
<apply>
<plus/>
<cn cellml:units="dimensionless">1</cn>
<apply>
<divide/>
<apply>
<times/>
<ci>kmcsqn</ci>
<ci>csqnbar</ci>
</apply>
<apply>
<power/>
<apply>
<plus/>
<ci>Ca_jsr</ci>
<ci>kmcsqn</ci>
</apply>
<cn cellml:units="dimensionless">2</cn>
</apply>
</apply>
</apply>
</apply>
</apply>
<apply>
<eq/>
<ci>bmyo</ci>
<apply>
<divide/>
<cn cellml:units="dimensionless">1</cn>
<apply>
<plus/>
<cn cellml:units="dimensionless">1</cn>
<apply>
<divide/>
<apply>
<times/>
<ci>cbar</ci>
<ci>kmc</ci>
</apply>
<apply>
<power/>
<apply>
<plus/>
<ci>Ca_i</ci>
<ci>kmc</ci>
</apply>
<cn cellml:units="dimensionless">2</cn>
</apply>
</apply>
<apply>
<divide/>
<apply>
<times/>
<ci>kmt</ci>
<ci>tbar</ci>
</apply>
<apply>
<power/>
<apply>
<plus/>
<ci>Ca_i</ci>
<ci>kmt</ci>
</apply>
<cn cellml:units="dimensionless">2</cn>
</apply>
</apply>
</apply>
</apply>
</apply>
<apply>
<eq/>
<ci>bss</ci>
<apply>
<divide/>
<cn cellml:units="dimensionless">1</cn>
<apply>
<plus/>
<cn cellml:units="dimensionless">1</cn>
<apply>
<divide/>
<apply>
<times/>
<ci>BSRmax</ci>
<ci>KmBSR</ci>
</apply>
<apply>
<power/>
<apply>
<plus/>
<ci>KmBSR</ci>
<ci>Ca_ss</ci>
</apply>
<cn cellml:units="dimensionless">2</cn>
</apply>
</apply>
<apply>
<divide/>
<apply>
<times/>
<ci>BSLmax</ci>
<ci>KmBSL</ci>
</apply>
<apply>
<power/>
<apply>
<plus/>
<ci>KmBSL</ci>
<ci>Ca_ss</ci>
</apply>
<cn cellml:units="dimensionless">2</cn>
</apply>
</apply>
</apply>
</apply>
</apply>
</math>
</component>
<component name="intracellular_currents"/>
<component name="transmembrane_currents"/>
<component name="Ions_n_reversal_potentials"/>
<group>
<relationship_ref relationship="containment"/>
<component_ref component="cell">
<component_ref component="transmembrane_currents">
<component_ref component="INa"/>
<component_ref component="ICaL"/>
<component_ref component="IK1"/>
<component_ref component="IKr"/>
<component_ref component="IKs"/>
<component_ref component="Ito"/>
<component_ref component="INaK"/>
<component_ref component="INaCa"/>
<component_ref component="IKp"/>
<component_ref component="IpCa"/>
<component_ref component="ICab"/>
<component_ref component="Ito2"/>
<component_ref component="IClb"/>
<component_ref component="INal"/>
</component_ref>
<component_ref component="intracellular_currents">
<component_ref component="Irel"/>
<component_ref component="Iup_Ileak"/>
<component_ref component="Idiff_Itr"/>
</component_ref>
<component_ref component="Ions_n_reversal_potentials">
<component_ref component="Ca"/>
<component_ref component="Na"/>
<component_ref component="K"/>
<component_ref component="Cl"/>
<component_ref component="reversal_potentials"/>
</component_ref>
</component_ref>
</group>
<connection>
<map_components component_2="Environment" component_1="cell"/>
<map_variables variable_2="time" variable_1="time"/>
<map_variables variable_2="F" variable_1="F"/>
</connection>
<connection>
<map_components component_2="Environment" component_1="reversal_potentials"/>
<map_variables variable_2="K_o" variable_1="K_o"/>
<map_variables variable_2="Na_o" variable_1="Na_o"/>
<map_variables variable_2="Cl_o" variable_1="Cl_o"/>
<map_variables variable_2="FonRT" variable_1="FonRT"/>
</connection>
<connection>
<map_components component_2="Environment" component_1="INa"/>
<map_variables variable_2="time" variable_1="time"/>
<map_variables variable_2="tissue" variable_1="tissue"/>
</connection>
<connection>
<map_components component_2="Environment" component_1="ICaL"/>
<map_variables variable_2="time" variable_1="time"/>
<map_variables variable_2="Ca_o" variable_1="Ca_o"/>
<map_variables variable_2="F" variable_1="F"/>
<map_variables variable_2="FonRT" variable_1="FonRT"/>
<map_variables variable_2="tissue" variable_1="tissue"/>
</connection>
<connection>
<map_components component_2="Environment" component_1="IKr"/>
<map_variables variable_2="time" variable_1="time"/>
<map_variables variable_2="K_o" variable_1="K_o"/>
</connection>
<connection>
<map_components component_2="Environment" component_1="IKs"/>
<map_variables variable_2="time" variable_1="time"/>
</connection>
<connection>
<map_components component_2="Environment" component_1="IK1"/>
<map_variables variable_2="K_o" variable_1="K_o"/>
</connection>
<connection>
<map_components component_2="Environment" component_1="Ito"/>
<map_variables variable_2="time" variable_1="time"/>
</connection>
<connection>
<map_components component_2="Environment" component_1="INaK"/>
<map_variables variable_2="K_o" variable_1="K_o"/>
<map_variables variable_2="Na_o" variable_1="Na_o"/>
<map_variables variable_2="FonRT" variable_1="FonRT"/>
</connection>
<connection>
<map_components component_2="Environment" component_1="INaCa"/>
<map_variables variable_2="Ca_o" variable_1="Ca_o"/>
<map_variables variable_2="Na_o" variable_1="Na_o"/>
<map_variables variable_2="FonRT" variable_1="FonRT"/>
</connection>
<connection>
<map_components component_2="Environment" component_1="ICab"/>
<map_variables variable_2="F" variable_1="F"/>
<map_variables variable_2="FonRT" variable_1="FonRT"/>
<map_variables variable_2="Ca_o" variable_1="Ca_o"/>
</connection>
<connection>
<map_components component_2="Environment" component_1="Ito2"/>
<map_variables variable_2="time" variable_1="time"/>
<map_variables variable_2="F" variable_1="F"/>
<map_variables variable_2="FonRT" variable_1="FonRT"/>
<map_variables variable_2="Cl_o" variable_1="Cl_o"/>
</connection>
<connection>
<map_components component_2="Environment" component_1="INal"/>
<map_variables variable_2="time" variable_1="time"/>
</connection>
<connection>
<map_components component_2="Environment" component_1="Irel"/>
<map_variables variable_2="time" variable_1="time"/>
<map_variables variable_2="tissue" variable_1="tissue"/>
</connection>
<connection>
<map_components component_2="Environment" component_1="Ca"/>
<map_variables variable_2="time" variable_1="time"/>
</connection>
<connection>
<map_components component_2="Environment" component_1="Na"/>
<map_variables variable_2="time" variable_1="time"/>
</connection>
<connection>
<map_components component_2="Environment" component_1="K"/>
<map_variables variable_2="time" variable_1="time"/>
</connection>
<connection>
<map_components component_2="Environment" component_1="Cl"/>
<map_variables variable_2="time" variable_1="time"/>
</connection>
<connection>
<map_components component_2="INa" component_1="cell"/>
<map_variables variable_2="V" variable_1="V"/>
<map_variables variable_2="INa" variable_1="INa"/>
</connection>
<connection>
<map_components component_2="ICaL" component_1="cell"/>
<map_variables variable_2="V" variable_1="V"/>
<map_variables variable_2="ICaL" variable_1="ICaL"/>
</connection>
<connection>
<map_components component_2="IpCa" component_1="cell"/>
<map_variables variable_2="IpCa" variable_1="IpCa"/>
</connection>
<connection>
<map_components component_2="ICab" component_1="cell"/>
<map_variables variable_2="V" variable_1="V"/>
<map_variables variable_2="ICab" variable_1="ICab"/>
</connection>
<connection>
<map_components component_2="IKr" component_1="cell"/>
<map_variables variable_2="V" variable_1="V"/>
<map_variables variable_2="IKr" variable_1="IKr"/>
</connection>
<connection>
<map_components component_2="IKs" component_1="cell"/>
<map_variables variable_2="V" variable_1="V"/>
<map_variables variable_2="IKs" variable_1="IKs"/>
</connection>
<connection>
<map_components component_2="IKp" component_1="cell"/>
<map_variables variable_2="V" variable_1="V"/>
<map_variables variable_2="IKp" variable_1="IKp"/>
</connection>
<connection>
<map_components component_2="Ito" component_1="cell"/>
<map_variables variable_2="V" variable_1="V"/>
<map_variables variable_2="Ito" variable_1="Ito"/>
</connection>
<connection>
<map_components component_2="IK1" component_1="cell"/>
<map_variables variable_2="V" variable_1="V"/>
<map_variables variable_2="IK1" variable_1="IK1"/>
</connection>
<connection>
<map_components component_2="INaK" component_1="cell"/>
<map_variables variable_2="V" variable_1="V"/>
<map_variables variable_2="INaK" variable_1="INaK"/>
</connection>
<connection>
<map_components component_2="INaCa" component_1="cell"/>
<map_variables variable_2="V" variable_1="V"/>
<map_variables variable_2="INaCa" variable_1="INaCa"/>
</connection>
<connection>
<map_components component_2="Ito2" component_1="cell"/>
<map_variables variable_2="V" variable_1="V"/>
<map_variables variable_2="Ito2" variable_1="Ito2"/>
</connection>
<connection>
<map_components component_2="IClb" component_1="cell"/>
<map_variables variable_2="V" variable_1="V"/>
<map_variables variable_2="IClb" variable_1="IClb"/>
</connection>
<connection>
<map_components component_2="INal" component_1="cell"/>
<map_variables variable_2="V" variable_1="V"/>
<map_variables variable_2="INal" variable_1="INal"/>
</connection>
<connection>
<map_components component_2="Na" component_1="cell"/>
<map_variables variable_2="naiont" variable_1="naiont"/>
<map_variables variable_2="AF" variable_1="AF"/>
<map_variables variable_2="vmyo" variable_1="vmyo"/>
</connection>
<connection>
<map_components component_2="K" component_1="cell"/>
<map_variables variable_2="kiont" variable_1="kiont"/>
<map_variables variable_2="AF" variable_1="AF"/>
<map_variables variable_2="vmyo" variable_1="vmyo"/>
</connection>
<connection>
<map_components component_2="Cl" component_1="cell"/>
<map_variables variable_2="clont" variable_1="clont"/>
<map_variables variable_2="AF" variable_1="AF"/>
<map_variables variable_2="vmyo" variable_1="vmyo"/>
</connection>
<connection>
<map_components component_2="Ca" component_1="cell"/>
<map_variables variable_2="AF" variable_1="AF"/>
<map_variables variable_2="vmyo" variable_1="vmyo"/>
<map_variables variable_2="vss" variable_1="vss"/>
<map_variables variable_2="vsr" variable_1="vsr"/>
<map_variables variable_2="vjsr" variable_1="vjsr"/>
<map_variables variable_2="vnsr" variable_1="vnsr"/>
</connection>
<connection>
<map_components component_2="IK1" component_1="reversal_potentials"/>
<map_variables variable_2="EK" variable_1="EK"/>
</connection>
<connection>
<map_components component_2="IKr" component_1="reversal_potentials"/>
<map_variables variable_2="EK" variable_1="EK"/>
</connection>
<connection>
<map_components component_2="Ito" component_1="reversal_potentials"/>
<map_variables variable_2="EK" variable_1="EK"/>
</connection>
<connection>
<map_components component_2="IKp" component_1="reversal_potentials"/>
<map_variables variable_2="EK" variable_1="EK"/>
</connection>
<connection>
<map_components component_2="IKs" component_1="reversal_potentials"/>
<map_variables variable_2="EKs" variable_1="EKs"/>
</connection>
<connection>
<map_components component_2="INa" component_1="reversal_potentials"/>
<map_variables variable_2="ENa" variable_1="ENa"/>
</connection>
<connection>
<map_components component_2="IClb" component_1="reversal_potentials"/>
<map_variables variable_2="ECl" variable_1="ECl"/>
</connection>
<connection>
<map_components component_2="INal" component_1="reversal_potentials"/>
<map_variables variable_2="ENa" variable_1="ENa"/>
</connection>
<connection>
<map_components component_2="Na" component_1="reversal_potentials"/>
<map_variables variable_2="ENa" variable_1="ENa"/>
<map_variables variable_2="ECl" variable_1="ECl"/>
<map_variables variable_2="Na_i" variable_1="Na_i"/>
</connection>
<connection>
<map_components component_2="K" component_1="reversal_potentials"/>
<map_variables variable_2="EK" variable_1="EK"/>
<map_variables variable_2="ECl" variable_1="ECl"/>
<map_variables variable_2="K_i" variable_1="K_i"/>
</connection>
<connection>
<map_components component_2="Cl" component_1="reversal_potentials"/>
<map_variables variable_2="Cl_i" variable_1="Cl_i"/>
</connection>
<connection>
<map_components component_2="Na" component_1="INaK"/>
<map_variables variable_2="Na_i" variable_1="Na_i"/>
</connection>
<connection>
<map_components component_2="Na" component_1="INaCa"/>
<map_variables variable_2="Na_i" variable_1="Na_i"/>
</connection>
<connection>
<map_components component_2="Ca" component_1="INaCa"/>
<map_variables variable_2="INaCa" variable_1="INaCa"/>
<map_variables variable_2="Ca_i" variable_1="Ca_i"/>
</connection>
<connection>
<map_components component_2="Ca" component_1="IpCa"/>
<map_variables variable_2="IpCa" variable_1="IpCa"/>
<map_variables variable_2="Ca_i" variable_1="Ca_i"/>
</connection>
<connection>
<map_components component_2="Ca" component_1="ICab"/>
<map_variables variable_2="ICab" variable_1="ICab"/>
<map_variables variable_2="Ca_i" variable_1="Ca_i"/>
</connection>
<connection>
<map_components component_2="Ca" component_1="ICaL"/>
<map_variables variable_2="Ca_ss" variable_1="Ca_ss"/>
<map_variables variable_2="ICaL" variable_1="ICaL"/>
</connection>
<connection>
<map_components component_2="Ca" component_1="IKs"/>
<map_variables variable_2="Ca_i" variable_1="Ca_i"/>
</connection>
<connection>
<map_components component_2="Cl" component_1="Ito2"/>
<map_variables variable_2="Cl_i" variable_1="Cl_i"/>
</connection>
<connection>
<map_components component_2="Ca" component_1="Ito2"/>
<map_variables variable_2="Ca_ss" variable_1="Ca_ss"/>
</connection>
<connection>
<map_components component_2="Irel" component_1="Ca"/>
<map_variables variable_2="irelcicr" variable_1="irelcicr"/>
<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="Iup_Ileak" component_1="Ca"/>
<map_variables variable_2="iup" variable_1="iup"/>
<map_variables variable_2="ileak" variable_1="ileak"/>
<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="Idiff_Itr" component_1="Ca"/>
<map_variables variable_2="idiff" variable_1="idiff"/>
<map_variables variable_2="itr" variable_1="itr"/>
<map_variables variable_2="Ca_i" variable_1="Ca_i"/>
<map_variables variable_2="Ca_ss" variable_1="Ca_ss"/>
<map_variables variable_2="Ca_jsr" variable_1="Ca_jsr"/>
<map_variables variable_2="Ca_nsr" variable_1="Ca_nsr"/>
</connection>
<connection>
<map_components component_2="Irel" component_1="ICaL"/>
<map_variables variable_2="CaMKactive" variable_1="CaMKactive"/>
<map_variables variable_2="ibarca" variable_1="ibarca"/>
<map_variables variable_2="ICaL" variable_1="ICaL"/>
</connection>
<connection>
<map_components component_2="Iup_Ileak" component_1="Irel"/>
<map_variables variable_2="KmCaMK" variable_1="KmCaMK"/>
<map_variables variable_2="CaMKactive" variable_1="CaMKactive"/>
</connection>
<connection>
<map_components component_2="Cl" component_1="K"/>
<map_variables variable_2="CTKCl" variable_1="CTKCl"/>
</connection>
<connection>
<map_components component_2="Cl" component_1="Na"/>
<map_variables variable_2="CTNaCl" variable_1="CTNaCl"/>
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In the paper described here, Thomas Hund and Yoram Rudy present a detailed, and physiologically realistic, mathematical model of a canine ventricular cell. Model simulations are able to recreate the rate-dependent phenomena associated with ion-channel kinetics, action potential properties, and calcium ion handling. The model is based on an epicardial myocyte because these cells contain the largest transient outward potassium current (when compared with endocardial or midmyocardial myocytes). The calcium/calmodulin-dependent protein kinase (CaMKII) regulatory pathway was embedded within the electrophysiological model, incorporating calcium-release formulation, calcium subspace, and dynamic chloride handling. Results from the model simulations revealed CaMKII is an important determinant of the rate dependence of the calcium transient, but not of the action potential duration, which depends instead on the ion-channel kinetics.</rdf:value>
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<dc:title>Rate dependence and regulation of action potential and calcium transient in a canine cardiac ventricular cell model</dc:title>
<bqs:volume>110</bqs:volume>
<bqs:first_page>3168</bqs:first_page>
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<dcterms:W3CDTF>2008-06-18T01:17:05+12:00</dcterms:W3CDTF>
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<dc:title>Circulation</dc:title>
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<bqs:Pubmed_id>15505083</bqs:Pubmed_id>
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