- Author:
- James Lawson <j.lawson@auckland.ac.nz>
- Date:
- 2009-07-22 15:45:16+12:00
- Desc:
- Initial commit - committing Penny Noble's file. Added documentation, metadata, fixed e-notation.
- Permanent Source URI:
- http://models.cellml.org/workspace/iyer_hajjar_armoundas_2007/rawfile/5cacbe48996ef45331b50e2dc78b4b469db766ef/iyer_2007_ss.cellml
<?xml version="1.0" encoding="utf-8"?>
<!--
This CellML file was generated on 20/07/2009 at 14:53:30 using:
COR (0.9.31.1297)
Copyright 2002-2009 Dr Alan Garny
http://cor.physiol.ox.ac.uk/ - cor@physiol.ox.ac.uk
CellML 1.0 was used to generate this 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#" name="IyerHajjarArmoundas2007" cmeta:id="IyerHajjarArmoundas2007">
<documentation xmlns="http://cellml.org/tmp-documentation">
<article>
<section id="sec_status">
<title>Model Status</title>
<para> This CellML model is known to run in both COR and OpenCell to recreate the original results.</para>
<para>This model is valid CellML and has consistent units</para>
</section>
<sect1 id="sec_structure">
<title>Model Structure</title>
<para>
ABSTRACT:
</para>
<para>
Catecholaminergic polymorphic ventricular tachycardia is a heritable arrhythmia unmasked by exertion or stress
and is characterized by triggered activity and sudden cardiac death. In this study, we simulated mutations in 2 genes
linked to catecholaminergic polymorphic ventricular tachycardia, the first located in calsequestrin (CSQN2) and the
second in the ryanodine receptor (RyR2). The aim of the study was to investigate the mechanistic basis for spontaneous
Ca2 release events that lead to delayed afterdepolarizations in affected patients. Sarcoplasmic reticulum (SR) luminal
Ca2 sensing was incorporated into a model of the human ventricular myocyte, and CSQN2 mutations were modeled
by simulating disrupted RyR2 luminal Ca2 sensing. In voltage-clamp mode, the mutant CSQN2 model recapitulated
the smaller calcium transients, smaller time to peak calcium transient, and accelerated recovery from inactivation seen
in experiments. In current clamp mode, in the presence of stimulation, we observed delayed afterdepolarizations,
suggesting that accelerated recovery of RyR2 induced by impaired luminal Ca2 sensing underlies the triggered activity
observed in mutant CSQN2-expressing myocytes. In current-clamp mode, in a model of mutant RyR2 that is
characterized by reduced FKBP12.6 binding to the RyR2 on stimulation, the impaired coupled gating characteristic
of these mutations was modeled by reducing cooperativity of RyR2 activation. In current-clamp mode, the mutant RyR2
model exhibited increased diastolic RyR2 open probability that resulted in formation of delayed afterdepolarizations. In
conclusion, these minimal order models of mutant CSQN2 and RyR2 provide plausible mechanisms by which defects
in RyR2 gating may lead to the cellular triggers for arrhythmia, with implications for the development of
targeted therapy.
</para>
<para>
Mechanisms of Abnormal Calcium Homeostasis in Mutations Responsible for Catecholaminergic Polymorphic Ventricular Tachycardia, Vivek Iyer, Roger J. Hajjar, Antonis A. Armoundas, 2007,
<emphasis>Circulation Research</emphasis>,2007 Feb 2;100(2):e22-31.
PubMed ID: 17234962
</para>
</sect1>
</article>
</documentation>
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<variable name="khtrpn_minus" units="per_ms" initial_value="6.6e-5"/>
<variable name="kltrpn_plus" units="per_mM_per_ms" initial_value="40"/>
<variable name="kltrpn_minus" units="per_ms" initial_value="0.04"/>
<variable name="CMDNtot" units="mM" initial_value="0.05"/>
<variable name="CSQNtot" units="mM"/>
<variable name="EGTAtot" units="mM" initial_value="0"/>
<variable name="KmCMDN" units="mM" initial_value="0.00238"/>
<variable name="KmCSQN" units="mM" initial_value="0.8"/>
<variable name="KmEGTA" units="mM" initial_value="0.00015"/>
<variable name="Cai" units="mM" public_interface="in"/>
<variable name="dLTRPNCa" units="per_ms"/>
<variable name="dHTRPNCa" units="per_ms"/>
<variable name="Jtrpn" units="mM_per_ms" public_interface="out"/>
<variable name="CaSS" units="mM" public_interface="in"/>
<variable name="beta_SS" units="dimensionless" public_interface="out"/>
<variable name="beta_JSR" units="dimensionless" public_interface="out"/>
<variable name="beta_i" units="dimensionless" public_interface="out"/>
<variable name="CaJSR" units="mM" public_interface="in"/>
<variable name="LTRPNCa" units="dimensionless" initial_value="0.280466039150394" public_interface="out"/>
<variable name="HTRPNCa" units="dimensionless" initial_value="0.99347761599363" public_interface="out"/>
<variable name="time" units="ms" public_interface="in"/>
<variable name="CSQN2" units="dimensionless" public_interface="in"/>
<variable name="RyR2" units="dimensionless" public_interface="in"/>
<math xmlns="http://www.w3.org/1998/Math/MathML">
<apply>
<eq/>
<ci>CSQNtot</ci>
<piecewise>
<piece>
<cn cellml:units="mM">15</cn>
<apply>
<eq/>
<ci>RyR2</ci>
<cn cellml:units="dimensionless">1</cn>
</apply>
</piece>
<otherwise>
<apply>
<times/>
<cn cellml:units="dimensionless">0.5</cn>
<cn cellml:units="mM">15</cn>
</apply>
</otherwise>
</piecewise>
</apply>
<apply>
<eq/>
<ci>dLTRPNCa</ci>
<apply>
<minus/>
<apply>
<times/>
<ci>kltrpn_plus</ci>
<ci>Cai</ci>
<apply>
<minus/>
<cn cellml:units="dimensionless">1</cn>
<ci>LTRPNCa</ci>
</apply>
</apply>
<apply>
<times/>
<ci>kltrpn_minus</ci>
<ci>LTRPNCa</ci>
</apply>
</apply>
</apply>
<apply>
<eq/>
<ci>dHTRPNCa</ci>
<apply>
<minus/>
<apply>
<times/>
<ci>khtrpn_plus</ci>
<ci>Cai</ci>
<apply>
<minus/>
<cn cellml:units="dimensionless">1</cn>
<ci>HTRPNCa</ci>
</apply>
</apply>
<apply>
<times/>
<ci>khtrpn_minus</ci>
<ci>HTRPNCa</ci>
</apply>
</apply>
</apply>
<apply>
<eq/>
<apply>
<diff/>
<bvar>
<ci>time</ci>
</bvar>
<ci>LTRPNCa</ci>
</apply>
<ci>dLTRPNCa</ci>
</apply>
<apply>
<eq/>
<apply>
<diff/>
<bvar>
<ci>time</ci>
</bvar>
<ci>HTRPNCa</ci>
</apply>
<ci>dHTRPNCa</ci>
</apply>
<apply>
<eq/>
<ci>Jtrpn</ci>
<apply>
<plus/>
<apply>
<times/>
<ci>LTRPNtot</ci>
<ci>dLTRPNCa</ci>
</apply>
<apply>
<times/>
<ci>HTRPNtot</ci>
<ci>dHTRPNCa</ci>
</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>CMDNtot</ci>
<ci>KmCMDN</ci>
</apply>
<apply>
<power/>
<apply>
<plus/>
<ci>CaSS</ci>
<ci>KmCMDN</ci>
</apply>
<cn cellml:units="dimensionless">2</cn>
</apply>
</apply>
<apply>
<divide/>
<apply>
<times/>
<ci>EGTAtot</ci>
<ci>KmEGTA</ci>
</apply>
<apply>
<power/>
<apply>
<plus/>
<ci>CaSS</ci>
<ci>KmEGTA</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>CSQNtot</ci>
<ci>KmCSQN</ci>
</apply>
<apply>
<power/>
<apply>
<plus/>
<ci>CaJSR</ci>
<ci>KmCSQN</ci>
</apply>
<cn cellml:units="dimensionless">2</cn>
</apply>
</apply>
</apply>
</apply>
</apply>
<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>CMDNtot</ci>
<ci>KmCMDN</ci>
</apply>
<apply>
<power/>
<apply>
<plus/>
<ci>Cai</ci>
<ci>KmCMDN</ci>
</apply>
<cn cellml:units="dimensionless">2</cn>
</apply>
</apply>
<apply>
<divide/>
<apply>
<times/>
<ci>EGTAtot</ci>
<ci>KmEGTA</ci>
</apply>
<apply>
<power/>
<apply>
<plus/>
<ci>Cai</ci>
<ci>KmEGTA</ci>
</apply>
<cn cellml:units="dimensionless">2</cn>
</apply>
</apply>
</apply>
</apply>
</apply>
</math>
</component>
<component name="COMPUTE_DERIVATIVES_OF_RyR_RECEPTOR_STATES">
<variable name="kaplus" units="per_uM4_per_ms" initial_value="0.01215"/>
<variable name="kaminus" units="per_ms" initial_value="0.576"/>
<variable name="kbplus" units="per_uM3_per_ms" initial_value="0.00405"/>
<variable name="kbminus" units="per_ms" initial_value="1.93"/>
<variable name="kcplus" units="per_ms" initial_value="0.1"/>
<variable name="kcminus" units="per_ms" initial_value="0.0008"/>
<variable name="ncoop" units="dimensionless" initial_value="4"/>
<variable name="mcoop" units="dimensionless" initial_value="3"/>
<variable name="kryr" units="dimensionless"/>
<variable name="klumenC1O1" units="dimensionless"/>
<variable name="klumenO1C2" units="dimensionless"/>
<variable name="klumenC2O1" units="dimensionless"/>
<variable name="HmaxC1O1" units="dimensionless" initial_value="0.5"/>
<variable name="HmaxO1C2" units="dimensionless"/>
<variable name="HmaxC2O1" units="dimensionless" initial_value="0.5"/>
<variable name="Hmin" units="dimensionless" initial_value="5"/>
<variable name="H50C1O1" units="mM" initial_value="1"/>
<variable name="H50O1C2" units="mM" initial_value="1"/>
<variable name="H50C2O1" units="mM"/>
<variable name="HN" units="dimensionless" initial_value="2.5"/>
<variable name="CaSS" units="mM" public_interface="in"/>
<variable name="CaJSR" units="mM" public_interface="in"/>
<variable name="dC1_RyR" units="per_ms"/>
<variable name="dO2_RyR" units="per_ms"/>
<variable name="dC2_RyR" units="per_ms"/>
<variable name="dO1_RyR" units="per_ms"/>
<variable name="time" units="ms" public_interface="in"/>
<variable name="C1_RyR" units="dimensionless" initial_value="0.132070890861418" public_interface="out"/>
<variable name="O2_RyR" units="dimensionless" initial_value="3.11350788541838e-7" public_interface="out"/>
<variable name="C2_RyR" units="dimensionless" initial_value="0.866791951404883" public_interface="out"/>
<variable name="O1_RyR" units="dimensionless" initial_value="0.00113684728532807" public_interface="out"/>
<variable name="CSQN2" units="dimensionless" public_interface="in"/>
<variable name="RyR2" units="dimensionless" public_interface="in"/>
<math xmlns="http://www.w3.org/1998/Math/MathML">
<apply>
<eq/>
<ci>HmaxO1C2</ci>
<piecewise>
<piece>
<cn cellml:units="dimensionless">0.2</cn>
<apply>
<eq/>
<ci>CSQN2</ci>
<cn cellml:units="dimensionless">1</cn>
</apply>
</piece>
<otherwise>
<cn cellml:units="dimensionless">0.5</cn>
</otherwise>
</piecewise>
</apply>
<apply>
<eq/>
<ci>H50C2O1</ci>
<piecewise>
<piece>
<cn cellml:units="mM">0.5</cn>
<apply>
<eq/>
<ci>CSQN2</ci>
<cn cellml:units="dimensionless">1</cn>
</apply>
</piece>
<otherwise>
<cn cellml:units="mM">1</cn>
</otherwise>
</piecewise>
</apply>
<apply>
<eq/>
<ci>kryr</ci>
<piecewise>
<piece>
<cn cellml:units="dimensionless">0.8</cn>
<apply>
<eq/>
<ci>RyR2</ci>
<cn cellml:units="dimensionless">1</cn>
</apply>
</piece>
<otherwise>
<cn cellml:units="dimensionless">1</cn>
</otherwise>
</piecewise>
</apply>
<apply>
<eq/>
<ci>klumenC1O1</ci>
<apply>
<minus/>
<ci>HmaxC1O1</ci>
<apply>
<divide/>
<apply>
<minus/>
<ci>HmaxC1O1</ci>
<ci>Hmin</ci>
</apply>
<apply>
<plus/>
<cn cellml:units="dimensionless">1</cn>
<apply>
<power/>
<apply>
<divide/>
<ci>H50C1O1</ci>
<ci>CaJSR</ci>
</apply>
<ci>HN</ci>
</apply>
</apply>
</apply>
</apply>
</apply>
<apply>
<eq/>
<ci>klumenO1C2</ci>
<apply>
<minus/>
<ci>HmaxO1C2</ci>
<apply>
<divide/>
<apply>
<minus/>
<ci>HmaxO1C2</ci>
<ci>Hmin</ci>
</apply>
<apply>
<plus/>
<cn cellml:units="dimensionless">1</cn>
<apply>
<power/>
<apply>
<divide/>
<ci>H50O1C2</ci>
<ci>CaJSR</ci>
</apply>
<ci>HN</ci>
</apply>
</apply>
</apply>
</apply>
</apply>
<apply>
<eq/>
<ci>klumenC2O1</ci>
<apply>
<minus/>
<ci>HmaxC2O1</ci>
<apply>
<divide/>
<apply>
<minus/>
<ci>HmaxC2O1</ci>
<ci>Hmin</ci>
</apply>
<apply>
<plus/>
<cn cellml:units="dimensionless">1</cn>
<apply>
<power/>
<apply>
<divide/>
<ci>H50C2O1</ci>
<ci>CaJSR</ci>
</apply>
<ci>HN</ci>
</apply>
</apply>
</apply>
</apply>
</apply>
<apply>
<eq/>
<ci>dC1_RyR</ci>
<apply>
<plus/>
<apply>
<times/>
<apply>
<minus/>
<ci>kaplus</ci>
</apply>
<ci>klumenC1O1</ci>
<apply>
<power/>
<apply>
<times/>
<ci>CaSS</ci>
<cn cellml:units="m2u">1000</cn>
</apply>
<apply>
<times/>
<ci>ncoop</ci>
<ci>kryr</ci>
</apply>
</apply>
<ci>C1_RyR</ci>
</apply>
<apply>
<times/>
<ci>kaminus</ci>
<ci>O1_RyR</ci>
</apply>
</apply>
</apply>
<apply>
<eq/>
<ci>dO2_RyR</ci>
<apply>
<minus/>
<apply>
<times/>
<ci>kbplus</ci>
<apply>
<power/>
<apply>
<times/>
<ci>CaSS</ci>
<cn cellml:units="m2u">1000</cn>
</apply>
<apply>
<times/>
<ci>mcoop</ci>
<ci>kryr</ci>
</apply>
</apply>
<ci>O1_RyR</ci>
</apply>
<apply>
<times/>
<ci>kbminus</ci>
<ci>O2_RyR</ci>
</apply>
</apply>
</apply>
<apply>
<eq/>
<ci>dC2_RyR</ci>
<apply>
<minus/>
<apply>
<times/>
<apply>
<divide/>
<ci>kcplus</ci>
<ci>klumenO1C2</ci>
</apply>
<ci>O1_RyR</ci>
</apply>
<apply>
<times/>
<ci>kcminus</ci>
<ci>klumenC2O1</ci>
<ci>C2_RyR</ci>
</apply>
</apply>
</apply>
<apply>
<eq/>
<ci>dO1_RyR</ci>
<apply>
<minus/>
<apply>
<plus/>
<ci>dC1_RyR</ci>
<ci>dO2_RyR</ci>
<ci>dC2_RyR</ci>
</apply>
</apply>
</apply>
<apply>
<eq/>
<apply>
<diff/>
<bvar>
<ci>time</ci>
</bvar>
<ci>C1_RyR</ci>
</apply>
<ci>dC1_RyR</ci>
</apply>
<apply>
<eq/>
<apply>
<diff/>
<bvar>
<ci>time</ci>
</bvar>
<ci>O2_RyR</ci>
</apply>
<ci>dO2_RyR</ci>
</apply>
<apply>
<eq/>
<apply>
<diff/>
<bvar>
<ci>time</ci>
</bvar>
<ci>C2_RyR</ci>
</apply>
<ci>dC2_RyR</ci>
</apply>
<apply>
<eq/>
<apply>
<diff/>
<bvar>
<ci>time</ci>
</bvar>
<ci>O1_RyR</ci>
</apply>
<ci>dO1_RyR</ci>
</apply>
</math>
</component>
<component name="COMPUTE_DERIVATIVES_OF_LTYPE_CHANNEL_STATES">
<variable name="fL" units="per_ms" initial_value="0.3"/>
<variable name="gL" units="per_ms" initial_value="4"/>
<variable name="bL" units="dimensionless" initial_value="2"/>
<variable name="aL" units="dimensionless" initial_value="2"/>
<variable name="C0_to_C1" units="per_ms"/>
<variable name="C1_to_C2" units="per_ms"/>
<variable name="C2_to_C3" units="per_ms"/>
<variable name="C3_to_C4" units="per_ms"/>
<variable name="C1_to_C0" units="per_ms"/>
<variable name="C2_to_C1" units="per_ms"/>
<variable name="C3_to_C2" units="per_ms"/>
<variable name="C4_to_C3" units="per_ms"/>
<variable name="CCa0_to_CCa1" units="per_ms"/>
<variable name="CCa1_to_CCa2" units="per_ms"/>
<variable name="CCa2_to_CCa3" units="per_ms"/>
<variable name="CCa3_to_CCa4" units="per_ms"/>
<variable name="CCa1_to_CCa0" units="per_ms"/>
<variable name="CCa2_to_CCa1" units="per_ms"/>
<variable name="CCa3_to_CCa2" units="per_ms"/>
<variable name="CCa4_to_CCa3" units="per_ms"/>
<variable name="C0_to_CCa0" units="per_ms"/>
<variable name="C1_to_CCa1" units="per_ms"/>
<variable name="C2_to_CCa2" units="per_ms"/>
<variable name="C3_to_CCa3" units="per_ms"/>
<variable name="C4_to_CCa4" units="per_ms"/>
<variable name="CCa0_to_C0" units="per_ms"/>
<variable name="CCa1_to_C1" units="per_ms"/>
<variable name="CCa2_to_C2" units="per_ms"/>
<variable name="CCa3_to_C3" units="per_ms"/>
<variable name="CCa4_to_C4" units="per_ms"/>
<variable name="V" units="mV" public_interface="in"/>
<variable name="alpha" units="per_ms"/>
<variable name="beta" units="per_ms"/>
<variable name="alpha_prime" units="per_ms"/>
<variable name="beta_prime" units="per_ms"/>
<variable name="gamma" units="per_ms"/>
<variable name="omega" units="per_ms"/>
<variable name="a1_Ca0" units="per_ms"/>
<variable name="a2_Ca0" units="per_ms"/>
<variable name="a1_Ca1" units="per_ms"/>
<variable name="a2_Ca1" units="per_ms"/>
<variable name="a1_Ca2" units="per_ms"/>
<variable name="a2_Ca2" units="per_ms"/>
<variable name="a1_Ca3" units="per_ms"/>
<variable name="a2_Ca3" units="per_ms"/>
<variable name="a1_Ca4" units="per_ms"/>
<variable name="a2_Ca4" units="per_ms"/>
<variable name="a1_C0" units="per_ms"/>
<variable name="a2_C0" units="per_ms"/>
<variable name="a1_C1" units="per_ms"/>
<variable name="a2_C1" units="per_ms"/>
<variable name="a1_C2" units="per_ms"/>
<variable name="a2_C2" units="per_ms"/>
<variable name="a1_C3" units="per_ms"/>
<variable name="a2_C3" units="per_ms"/>
<variable name="a1_C4" units="per_ms"/>
<variable name="a2_C4" units="per_ms"/>
<variable name="CaSS" units="mM" public_interface="in"/>
<variable name="C0" units="dimensionless" initial_value="0.465679150104636"/>
<variable name="C1" units="dimensionless" initial_value="0.00834457719966281"/>
<variable name="C2" units="dimensionless" initial_value="5.60736209083906e-5"/>
<variable name="C3" units="dimensionless" initial_value="1.6747092904465e-7"/>
<variable name="C4" units="dimensionless" initial_value="1.87571666668874e-10"/>
<variable name="CCa0" units="dimensionless" initial_value="0.489846779190386"/>
<variable name="CCa1" units="dimensionless" initial_value="0.035111008610982"/>
<variable name="CCa2" units="dimensionless" initial_value="0.000943745917866092"/>
<variable name="CCa3" units="dimensionless" initial_value="1.12741202215634e-5"/>
<variable name="CCa4" units="dimensionless" initial_value="5.05056944609524e-8"/>
<variable name="time" units="ms" public_interface="in"/>
<variable name="Open" units="dimensionless" initial_value="1.40806027419488e-11" public_interface="out"/>
<variable name="yCa" units="dimensionless" initial_value="0.995434385054729" public_interface="out"/>
<variable name="a1_Cainf" units="dimensionless"/>
<variable name="yCa_inf" units="dimensionless"/>
<variable name="tau_yCa" units="ms"/>
<math xmlns="http://www.w3.org/1998/Math/MathML">
<apply>
<eq/>
<ci>alpha</ci>
<apply>
<times/>
<cn cellml:units="per_ms">4</cn>
<cn cellml:units="dimensionless">1.2</cn>
<cn cellml:units="dimensionless">0.416</cn>
<apply>
<exp/>
<apply>
<times/>
<cn cellml:units="per_mV">0.012</cn>
<apply>
<minus/>
<ci>V</ci>
<cn cellml:units="mV">35</cn>
</apply>
</apply>
</apply>
</apply>
</apply>
<apply>
<eq/>
<ci>beta</ci>
<apply>
<times/>
<cn cellml:units="per_ms">4</cn>
<cn cellml:units="dimensionless">0.45</cn>
<cn cellml:units="dimensionless">0.049</cn>
<apply>
<exp/>
<apply>
<times/>
<apply>
<minus/>
<cn cellml:units="per_mV">0.065</cn>
</apply>
<apply>
<minus/>
<ci>V</ci>
<cn cellml:units="mV">22</cn>
</apply>
</apply>
</apply>
</apply>
</apply>
<apply>
<eq/>
<ci>alpha_prime</ci>
<apply>
<times/>
<ci>aL</ci>
<ci>alpha</ci>
</apply>
</apply>
<apply>
<eq/>
<ci>beta_prime</ci>
<apply>
<divide/>
<ci>beta</ci>
<ci>bL</ci>
</apply>
</apply>
<apply>
<eq/>
<ci>gamma</ci>
<apply>
<times/>
<cn cellml:units="per_ms">0.6</cn>
<cn cellml:units="per_mM">0.09233</cn>
<ci>CaSS</ci>
</apply>
</apply>
<apply>
<eq/>
<ci>omega</ci>
<apply>
<times/>
<cn cellml:units="per_ms">0.25</cn>
<cn cellml:units="dimensionless">0.01</cn>
</apply>
</apply>
<apply>
<eq/>
<ci>C0_to_C1</ci>
<apply>
<times/>
<cn cellml:units="dimensionless">4</cn>
<ci>alpha</ci>
</apply>
</apply>
<apply>
<eq/>
<ci>C1_to_C2</ci>
<apply>
<times/>
<cn cellml:units="dimensionless">3</cn>
<ci>alpha</ci>
</apply>
</apply>
<apply>
<eq/>
<ci>C2_to_C3</ci>
<apply>
<times/>
<cn cellml:units="dimensionless">2</cn>
<ci>alpha</ci>
</apply>
</apply>
<apply>
<eq/>
<ci>C3_to_C4</ci>
<ci>alpha</ci>
</apply>
<apply>
<eq/>
<ci>CCa0_to_CCa1</ci>
<apply>
<times/>
<cn cellml:units="dimensionless">4</cn>
<ci>alpha_prime</ci>
</apply>
</apply>
<apply>
<eq/>
<ci>CCa1_to_CCa2</ci>
<apply>
<times/>
<cn cellml:units="dimensionless">3</cn>
<ci>alpha_prime</ci>
</apply>
</apply>
<apply>
<eq/>
<ci>CCa2_to_CCa3</ci>
<apply>
<times/>
<cn cellml:units="dimensionless">2</cn>
<ci>alpha_prime</ci>
</apply>
</apply>
<apply>
<eq/>
<ci>CCa3_to_CCa4</ci>
<ci>alpha_prime</ci>
</apply>
<apply>
<eq/>
<ci>C1_to_C0</ci>
<ci>beta</ci>
</apply>
<apply>
<eq/>
<ci>C2_to_C1</ci>
<apply>
<times/>
<cn cellml:units="dimensionless">2</cn>
<ci>beta</ci>
</apply>
</apply>
<apply>
<eq/>
<ci>C3_to_C2</ci>
<apply>
<times/>
<cn cellml:units="dimensionless">3</cn>
<ci>beta</ci>
</apply>
</apply>
<apply>
<eq/>
<ci>C4_to_C3</ci>
<apply>
<times/>
<cn cellml:units="dimensionless">4</cn>
<ci>beta</ci>
</apply>
</apply>
<apply>
<eq/>
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<ci>beta_inact14</ci>
<ci>betai0Kv14</ci>
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<apply>
<eq/>
<ci>C0Kv14_to_C1Kv14</ci>
<apply>
<times/>
<cn cellml:units="dimensionless">4</cn>
<ci>alpha_act14</ci>
</apply>
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<apply>
<eq/>
<ci>C1Kv14_to_C2Kv14</ci>
<apply>
<times/>
<cn cellml:units="dimensionless">3</cn>
<ci>alpha_act14</ci>
</apply>
</apply>
<apply>
<eq/>
<ci>C2Kv14_to_C3Kv14</ci>
<apply>
<times/>
<cn cellml:units="dimensionless">2</cn>
<ci>alpha_act14</ci>
</apply>
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<apply>
<eq/>
<ci>C3Kv14_to_OKv14</ci>
<ci>alpha_act14</ci>
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<apply>
<eq/>
<ci>CI0Kv14_to_CI1Kv14</ci>
<apply>
<times/>
<cn cellml:units="dimensionless">4</cn>
<ci>b1Kv14</ci>
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</apply>
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<apply>
<eq/>
<ci>CI1Kv14_to_CI2Kv14</ci>
<apply>
<divide/>
<apply>
<times/>
<cn cellml:units="dimensionless">3</cn>
<ci>b2Kv14</ci>
<ci>alpha_act14</ci>
</apply>
<ci>b1Kv14</ci>
</apply>
</apply>
<apply>
<eq/>
<ci>CI2Kv14_to_CI3Kv14</ci>
<apply>
<divide/>
<apply>
<times/>
<cn cellml:units="dimensionless">2</cn>
<ci>b3Kv14</ci>
<ci>alpha_act14</ci>
</apply>
<ci>b2Kv14</ci>
</apply>
</apply>
<apply>
<eq/>
<ci>CI3Kv14_to_OIKv14</ci>
<apply>
<divide/>
<apply>
<times/>
<ci>b4Kv14</ci>
<ci>alpha_act14</ci>
</apply>
<ci>b3Kv14</ci>
</apply>
</apply>
<apply>
<eq/>
<ci>C1Kv14_to_C0Kv14</ci>
<ci>beta_act14</ci>
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<apply>
<eq/>
<ci>C2Kv14_to_C1Kv14</ci>
<apply>
<times/>
<cn cellml:units="dimensionless">2</cn>
<ci>beta_act14</ci>
</apply>
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<apply>
<eq/>
<ci>C3Kv14_to_C2Kv14</ci>
<apply>
<times/>
<cn cellml:units="dimensionless">3</cn>
<ci>beta_act14</ci>
</apply>
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<apply>
<eq/>
<ci>OKv14_to_C3Kv14</ci>
<apply>
<times/>
<cn cellml:units="dimensionless">4</cn>
<ci>beta_act14</ci>
</apply>
</apply>
<apply>
<eq/>
<ci>CI1Kv14_to_CI0Kv14</ci>
<apply>
<divide/>
<ci>beta_act14</ci>
<ci>f1Kv14</ci>
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<apply>
<eq/>
<ci>CI2Kv14_to_CI1Kv14</ci>
<apply>
<divide/>
<apply>
<times/>
<cn cellml:units="dimensionless">2</cn>
<ci>f1Kv14</ci>
<ci>beta_act14</ci>
</apply>
<ci>f2Kv14</ci>
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<apply>
<eq/>
<ci>CI3Kv14_to_CI2Kv14</ci>
<apply>
<divide/>
<apply>
<times/>
<cn cellml:units="dimensionless">3</cn>
<ci>f2Kv14</ci>
<ci>beta_act14</ci>
</apply>
<ci>f3Kv14</ci>
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<apply>
<eq/>
<ci>OIKv14_to_CI3Kv14</ci>
<apply>
<divide/>
<apply>
<times/>
<cn cellml:units="dimensionless">4</cn>
<ci>f3Kv14</ci>
<ci>beta_act14</ci>
</apply>
<ci>f4Kv14</ci>
</apply>
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<apply>
<eq/>
<ci>C0Kv14_to_CI0Kv14</ci>
<ci>beta_inact14</ci>
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<apply>
<eq/>
<ci>C1Kv14_to_CI1Kv14</ci>
<apply>
<times/>
<ci>f1Kv14</ci>
<ci>beta_inact14</ci>
</apply>
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<apply>
<eq/>
<ci>C2Kv14_to_CI2Kv14</ci>
<apply>
<times/>
<ci>f2Kv14</ci>
<ci>beta_inact14</ci>
</apply>
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<apply>
<eq/>
<ci>C3Kv14_to_CI3Kv14</ci>
<apply>
<times/>
<ci>f3Kv14</ci>
<ci>beta_inact14</ci>
</apply>
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<apply>
<eq/>
<ci>OKv14_to_OIKv14</ci>
<apply>
<times/>
<ci>f4Kv14</ci>
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<eq/>
<ci>CI0Kv14_to_C0Kv14</ci>
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<apply>
<eq/>
<ci>CI1Kv14_to_C1Kv14</ci>
<apply>
<divide/>
<ci>alpha_inact14</ci>
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<eq/>
<ci>CI2Kv14_to_C2Kv14</ci>
<apply>
<divide/>
<ci>alpha_inact14</ci>
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<eq/>
<ci>CI3Kv14_to_C3Kv14</ci>
<apply>
<divide/>
<ci>alpha_inact14</ci>
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</apply>
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<apply>
<eq/>
<ci>OIKv14_to_OKv14</ci>
<apply>
<divide/>
<ci>alpha_inact14</ci>
<ci>b4Kv14</ci>
</apply>
</apply>
<apply>
<eq/>
<ci>a1_C0</ci>
<apply>
<times/>
<apply>
<plus/>
<ci>C0Kv14_to_C1Kv14</ci>
<ci>C0Kv14_to_CI0Kv14</ci>
</apply>
<ci>C0Kv14</ci>
</apply>
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<apply>
<eq/>
<ci>a2_C0</ci>
<apply>
<plus/>
<apply>
<times/>
<ci>C1Kv14_to_C0Kv14</ci>
<ci>C1Kv14</ci>
</apply>
<apply>
<times/>
<ci>CI0Kv14_to_C0Kv14</ci>
<ci>CI0Kv14</ci>
</apply>
</apply>
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<apply>
<eq/>
<apply>
<diff/>
<bvar>
<ci>time</ci>
</bvar>
<ci>C0Kv14</ci>
</apply>
<apply>
<minus/>
<ci>a2_C0</ci>
<ci>a1_C0</ci>
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<apply>
<eq/>
<ci>a1_C1</ci>
<apply>
<times/>
<apply>
<plus/>
<ci>C1Kv14_to_C2Kv14</ci>
<ci>C1Kv14_to_C0Kv14</ci>
<ci>C1Kv14_to_CI1Kv14</ci>
</apply>
<ci>C1Kv14</ci>
</apply>
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<apply>
<eq/>
<ci>a2_C1</ci>
<apply>
<plus/>
<apply>
<times/>
<ci>C2Kv14_to_C1Kv14</ci>
<ci>C2Kv14</ci>
</apply>
<apply>
<times/>
<ci>CI1Kv14_to_C1Kv14</ci>
<ci>CI1Kv14</ci>
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<apply>
<times/>
<ci>C0Kv14_to_C1Kv14</ci>
<ci>C0Kv14</ci>
</apply>
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<apply>
<eq/>
<apply>
<diff/>
<bvar>
<ci>time</ci>
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<ci>C1Kv14</ci>
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<apply>
<minus/>
<ci>a2_C1</ci>
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<eq/>
<ci>a1_C2</ci>
<apply>
<times/>
<apply>
<plus/>
<ci>C2Kv14_to_C3Kv14</ci>
<ci>C2Kv14_to_C1Kv14</ci>
<ci>C2Kv14_to_CI2Kv14</ci>
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<ci>C2Kv14</ci>
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<eq/>
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<plus/>
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<times/>
<ci>C3Kv14_to_C2Kv14</ci>
<ci>C3Kv14</ci>
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<apply>
<times/>
<ci>CI2Kv14_to_C2Kv14</ci>
<ci>CI2Kv14</ci>
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<times/>
<ci>C1Kv14_to_C2Kv14</ci>
<ci>C1Kv14</ci>
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<apply>
<eq/>
<apply>
<diff/>
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<apply>
<minus/>
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<eq/>
<ci>a1_C3</ci>
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<times/>
<apply>
<plus/>
<ci>C3Kv14_to_OKv14</ci>
<ci>C3Kv14_to_C2Kv14</ci>
<ci>C3Kv14_to_CI3Kv14</ci>
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<ci>C3Kv14</ci>
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<eq/>
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<plus/>
<apply>
<times/>
<ci>OKv14_to_C3Kv14</ci>
<ci>OKv14</ci>
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<apply>
<times/>
<ci>CI3Kv14_to_C3Kv14</ci>
<ci>CI3Kv14</ci>
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<times/>
<ci>C2Kv14_to_C3Kv14</ci>
<ci>C2Kv14</ci>
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<apply>
<eq/>
<apply>
<diff/>
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<minus/>
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<eq/>
<ci>a1_O</ci>
<apply>
<times/>
<apply>
<plus/>
<ci>OKv14_to_C3Kv14</ci>
<ci>OKv14_to_OIKv14</ci>
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<ci>OKv14</ci>
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<eq/>
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<plus/>
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<times/>
<ci>C3Kv14_to_OKv14</ci>
<ci>C3Kv14</ci>
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<apply>
<times/>
<ci>OIKv14_to_OKv14</ci>
<ci>OIKv14</ci>
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<apply>
<eq/>
<apply>
<diff/>
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<minus/>
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<eq/>
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<times/>
<apply>
<plus/>
<ci>CI0Kv14_to_C0Kv14</ci>
<ci>CI0Kv14_to_CI1Kv14</ci>
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<ci>CI0Kv14</ci>
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<eq/>
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<plus/>
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<times/>
<ci>C0Kv14_to_CI0Kv14</ci>
<ci>C0Kv14</ci>
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<times/>
<ci>CI1Kv14_to_CI0Kv14</ci>
<ci>CI1Kv14</ci>
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<eq/>
<apply>
<diff/>
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<minus/>
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<eq/>
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<times/>
<apply>
<plus/>
<ci>CI1Kv14_to_CI2Kv14</ci>
<ci>CI1Kv14_to_C1Kv14</ci>
<ci>CI1Kv14_to_CI0Kv14</ci>
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<ci>CI1Kv14</ci>
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<eq/>
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<plus/>
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<times/>
<ci>CI2Kv14_to_CI1Kv14</ci>
<ci>CI2Kv14</ci>
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<times/>
<ci>C1Kv14_to_CI1Kv14</ci>
<ci>C1Kv14</ci>
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<times/>
<ci>CI0Kv14_to_CI1Kv14</ci>
<ci>CI0Kv14</ci>
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<eq/>
<apply>
<diff/>
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<minus/>
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<eq/>
<ci>a1_CI2</ci>
<apply>
<times/>
<apply>
<plus/>
<ci>CI2Kv14_to_CI3Kv14</ci>
<ci>CI2Kv14_to_C2Kv14</ci>
<ci>CI2Kv14_to_CI1Kv14</ci>
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<ci>CI2Kv14</ci>
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<eq/>
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<plus/>
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<times/>
<ci>CI3Kv14_to_CI2Kv14</ci>
<ci>CI3Kv14</ci>
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<times/>
<ci>C2Kv14_to_CI2Kv14</ci>
<ci>C2Kv14</ci>
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<apply>
<times/>
<ci>CI1Kv14_to_CI2Kv14</ci>
<ci>CI1Kv14</ci>
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<diff/>
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<minus/>
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<eq/>
<ci>a1_CI3</ci>
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<times/>
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<plus/>
<ci>CI3Kv14_to_OIKv14</ci>
<ci>CI3Kv14_to_C3Kv14</ci>
<ci>CI3Kv14_to_CI2Kv14</ci>
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<ci>CI3Kv14</ci>
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<eq/>
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<plus/>
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<times/>
<ci>OIKv14_to_CI3Kv14</ci>
<ci>OIKv14</ci>
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<times/>
<ci>C3Kv14_to_CI3Kv14</ci>
<ci>C3Kv14</ci>
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<times/>
<ci>CI2Kv14_to_CI3Kv14</ci>
<ci>CI2Kv14</ci>
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<diff/>
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<minus/>
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<ci>a1_OI</ci>
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<times/>
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<plus/>
<ci>OIKv14_to_OKv14</ci>
<ci>OIKv14_to_CI3Kv14</ci>
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<ci>OIKv14</ci>
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<plus/>
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<times/>
<ci>OKv14_to_OIKv14</ci>
<ci>OKv14</ci>
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<times/>
<ci>CI3Kv14_to_OIKv14</ci>
<ci>CI3Kv14</ci>
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<diff/>
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<minus/>
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<variable name="EK" units="mV" public_interface="out"/>
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<variable name="ECa" units="mV" public_interface="out"/>
<variable name="RT_over_F" units="mV" public_interface="in"/>
<variable name="Nao" units="mM" public_interface="in"/>
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<variable name="Ki" units="mM" public_interface="in"/>
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<variable name="a1" units="mM"/>
<variable name="a2" units="mM"/>
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<times/>
<ci>RT_over_F</ci>
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<ln/>
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<divide/>
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<divide/>
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<times/>
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<ln/>
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<divide/>
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<times/>
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<ci>RT_over_F</ci>
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<ln/>
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<divide/>
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<component name="COMPUTE_INa_IKr_IKs_Ito1_IK1_INab_IKp">
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<variable name="GNab" units="mS_per_uF" initial_value="0.001"/>
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<variable name="GKv43" units="mS_per_uF"/>
<variable name="PKv14" units="litre_per_farad_second"/>
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<variable name="ENa" units="mV" public_interface="in"/>
<variable name="Ko" units="mM" public_interface="in"/>
<variable name="OHerg" units="dimensionless" public_interface="in"/>
<variable name="O1ks" units="dimensionless" public_interface="in"/>
<variable name="O2ks" units="dimensionless" public_interface="in"/>
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<variable name="VF_over_RT" units="dimensionless"/>
<variable name="VFsq_over_RT" units="coulomb_per_millimole"/>
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<variable name="a1_Na" units="mM"/>
<variable name="K1_inf" units="dimensionless"/>
<variable name="IKr" units="uA_per_uF" public_interface="out"/>
<variable name="IKs" units="uA_per_uF" public_interface="out"/>
<variable name="IKv43" units="uA_per_uF" public_interface="out"/>
<variable name="IKv14_K" units="uA_per_uF" public_interface="out"/>
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<variable name="IKv14_Na" units="uA_per_uF" public_interface="out"/>
<variable name="IKv14" units="uA_per_uF" public_interface="out"/>
<variable name="Ito1" units="uA_per_uF" public_interface="out"/>
<variable name="IK1" units="uA_per_uF" public_interface="out"/>
<variable name="INab" units="uA_per_uF" public_interface="out"/>
<variable name="INa" units="uA_per_uF" public_interface="out"/>
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<times/>
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<minus/>
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<ci>Kv43Frac</ci>
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<ci>KvScale</ci>
<cn type="e-notation" cellml:units="litre_per_farad_second">4.2986 <sep/>
-7</cn>
</apply>
</apply>
<apply>
<eq/>
<ci>GKv43</ci>
<apply>
<times/>
<ci>Kv43Frac</ci>
<ci>KvScale</ci>
<cn cellml:units="mS_per_uF">0.1</cn>
</apply>
</apply>
<apply>
<eq/>
<ci>INa</ci>
<apply>
<times/>
<ci>GNa</ci>
<apply>
<plus/>
<ci>na6</ci>
<ci>na7</ci>
</apply>
<apply>
<minus/>
<ci>V</ci>
<ci>ENa</ci>
</apply>
</apply>
</apply>
<apply>
<eq/>
<ci>fKo</ci>
<apply>
<root/>
<apply>
<divide/>
<ci>Ko</ci>
<cn cellml:units="mM">4</cn>
</apply>
</apply>
</apply>
<apply>
<eq/>
<ci>IKr</ci>
<apply>
<times/>
<ci>GKr</ci>
<ci>fKo</ci>
<ci>OHerg</ci>
<apply>
<minus/>
<ci>V</ci>
<ci>EK</ci>
</apply>
</apply>
</apply>
<apply>
<eq/>
<ci>IKs</ci>
<apply>
<times/>
<ci>GKs</ci>
<apply>
<plus/>
<ci>O1ks</ci>
<ci>O2ks</ci>
</apply>
<apply>
<minus/>
<ci>V</ci>
<ci>EK</ci>
</apply>
</apply>
</apply>
<apply>
<eq/>
<ci>IKv43</ci>
<apply>
<times/>
<ci>GKv43</ci>
<ci>OKv43</ci>
<apply>
<minus/>
<ci>V</ci>
<ci>EK</ci>
</apply>
</apply>
</apply>
<apply>
<eq/>
<ci>VF_over_RT</ci>
<apply>
<divide/>
<ci>V</ci>
<ci>RT_over_F</ci>
</apply>
</apply>
<apply>
<eq/>
<ci>VFsq_over_RT</ci>
<apply>
<times/>
<cn cellml:units="dimensionless">1000</cn>
<ci>Faraday</ci>
<ci>VF_over_RT</ci>
</apply>
</apply>
<apply>
<eq/>
<ci>a1_K</ci>
<apply>
<minus/>
<apply>
<times/>
<ci>Ki</ci>
<apply>
<exp/>
<ci>VF_over_RT</ci>
</apply>
</apply>
<ci>Ko</ci>
</apply>
</apply>
<apply>
<eq/>
<ci>a2</ci>
<apply>
<minus/>
<apply>
<exp/>
<ci>VF_over_RT</ci>
</apply>
<cn cellml:units="dimensionless">1</cn>
</apply>
</apply>
<apply>
<eq/>
<ci>IKv14_K</ci>
<apply>
<divide/>
<apply>
<times/>
<ci>PKv14</ci>
<ci>OKv14</ci>
<ci>VFsq_over_RT</ci>
<ci>a1_K</ci>
</apply>
<ci>a2</ci>
</apply>
</apply>
<apply>
<eq/>
<ci>a1_Na</ci>
<apply>
<minus/>
<apply>
<times/>
<ci>Nai</ci>
<apply>
<exp/>
<ci>VF_over_RT</ci>
</apply>
</apply>
<ci>Nao</ci>
</apply>
</apply>
<apply>
<eq/>
<ci>IKv14_Na</ci>
<apply>
<divide/>
<apply>
<times/>
<cn cellml:units="dimensionless">0.02</cn>
<ci>PKv14</ci>
<ci>OKv14</ci>
<ci>VFsq_over_RT</ci>
<ci>a1_Na</ci>
</apply>
<ci>a2</ci>
</apply>
</apply>
<apply>
<eq/>
<ci>IKv14</ci>
<apply>
<plus/>
<ci>IKv14_K</ci>
<ci>IKv14_Na</ci>
</apply>
</apply>
<apply>
<eq/>
<ci>Ito1</ci>
<apply>
<plus/>
<ci>IKv43</ci>
<ci>IKv14</ci>
</apply>
</apply>
<apply>
<eq/>
<ci>K1_inf</ci>
<apply>
<divide/>
<cn cellml:units="dimensionless">1</cn>
<apply>
<plus/>
<cn cellml:units="dimensionless">0.94</cn>
<apply>
<exp/>
<apply>
<times/>
<apply>
<divide/>
<cn cellml:units="dimensionless">1.26</cn>
<ci>RT_over_F</ci>
</apply>
<apply>
<minus/>
<ci>V</ci>
<ci>EK</ci>
</apply>
</apply>
</apply>
</apply>
</apply>
</apply>
<apply>
<eq/>
<ci>IK1</ci>
<apply>
<times/>
<ci>GK1</ci>
<apply>
<root/>
<apply>
<divide/>
<ci>Ko</ci>
<cn cellml:units="mM">1</cn>
</apply>
</apply>
<ci>K1_inf</ci>
<apply>
<minus/>
<ci>V</ci>
<ci>EK</ci>
</apply>
</apply>
</apply>
<apply>
<eq/>
<ci>INab</ci>
<apply>
<times/>
<ci>GNab</ci>
<apply>
<minus/>
<ci>V</ci>
<ci>ENa</ci>
</apply>
</apply>
</apply>
</math>
</component>
<component name="COMPUTE_INaK_INaCa_ICab_IpCa">
<variable name="V" units="mV" public_interface="in"/>
<variable name="ECa" units="mV" public_interface="in"/>
<variable name="RT_over_F" units="mV" public_interface="in"/>
<variable name="Nai" units="mM" public_interface="in"/>
<variable name="Nao" units="mM" public_interface="in"/>
<variable name="Ko" units="mM" public_interface="in"/>
<variable name="Cai" units="mM" public_interface="in"/>
<variable name="Cao" units="mM" public_interface="in"/>
<variable name="kNaCa" units="uA_per_uF" initial_value="0.44"/>
<variable name="KmNa" units="mM" initial_value="87.5"/>
<variable name="KmCa" units="mM" initial_value="1.38"/>
<variable name="ksat" units="dimensionless" initial_value="0.2"/>
<variable name="eta" units="dimensionless" initial_value="0.35"/>
<variable name="INaKmax" units="uA_per_uF" initial_value="2.387"/>
<variable name="KmNai" units="mM" initial_value="20"/>
<variable name="KmKo" units="mM" initial_value="1.5"/>
<variable name="IpCamax" units="uA_per_uF" initial_value="0.05"/>
<variable name="KmpCa" units="mM" initial_value="0.0005"/>
<variable name="GCab" units="mS_per_uF" initial_value="7.684e-5"/>
<variable name="VF_over_RT" units="dimensionless"/>
<variable name="sigma" units="dimensionless"/>
<variable name="a1_Na" units="dimensionless"/>
<variable name="a2_Na" units="dimensionless"/>
<variable name="fNaK" units="dimensionless"/>
<variable name="a1_K" units="dimensionless"/>
<variable name="a2_K" units="dimensionless"/>
<variable name="INaK" units="uA_per_uF" public_interface="out"/>
<variable name="a1_ncx" units="mM4"/>
<variable name="a2_ncx" units="mM4"/>
<variable name="a3_ncx" units="dimensionless"/>
<variable name="a4_ncx" units="mM"/>
<variable name="a5_ncx" units="mM3"/>
<variable name="INaCa" units="uA_per_uF" public_interface="out"/>
<variable name="ICab" units="uA_per_uF" public_interface="out"/>
<variable name="IpCa" units="uA_per_uF" public_interface="out"/>
<math xmlns="http://www.w3.org/1998/Math/MathML">
<apply>
<eq/>
<ci>ICab</ci>
<apply>
<times/>
<ci>GCab</ci>
<apply>
<minus/>
<ci>V</ci>
<ci>ECa</ci>
</apply>
</apply>
</apply>
<apply>
<eq/>
<ci>IpCa</ci>
<apply>
<divide/>
<apply>
<times/>
<ci>IpCamax</ci>
<ci>Cai</ci>
</apply>
<apply>
<plus/>
<ci>KmpCa</ci>
<ci>Cai</ci>
</apply>
</apply>
</apply>
<apply>
<eq/>
<ci>VF_over_RT</ci>
<apply>
<divide/>
<ci>V</ci>
<ci>RT_over_F</ci>
</apply>
</apply>
<apply>
<eq/>
<ci>sigma</ci>
<apply>
<divide/>
<apply>
<minus/>
<apply>
<exp/>
<apply>
<divide/>
<ci>Nao</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>a1_Na</ci>
<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>VF_over_RT</ci>
</apply>
</apply>
</apply>
</apply>
</apply>
<apply>
<eq/>
<ci>a2_Na</ci>
<apply>
<times/>
<cn cellml:units="dimensionless">0.0365</cn>
<ci>sigma</ci>
<apply>
<exp/>
<apply>
<times/>
<apply>
<minus/>
<cn cellml:units="dimensionless">1.33</cn>
</apply>
<ci>VF_over_RT</ci>
</apply>
</apply>
</apply>
</apply>
<apply>
<eq/>
<ci>fNaK</ci>
<apply>
<divide/>
<cn cellml:units="dimensionless">1</cn>
<apply>
<plus/>
<ci>a1_Na</ci>
<ci>a2_Na</ci>
</apply>
</apply>
</apply>
<apply>
<eq/>
<ci>a1_K</ci>
<apply>
<divide/>
<ci>Ko</ci>
<apply>
<plus/>
<ci>Ko</ci>
<ci>KmKo</ci>
</apply>
</apply>
</apply>
<apply>
<eq/>
<ci>a2_K</ci>
<apply>
<plus/>
<cn cellml:units="dimensionless">1</cn>
<apply>
<power/>
<apply>
<divide/>
<ci>KmNai</ci>
<ci>Nai</ci>
</apply>
<cn cellml:units="dimensionless">1.5</cn>
</apply>
</apply>
</apply>
<apply>
<eq/>
<ci>INaK</ci>
<apply>
<divide/>
<apply>
<times/>
<ci>INaKmax</ci>
<ci>fNaK</ci>
<ci>a1_K</ci>
</apply>
<ci>a2_K</ci>
</apply>
</apply>
<apply>
<eq/>
<ci>a1_ncx</ci>
<apply>
<times/>
<apply>
<exp/>
<apply>
<times/>
<ci>eta</ci>
<ci>VF_over_RT</ci>
</apply>
</apply>
<apply>
<power/>
<ci>Nai</ci>
<cn cellml:units="dimensionless">3</cn>
</apply>
<ci>Cao</ci>
</apply>
</apply>
<apply>
<eq/>
<ci>a2_ncx</ci>
<apply>
<times/>
<apply>
<exp/>
<apply>
<times/>
<apply>
<minus/>
<ci>eta</ci>
<cn cellml:units="dimensionless">1</cn>
</apply>
<ci>VF_over_RT</ci>
</apply>
</apply>
<apply>
<power/>
<ci>Nao</ci>
<cn cellml:units="dimensionless">3</cn>
</apply>
<ci>Cai</ci>
</apply>
</apply>
<apply>
<eq/>
<ci>a3_ncx</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>VF_over_RT</ci>
</apply>
</apply>
</apply>
</apply>
</apply>
<apply>
<eq/>
<ci>a4_ncx</ci>
<apply>
<plus/>
<ci>KmCa</ci>
<ci>Cao</ci>
</apply>
</apply>
<apply>
<eq/>
<ci>a5_ncx</ci>
<apply>
<divide/>
<apply>
<plus/>
<apply>
<power/>
<ci>KmNa</ci>
<cn cellml:units="dimensionless">3</cn>
</apply>
<apply>
<power/>
<ci>Nao</ci>
<cn cellml:units="dimensionless">3</cn>
</apply>
</apply>
<cn cellml:units="dimensionless">5000</cn>
</apply>
</apply>
<apply>
<eq/>
<ci>INaCa</ci>
<apply>
<divide/>
<apply>
<times/>
<ci>kNaCa</ci>
<apply>
<minus/>
<ci>a1_ncx</ci>
<ci>a2_ncx</ci>
</apply>
</apply>
<apply>
<times/>
<ci>a4_ncx</ci>
<ci>a3_ncx</ci>
<ci>a5_ncx</ci>
</apply>
</apply>
</apply>
</math>
</component>
<component name="COMPUTE_ICa_ICaK">
<variable name="Ko" units="mM" public_interface="in"/>
<variable name="Ki" units="mM" public_interface="in"/>
<variable name="RT_over_F" units="mV" public_interface="in"/>
<variable name="Cai" units="mM" public_interface="in"/>
<variable name="Cao" units="mM" public_interface="in"/>
<variable name="V" units="mV" public_interface="in"/>
<variable name="yCa" units="dimensionless" public_interface="in"/>
<variable name="Open" units="dimensionless" public_interface="in"/>
<variable name="Faraday" units="coulomb_per_millimole" public_interface="in"/>
<variable name="PKprime" units="litre_per_farad_second"/>
<variable name="VF_over_RT" units="dimensionless"/>
<variable name="VFsq_over_RT" units="coulomb_per_millimole"/>
<variable name="a1_Ca" units="mM"/>
<variable name="a2_Ca" units="dimensionless"/>
<variable name="a1_K" units="mM"/>
<variable name="a2_K" units="dimensionless"/>
<variable name="ICa" units="uA_per_uF" public_interface="out"/>
<variable name="ICaK" units="uA_per_uF" public_interface="out"/>
<variable name="ICamax" units="uA_per_uF"/>
<variable name="Icabar" units="uA_per_uF"/>
<variable name="PCa" units="litre_per_farad_second"/>
<variable name="PK" units="litre_per_farad_second"/>
<variable name="ICahalf" units="uA_per_uF" initial_value="-0.265"/>
<variable name="Pscale" units="dimensionless" initial_value="7"/>
<variable name="iso" units="dimensionless" public_interface="in"/>
<math xmlns="http://www.w3.org/1998/Math/MathML">
<apply>
<eq/>
<ci>PK</ci>
<apply>
<times/>
<ci>Pscale</ci>
<cn type="e-notation" cellml:units="litre_per_farad_second">4.574 <sep/>
-7</cn>
</apply>
</apply>
<apply>
<eq/>
<ci>PCa</ci>
<piecewise>
<piece>
<apply>
<times/>
<ci>Pscale</ci>
<cn type="e-notation" cellml:units="litre_per_farad_second">2.469 <sep/>
-4</cn>
</apply>
<apply>
<eq/>
<ci>iso</ci>
<cn cellml:units="dimensionless">0</cn>
</apply>
</piece>
<otherwise>
<apply>
<times/>
<cn cellml:units="dimensionless">1.5</cn>
<ci>Pscale</ci>
<cn type="e-notation" cellml:units="litre_per_farad_second">2.469 <sep/>
-4</cn>
</apply>
</otherwise>
</piecewise>
</apply>
<apply>
<eq/>
<ci>VF_over_RT</ci>
<apply>
<divide/>
<ci>V</ci>
<ci>RT_over_F</ci>
</apply>
</apply>
<apply>
<eq/>
<ci>VFsq_over_RT</ci>
<apply>
<times/>
<cn cellml:units="dimensionless">1000</cn>
<ci>Faraday</ci>
<ci>VF_over_RT</ci>
</apply>
</apply>
<apply>
<eq/>
<ci>a1_Ca</ci>
<apply>
<minus/>
<apply>
<times/>
<cn type="e-notation" cellml:units="mM">1 <sep/>
-3</cn>
<apply>
<exp/>
<apply>
<times/>
<cn cellml:units="dimensionless">2</cn>
<ci>VF_over_RT</ci>
</apply>
</apply>
</apply>
<apply>
<times/>
<ci>Cao</ci>
<cn cellml:units="dimensionless">0.341</cn>
</apply>
</apply>
</apply>
<apply>
<eq/>
<ci>a2_Ca</ci>
<apply>
<minus/>
<apply>
<exp/>
<apply>
<times/>
<cn cellml:units="dimensionless">2</cn>
<ci>VF_over_RT</ci>
</apply>
</apply>
<cn cellml:units="dimensionless">1</cn>
</apply>
</apply>
<apply>
<eq/>
<ci>ICamax</ci>
<apply>
<divide/>
<apply>
<times/>
<ci>PCa</ci>
<cn cellml:units="dimensionless">4</cn>
<ci>VFsq_over_RT</ci>
<ci>a1_Ca</ci>
</apply>
<ci>a2_Ca</ci>
</apply>
</apply>
<apply>
<eq/>
<ci>ICa</ci>
<apply>
<times/>
<ci>ICamax</ci>
<ci>yCa</ci>
<ci>Open</ci>
</apply>
</apply>
<apply>
<eq/>
<ci>Icabar</ci>
<piecewise>
<piece>
<cn cellml:units="uA_per_uF">0</cn>
<apply>
<geq/>
<ci>ICamax</ci>
<cn cellml:units="uA_per_uF">0</cn>
</apply>
</piece>
<otherwise>
<ci>ICamax</ci>
</otherwise>
</piecewise>
</apply>
<apply>
<eq/>
<ci>PKprime</ci>
<apply>
<divide/>
<ci>PK</ci>
<apply>
<plus/>
<cn cellml:units="dimensionless">1</cn>
<apply>
<divide/>
<ci>Icabar</ci>
<ci>ICahalf</ci>
</apply>
</apply>
</apply>
</apply>
<apply>
<eq/>
<ci>a1_K</ci>
<apply>
<minus/>
<apply>
<times/>
<ci>Ki</ci>
<apply>
<exp/>
<ci>VF_over_RT</ci>
</apply>
</apply>
<ci>Ko</ci>
</apply>
</apply>
<apply>
<eq/>
<ci>a2_K</ci>
<apply>
<minus/>
<apply>
<exp/>
<ci>VF_over_RT</ci>
</apply>
<cn cellml:units="dimensionless">1</cn>
</apply>
</apply>
<apply>
<eq/>
<ci>ICaK</ci>
<apply>
<divide/>
<apply>
<times/>
<ci>PKprime</ci>
<ci>Open</ci>
<ci>yCa</ci>
<ci>VFsq_over_RT</ci>
<ci>a1_K</ci>
</apply>
<ci>a2_K</ci>
</apply>
</apply>
</math>
</component>
<component name="INa">
<variable name="V" units="mV" public_interface="in"/>
<variable name="time" units="ms" public_interface="in"/>
<variable name="Temp_Scale" units="dimensionless"/>
<variable name="alpha1" units="per_ms"/>
<variable name="beta1" units="per_ms"/>
<variable name="gamma1" units="per_ms"/>
<variable name="Delta1" units="per_ms"/>
<variable name="On" units="per_ms"/>
<variable name="Of" units="per_ms"/>
<variable name="GammaGamma" units="per_ms"/>
<variable name="DeltaDelta" units="per_ms"/>
<variable name="epsilon" units="per_ms"/>
<variable name="omega_na" units="per_ms"/>
<variable name="rho" units="per_ms"/>
<variable name="mu" units="per_ms"/>
<variable name="Cn" units="per_ms"/>
<variable name="Cf" units="per_ms"/>
<variable name="parameter_a" units="dimensionless"/>
<variable name="k12" units="per_ms"/>
<variable name="k23" units="per_ms"/>
<variable name="k34" units="per_ms"/>
<variable name="k45" units="per_ms"/>
<variable name="k56" units="per_ms"/>
<variable name="k67" units="per_ms"/>
<variable name="k89" units="per_ms"/>
<variable name="k910" units="per_ms"/>
<variable name="k1011" units="per_ms"/>
<variable name="k1112" units="per_ms"/>
<variable name="k1213" units="per_ms"/>
<variable name="k57" units="per_ms"/>
<variable name="k21" units="per_ms"/>
<variable name="k32" units="per_ms"/>
<variable name="k43" units="per_ms"/>
<variable name="k54" units="per_ms"/>
<variable name="k65" units="per_ms"/>
<variable name="k76" units="per_ms"/>
<variable name="k98" units="per_ms"/>
<variable name="k109" units="per_ms"/>
<variable name="k1110" units="per_ms"/>
<variable name="k1211" units="per_ms"/>
<variable name="k1312" units="per_ms"/>
<variable name="k75" units="per_ms"/>
<variable name="k81" units="per_ms"/>
<variable name="k92" units="per_ms"/>
<variable name="k103" units="per_ms"/>
<variable name="k114" units="per_ms"/>
<variable name="k125" units="per_ms"/>
<variable name="k136" units="per_ms"/>
<variable name="k18" units="per_ms"/>
<variable name="k29" units="per_ms"/>
<variable name="k310" units="per_ms"/>
<variable name="k411" units="per_ms"/>
<variable name="k512" units="per_ms"/>
<variable name="k613" units="per_ms"/>
<variable name="na1" units="dimensionless" initial_value="0.111284526171411" public_interface="out"/>
<variable name="na2" units="dimensionless" initial_value="0.0481019786429977" public_interface="out"/>
<variable name="na3" units="dimensionless" initial_value="0.00779692701457915" public_interface="out"/>
<variable name="na4" units="dimensionless" initial_value="0.000561699600929369" public_interface="out"/>
<variable name="na5" units="dimensionless" initial_value="1.51746424723121e-5" public_interface="out"/>
<variable name="na6" units="dimensionless" initial_value="1.02118700961583e-7" public_interface="out"/>
<variable name="na7" units="dimensionless" initial_value="1.93499158844817e-8" public_interface="out"/>
<variable name="na8" units="dimensionless" initial_value="0.368582741846592" public_interface="out"/>
<variable name="na9" units="dimensionless" initial_value="0.312463212648791" public_interface="out"/>
<variable name="na10" units="dimensionless" initial_value="0.0993398770493615" public_interface="out"/>
<variable name="na11" units="dimensionless" initial_value="0.0140431688972267" public_interface="out"/>
<variable name="na12" units="dimensionless" initial_value="0.000750073829883749" public_interface="out"/>
<variable name="na13" units="dimensionless" initial_value="0.0370604970714329" public_interface="out"/>
<variable name="TNa" units="kelvin" initial_value="294.16"/>
<variable name="KToverH" units="per_ms"/>
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<plus/>
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<ci>k136</ci>
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<variable name="A0_HERG" units="per_ms" initial_value="0.017147641733086"/>
<variable name="B0_HERG" units="per_mV" initial_value="0.03304608038835"/>
<variable name="A1_HERG" units="per_ms" initial_value="0.03969328381141"/>
<variable name="B1_HERG" units="per_mV" initial_value="-0.0430605416398"/>
<variable name="A2_HERG" units="per_ms" initial_value="0.02057448605977"/>
<variable name="B2_HERG" units="per_mV" initial_value="0.02617412715118"/>
<variable name="A3_HERG" units="per_ms" initial_value="0.00134366604423"/>
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<variable name="A4_HERG" units="per_ms" initial_value="0.10666316491288"/>
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<variable name="B5_HERG" units="per_mV" initial_value="-0.04536642959543"/>
<variable name="A6_HERG" units="per_ms" initial_value="8.039374403e-5"/>
<variable name="B6_HERG" units="per_mV" initial_value="6.9808924e-7"/>
<variable name="C2H_to_C3H" units="per_ms"/>
<variable name="C3H_to_C2H" units="per_ms"/>
<variable name="C1H_to_C2H" units="per_ms"/>
<variable name="C2H_to_C1H" units="per_ms"/>
<variable name="C3H_to_OH" units="per_ms"/>
<variable name="OH_to_C3H" units="per_ms"/>
<variable name="OH_to_IH" units="per_ms"/>
<variable name="IH_to_OH" units="per_ms"/>
<variable name="C3H_to_IH" units="per_ms"/>
<variable name="IH_to_C3H" units="per_ms"/>
<variable name="V" units="mV" public_interface="in"/>
<variable name="C1Herg" units="dimensionless" initial_value="0.994948338598163" public_interface="out"/>
<variable name="a1_C2" units="per_ms"/>
<variable name="a2_C2" units="per_ms"/>
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<variable name="a2_C3" units="per_ms"/>
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<variable name="a1_O" units="per_ms"/>
<variable name="a2_O" units="per_ms"/>
<variable name="OHerg" units="dimensionless" initial_value="0.00120284688677794" public_interface="out"/>
<variable name="a1_I" units="per_ms"/>
<variable name="a2_I" units="per_ms"/>
<variable name="IHerg" units="dimensionless" initial_value="0.000243789721526602" public_interface="out"/>
<variable name="time" units="ms" public_interface="in"/>
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<eq/>
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<times/>
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<times/>
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<ci>A0_HERG</ci>
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<exp/>
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<times/>
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<times/>
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<ci>A4_HERG</ci>
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<ci>V</ci>
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<eq/>
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<times/>
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<ci>A6_HERG</ci>
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<exp/>
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<ci>B6_HERG</ci>
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<apply>
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<apply>
<divide/>
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<ci>OH_to_C3H</ci>
<ci>IH_to_OH</ci>
<ci>C3H_to_IH</ci>
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<ci>C3H_to_OH</ci>
<ci>OH_to_IH</ci>
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<diff/>
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<ci>time</ci>
</bvar>
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<minus/>
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<times/>
<ci>C2H_to_C1H</ci>
<ci>C2Herg</ci>
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<times/>
<ci>C1H_to_C2H</ci>
<ci>C1Herg</ci>
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<ci>C1Herg</ci>
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<ci>C3H_to_C2H</ci>
<ci>C3Herg</ci>
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<ci>C2H_to_C3H</ci>
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<ci>C2H_to_C3H</ci>
<ci>C2Herg</ci>
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<ci>OH_to_C3H</ci>
<ci>OHerg</ci>
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<ci>IHerg</ci>
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<times/>
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<ci>C3Herg</ci>
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<ci>OH_to_IH</ci>
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<ci>OHerg</ci>
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<plus/>
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<times/>
<ci>C3H_to_IH</ci>
<ci>C3Herg</ci>
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<apply>
<times/>
<ci>OH_to_IH</ci>
<ci>OHerg</ci>
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<ci>a2_I</ci>
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<times/>
<apply>
<plus/>
<ci>IH_to_C3H</ci>
<ci>IH_to_OH</ci>
</apply>
<ci>IHerg</ci>
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<eq/>
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<ci>IHerg</ci>
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<apply>
<minus/>
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</apply>
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<component name="IKs">
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<variable name="C1ks_O1ks" units="per_ms"/>
<variable name="O1ks_O2ks" units="per_ms"/>
<variable name="O1ks_C1ks" units="per_ms"/>
<variable name="O2ks_O1ks" units="per_ms"/>
<variable name="C1ks_C0ks" units="per_ms"/>
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<variable name="O2ks" units="dimensionless" initial_value="0.0258818770122187" public_interface="out"/>
<variable name="V" units="mV" public_interface="in"/>
<variable name="time" units="ms" public_interface="in"/>
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<eq/>
<ci>C0ks_C1ks</ci>
<cn cellml:units="per_ms">0.00795600798004</cn>
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<eq/>
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<ci>O1ks_O2ks</ci>
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<times/>
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<ci>V</ci>
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<eq/>
<ci>O1ks_C1ks</ci>
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<minus/>
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<ci>V</ci>
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<eq/>
<ci>O2ks_O1ks</ci>
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<ci>V</ci>
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<eq/>
<ci>C1ks_C0ks</ci>
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<times/>
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<minus/>
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<ci>V</ci>
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<plus/>
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<times/>
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<minus/>
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<ci>C0ks</ci>
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<times/>
<ci>C1ks_C0ks</ci>
<ci>C1ks</ci>
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<ci>C1ks</ci>
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<plus/>
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<minus/>
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<times/>
<ci>C0ks_C1ks</ci>
<ci>C0ks</ci>
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<times/>
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<plus/>
<ci>C1ks_C0ks</ci>
<ci>C1ks_O1ks</ci>
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<ci>C1ks</ci>
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<times/>
<ci>O1ks_C1ks</ci>
<ci>O1ks</ci>
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<ci>O1ks</ci>
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<plus/>
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<minus/>
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<times/>
<ci>C1ks_O1ks</ci>
<ci>C1ks</ci>
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<times/>
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<plus/>
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<ci>O1ks_O2ks</ci>
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<ci>O1ks</ci>
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<times/>
<ci>O2ks_O1ks</ci>
<ci>O2ks</ci>
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<bvar>
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<ci>O2ks</ci>
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<minus/>
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<times/>
<ci>O1ks_O2ks</ci>
<ci>O1ks</ci>
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<apply>
<times/>
<ci>O2ks_O1ks</ci>
<ci>O2ks</ci>
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</component>
<connection>
<map_components component_1="environment" component_2="IKs"/>
<map_variables variable_1="time" variable_2="time"/>
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<connection>
<map_components component_1="environment" component_2="COMPUTE_CONCENTRATION_AND_VOLTAGE_DERIVATIVES"/>
<map_variables variable_1="time" variable_2="time"/>
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<connection>
<map_components component_1="environment" component_2="IKr"/>
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<connection>
<map_components component_1="environment" component_2="INa"/>
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<connection>
<map_components component_1="environment" component_2="COMPUTE_DERIVATIVES_OF_Kv1_4_CHANNEL_STATES"/>
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<connection>
<map_components component_1="environment" component_2="COMPUTE_DERIVATIVES_OF_Kv4_3_CHANNEL_STATES"/>
<map_variables variable_1="time" variable_2="time"/>
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<connection>
<map_components component_1="environment" component_2="COMPUTE_DERIVATIVES_OF_LTYPE_CHANNEL_STATES"/>
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<connection>
<map_components component_1="environment" component_2="COMPUTE_DERIVATIVES_OF_RyR_RECEPTOR_STATES"/>
<map_variables variable_1="time" variable_2="time"/>
<map_variables variable_1="CSQN2" variable_2="CSQN2"/>
<map_variables variable_1="RyR2" variable_2="RyR2"/>
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<connection>
<map_components component_1="environment" component_2="COMPUTE_Jtrpn_and_BUFFER_SCALE_FACTORS"/>
<map_variables variable_1="time" variable_2="time"/>
<map_variables variable_1="CSQN2" variable_2="CSQN2"/>
<map_variables variable_1="RyR2" variable_2="RyR2"/>
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<connection>
<map_components component_1="environment" component_2="I_stimulus"/>
<map_variables variable_1="time" variable_2="time"/>
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<connection>
<map_components component_1="environment" component_2="COMPUTE_ICa_ICaK"/>
<map_variables variable_1="iso" variable_2="iso"/>
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<connection>
<map_components component_1="environment" component_2="COMPUTE_INTRACELLULAR_CALCIUM_FLUXES"/>
<map_variables variable_1="iso" variable_2="iso"/>
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<connection>
<map_components component_1="COMPUTE_CONCENTRATION_AND_VOLTAGE_DERIVATIVES" component_2="IKs"/>
<map_variables variable_1="V" variable_2="V"/>
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<connection>
<map_components component_1="COMPUTE_CONCENTRATION_AND_VOLTAGE_DERIVATIVES" component_2="IKr"/>
<map_variables variable_1="V" variable_2="V"/>
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<connection>
<map_components component_1="COMPUTE_CONCENTRATION_AND_VOLTAGE_DERIVATIVES" component_2="INa"/>
<map_variables variable_1="V" variable_2="V"/>
<map_variables variable_1="RT_over_F" variable_2="RToverF"/>
<map_variables variable_1="Faraday" variable_2="Faraday"/>
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