- Author:
- Hanne <Hanne@hanne-nielsens-macbook.local>
- Date:
- 2010-04-19 12:52:38+12:00
- Desc:
- Added smaller svg file, integrated new image into session file
- Permanent Source URI:
- https://models.fieldml.org/workspace/michailova_mcculloch_2001/rawfile/74804747579f0b3310bb693d30c684067518e681/michailova_mcculloch_2001.cellml
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<title>Model study of ATP and ADP buffering, transport of Ca(2+) and Mg(2+), and regulation of ion pumps in ventricular myocyte</title>
<author>
<firstname>Catherine</firstname>
<surname>Lloyd</surname>
<affiliation>
<shortaffil>Auckland Bioengineering Institute, The University of Auckland</shortaffil>
</affiliation>
</author>
</articleinfo>
<section id="sec_status">
<title>Model Status</title>
<para>
This CellML model runs in both COR and OpenCell to recreate the published results. The units have been checked and they are consistent. We thank the original model author Anushka Michailova for providing us with the MATLAB code for this model. Please note when running a simultaion the step size has to be smaller than 0.005 seconds.
</para>
</section>
<sect1 id="sec_structure">
<title>Model Structure</title>
<para>
ABSTRACT: We extended the model of the ventricular myocyte by Winslow et al. (Circ. Res 1999, 84:571-586) by incorporating equations for Ca(2+) and Mg(2+) buffering and transport by ATP and ADP and equations for MgATP regulation of ion transporters (Na(+)-K(+) pump, sarcolemmal and sarcoplasmic Ca(2+) pumps). The results indicate that, under normal conditions, Ca(2+) binding by low-affinity ATP and diffusion of CaATP may affect the amplitude and time course of intracellular Ca(2+) signals. The model also suggests that a fall in ATP/ADP ratio significantly reduces sarcoplasmic Ca(2+) content, increases diastolic Ca(2+), lowers systolic Ca(2+), increases Ca(2+) influx through L-type channels, and decreases the efficiency of the Na(+)/Ca(2+) exchanger in extruding Ca(2+) during periodic voltage-clamp stimulation. The analysis suggests that the most important reason for these changes during metabolic inhibition is the down-regulation of the sarcoplasmic Ca(2+)-ATPase pump by reduced diastolic MgATP levels. High Ca(2+) concentrations developed near the membrane might have a greater influence on Mg(2+), ATP, and ADP concentrations than that of the lower Ca(2+) concentrations in the bulk myoplasm. The model predictions are in general agreement with experimental observations measured under normal and pathological conditions.
</para>
<para>
The original paper reference is cited below:
</para>
<para>
Model study of ATP and ADP buffering, transport of Ca(2+) and Mg(2+), and regulation of ion pumps in ventricular myocyte, Anushka Michailova and Andrew McCulloch, 2001, <emphasis>Biophysical Journal</emphasis>, 81, 614-629. <ulink url="http://www.ncbi.nlm.nih.gov/pubmed/11463611">PubMed ID: 11463611</ulink>
</para>
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<caption>Schematic diagram of the mechanisms involved in the model.</caption>
</informalfigure>
</sect1>
</article>
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<cn xmlns:cellml="http://www.cellml.org/cellml/1.0#" cellml:units="per_millivolt">0.1378</cn>
</apply>
<apply>
<plus/>
<ci>V</ci>
<cn xmlns:cellml="http://www.cellml.org/cellml/1.0#" cellml:units="millivolt">40.14</cn>
</apply>
</apply>
</apply>
</apply>
</apply>
<apply>
<lt/>
<ci>V</ci>
<apply>
<minus/>
<cn xmlns:cellml="http://www.cellml.org/cellml/1.0#" cellml:units="millivolt">40</cn>
</apply>
</apply>
</piece>
<otherwise>
<apply>
<divide/>
<apply>
<times/>
<cn xmlns:cellml="http://www.cellml.org/cellml/1.0#" cellml:units="per_second">300</cn>
<apply>
<exp/>
<apply>
<times/>
<apply>
<minus/>
<cn xmlns:cellml="http://www.cellml.org/cellml/1.0#" cellml:units="per_millivolt">0.0000002535</cn>
</apply>
<ci>V</ci>
</apply>
</apply>
</apply>
<apply>
<plus/>
<cn xmlns:cellml="http://www.cellml.org/cellml/1.0#" cellml:units="dimensionless">1</cn>
<apply>
<exp/>
<apply>
<times/>
<apply>
<minus/>
<cn xmlns:cellml="http://www.cellml.org/cellml/1.0#" cellml:units="per_millivolt">0.1</cn>
</apply>
<apply>
<plus/>
<ci>V</ci>
<cn xmlns:cellml="http://www.cellml.org/cellml/1.0#" cellml:units="millivolt">32</cn>
</apply>
</apply>
</apply>
</apply>
</apply>
</otherwise>
</piecewise>
</apply>
<apply>
<eq/>
<apply>
<diff/>
<bvar>
<ci>time</ci>
</bvar>
<ci>j</ci>
</apply>
<apply>
<minus/>
<apply>
<times/>
<ci>alpha_j</ci>
<apply>
<minus/>
<cn xmlns:cellml="http://www.cellml.org/cellml/1.0#" cellml:units="dimensionless">1</cn>
<ci>j</ci>
</apply>
</apply>
<apply>
<times/>
<ci>beta_j</ci>
<ci>j</ci>
</apply>
</apply>
</apply>
</math>
</component>
<component name="rapid_activating_delayed_rectifiyer_K_current">
<variable cmeta:id="rapid_activating_delayed_rectifiyer_K_current_i_Kr" name="i_Kr" public_interface="out" units="microA_per_microF"/>
<variable name="E_K" public_interface="out" units="millivolt"/>
<variable initial_value="0.0034" name="g_Kr" units="milliS_per_microF"/>
<variable name="f_K_o" units="dimensionless"/>
<variable name="R_V" units="dimensionless"/>
<variable name="time" private_interface="out" public_interface="in" units="second"/>
<variable name="V" private_interface="out" public_interface="in" units="millivolt"/>
<variable name="K_o" public_interface="in" units="millimolar"/>
<variable name="K_i" public_interface="in" units="millimolar"/>
<variable name="R" public_interface="in" units="joule_per_mole_kelvin"/>
<variable name="T" public_interface="in" units="kelvin"/>
<variable name="F" public_interface="in" units="coulomb_per_millimole"/>
<variable name="X_kr" private_interface="in" units="dimensionless"/>
<math xmlns="http://www.w3.org/1998/Math/MathML">
<apply>
<eq/>
<ci>E_K</ci>
<apply>
<times/>
<apply>
<divide/>
<apply>
<times/>
<ci>R</ci>
<ci>T</ci>
</apply>
<ci>F</ci>
</apply>
<apply>
<ln/>
<apply>
<divide/>
<ci>K_o</ci>
<ci>K_i</ci>
</apply>
</apply>
</apply>
</apply>
<apply>
<eq/>
<ci>f_K_o</ci>
<apply>
<root/>
<apply>
<divide/>
<ci>K_o</ci>
<cn xmlns:cellml="http://www.cellml.org/cellml/1.0#" cellml:units="millimolar">4</cn>
</apply>
</apply>
</apply>
<apply>
<eq/>
<ci>R_V</ci>
<apply>
<divide/>
<cn xmlns:cellml="http://www.cellml.org/cellml/1.0#" cellml:units="dimensionless">1</cn>
<apply>
<plus/>
<cn xmlns:cellml="http://www.cellml.org/cellml/1.0#" cellml:units="dimensionless">1</cn>
<apply>
<times/>
<cn xmlns:cellml="http://www.cellml.org/cellml/1.0#" cellml:units="dimensionless">1.4945</cn>
<apply>
<exp/>
<apply>
<times/>
<cn xmlns:cellml="http://www.cellml.org/cellml/1.0#" cellml:units="per_millivolt">0.0446</cn>
<ci>V</ci>
</apply>
</apply>
</apply>
</apply>
</apply>
</apply>
<apply>
<eq/>
<ci>i_Kr</ci>
<apply>
<times/>
<ci>g_Kr</ci>
<ci>f_K_o</ci>
<ci>R_V</ci>
<ci>X_kr</ci>
<apply>
<minus/>
<ci>V</ci>
<ci>E_K</ci>
</apply>
</apply>
</apply>
</math>
</component>
<component name="rapid_activating_delayed_rectifiyer_K_current_X_kr_gate">
<variable initial_value="0.51" name="X_kr" public_interface="out" units="dimensionless"/>
<variable name="K12" units="dimensionless"/>
<variable name="K21" units="dimensionless"/>
<variable name="X_kr_inf" units="dimensionless"/>
<variable name="tau_X_kr" units="second"/>
<variable initial_value="1" name="tau_factor" units="dimensionless"/>
<variable name="V" public_interface="in" units="millivolt"/>
<variable name="time" public_interface="in" units="second"/>
<math xmlns="http://www.w3.org/1998/Math/MathML">
<apply>
<eq/>
<ci>K12</ci>
<apply>
<exp/>
<apply>
<plus/>
<apply>
<minus/>
<cn xmlns:cellml="http://www.cellml.org/cellml/1.0#" cellml:units="dimensionless">5.495</cn>
</apply>
<apply>
<times/>
<cn xmlns:cellml="http://www.cellml.org/cellml/1.0#" cellml:units="per_millivolt">0.1691</cn>
<ci>V</ci>
</apply>
</apply>
</apply>
</apply>
<apply>
<eq/>
<ci>K21</ci>
<apply>
<exp/>
<apply>
<minus/>
<apply>
<minus/>
<cn xmlns:cellml="http://www.cellml.org/cellml/1.0#" cellml:units="dimensionless">7.677</cn>
</apply>
<apply>
<times/>
<cn xmlns:cellml="http://www.cellml.org/cellml/1.0#" cellml:units="per_millivolt">0.0128</cn>
<ci>V</ci>
</apply>
</apply>
</apply>
</apply>
<apply>
<eq/>
<ci>X_kr_inf</ci>
<apply>
<divide/>
<ci>K12</ci>
<apply>
<plus/>
<ci>K12</ci>
<ci>K21</ci>
</apply>
</apply>
</apply>
<apply>
<eq/>
<ci>tau_X_kr</ci>
<apply>
<plus/>
<apply>
<divide/>
<cn xmlns:cellml="http://www.cellml.org/cellml/1.0#" cellml:units="second">0.001</cn>
<apply>
<plus/>
<ci>K12</ci>
<ci>K21</ci>
</apply>
</apply>
<apply>
<times/>
<ci>tau_factor</ci>
<cn xmlns:cellml="http://www.cellml.org/cellml/1.0#" cellml:units="second">0.027</cn>
</apply>
</apply>
</apply>
<apply>
<eq/>
<apply>
<diff/>
<bvar>
<ci>time</ci>
</bvar>
<ci>X_kr</ci>
</apply>
<apply>
<divide/>
<apply>
<minus/>
<ci>X_kr_inf</ci>
<ci>X_kr</ci>
</apply>
<ci>tau_X_kr</ci>
</apply>
</apply>
</math>
</component>
<component name="slow_activating_delayed_rectifiyer_K_current">
<variable cmeta:id="slow_activating_delayed_rectifiyer_K_current_i_Ks" name="i_Ks" public_interface="out" units="microA_per_microF"/>
<variable initial_value="0.0027134" name="g_Ks" units="milliS_per_microF"/>
<variable name="E_Ks" units="millivolt"/>
<variable name="time" private_interface="out" public_interface="in" units="second"/>
<variable name="V" private_interface="out" public_interface="in" units="millivolt"/>
<variable name="K_o" public_interface="in" units="millimolar"/>
<variable name="K_i" public_interface="in" units="millimolar"/>
<variable name="Na_o" public_interface="in" units="millimolar"/>
<variable name="Na_i" public_interface="in" units="millimolar"/>
<variable name="R" public_interface="in" units="joule_per_mole_kelvin"/>
<variable name="T" public_interface="in" units="kelvin"/>
<variable name="F" public_interface="in" units="coulomb_per_millimole"/>
<variable name="X_ks" private_interface="in" units="dimensionless"/>
<math xmlns="http://www.w3.org/1998/Math/MathML">
<apply>
<eq/>
<ci>E_Ks</ci>
<apply>
<times/>
<apply>
<divide/>
<apply>
<times/>
<ci>R</ci>
<ci>T</ci>
</apply>
<ci>F</ci>
</apply>
<apply>
<ln/>
<apply>
<divide/>
<apply>
<plus/>
<ci>K_o</ci>
<apply>
<times/>
<cn xmlns:cellml="http://www.cellml.org/cellml/1.0#" cellml:units="dimensionless">0.01833</cn>
<ci>Na_o</ci>
</apply>
</apply>
<apply>
<plus/>
<ci>K_i</ci>
<apply>
<times/>
<cn xmlns:cellml="http://www.cellml.org/cellml/1.0#" cellml:units="dimensionless">0.01833</cn>
<ci>Na_i</ci>
</apply>
</apply>
</apply>
</apply>
</apply>
</apply>
<apply>
<eq/>
<ci>i_Ks</ci>
<apply>
<times/>
<ci>g_Ks</ci>
<apply>
<power/>
<ci>X_ks</ci>
<cn xmlns:cellml="http://www.cellml.org/cellml/1.0#" cellml:units="dimensionless">2</cn>
</apply>
<apply>
<minus/>
<ci>V</ci>
<ci>E_Ks</ci>
</apply>
</apply>
</apply>
</math>
</component>
<component name="slow_activating_delayed_rectifiyer_K_current_X_ks_gate">
<variable initial_value="0.264" name="X_ks" public_interface="out" units="dimensionless"/>
<variable name="tau_X_ks" units="second"/>
<variable name="X_ks_infinity" units="dimensionless"/>
<variable name="V" public_interface="in" units="millivolt"/>
<variable name="time" public_interface="in" units="second"/>
<math xmlns="http://www.w3.org/1998/Math/MathML">
<apply>
<eq/>
<ci>X_ks_infinity</ci>
<apply>
<divide/>
<cn xmlns:cellml="http://www.cellml.org/cellml/1.0#" cellml:units="dimensionless">1</cn>
<apply>
<plus/>
<cn xmlns:cellml="http://www.cellml.org/cellml/1.0#" cellml:units="dimensionless">1</cn>
<apply>
<exp/>
<apply>
<divide/>
<apply>
<minus/>
<apply>
<minus/>
<ci>V</ci>
<cn xmlns:cellml="http://www.cellml.org/cellml/1.0#" cellml:units="millivolt">24.7</cn>
</apply>
</apply>
<cn xmlns:cellml="http://www.cellml.org/cellml/1.0#" cellml:units="millivolt">13.6</cn>
</apply>
</apply>
</apply>
</apply>
</apply>
<apply>
<eq/>
<ci>tau_X_ks</ci>
<apply>
<divide/>
<cn xmlns:cellml="http://www.cellml.org/cellml/1.0#" cellml:units="second">0.001</cn>
<apply>
<plus/>
<apply>
<divide/>
<apply>
<times/>
<cn xmlns:cellml="http://www.cellml.org/cellml/1.0#" cellml:units="per_millivolt">0.0000719</cn>
<apply>
<minus/>
<ci>V</ci>
<cn xmlns:cellml="http://www.cellml.org/cellml/1.0#" cellml:units="millivolt">10</cn>
</apply>
</apply>
<apply>
<minus/>
<cn xmlns:cellml="http://www.cellml.org/cellml/1.0#" cellml:units="dimensionless">1</cn>
<apply>
<exp/>
<apply>
<times/>
<apply>
<minus/>
<cn xmlns:cellml="http://www.cellml.org/cellml/1.0#" cellml:units="per_millivolt">0.148</cn>
</apply>
<apply>
<minus/>
<ci>V</ci>
<cn xmlns:cellml="http://www.cellml.org/cellml/1.0#" cellml:units="millivolt">10</cn>
</apply>
</apply>
</apply>
</apply>
</apply>
<apply>
<divide/>
<apply>
<times/>
<cn xmlns:cellml="http://www.cellml.org/cellml/1.0#" cellml:units="per_millivolt">0.000131</cn>
<apply>
<minus/>
<ci>V</ci>
<cn xmlns:cellml="http://www.cellml.org/cellml/1.0#" cellml:units="millivolt">10</cn>
</apply>
</apply>
<apply>
<minus/>
<apply>
<exp/>
<apply>
<times/>
<cn xmlns:cellml="http://www.cellml.org/cellml/1.0#" cellml:units="per_millivolt">0.0687</cn>
<apply>
<minus/>
<ci>V</ci>
<cn xmlns:cellml="http://www.cellml.org/cellml/1.0#" cellml:units="millivolt">10</cn>
</apply>
</apply>
</apply>
<cn xmlns:cellml="http://www.cellml.org/cellml/1.0#" cellml:units="dimensionless">1</cn>
</apply>
</apply>
</apply>
</apply>
</apply>
<apply>
<eq/>
<apply>
<diff/>
<bvar>
<ci>time</ci>
</bvar>
<ci>X_ks</ci>
</apply>
<apply>
<divide/>
<apply>
<minus/>
<ci>X_ks_infinity</ci>
<ci>X_ks</ci>
</apply>
<ci>tau_X_ks</ci>
</apply>
</apply>
</math>
</component>
<component name="transient_outward_potassium_current">
<variable cmeta:id="transient_outward_potassium_current_i_to1" name="i_to1" public_interface="out" units="microA_per_microF"/>
<variable initial_value="0.23815" name="g_to1" units="milliS_per_microF"/>
<variable name="time" private_interface="out" public_interface="in" units="second"/>
<variable name="V" private_interface="out" public_interface="in" units="millivolt"/>
<variable name="E_K" public_interface="in" units="millivolt"/>
<variable name="X_to1" private_interface="in" units="dimensionless"/>
<variable name="Y_to1" private_interface="in" units="dimensionless"/>
<math xmlns="http://www.w3.org/1998/Math/MathML">
<apply>
<eq/>
<ci>i_to1</ci>
<apply>
<times/>
<ci>g_to1</ci>
<ci>X_to1</ci>
<ci>Y_to1</ci>
<apply>
<minus/>
<ci>V</ci>
<ci>E_K</ci>
</apply>
</apply>
</apply>
</math>
</component>
<component name="transient_outward_potassium_current_X_to1_gate">
<variable initial_value="2.63" name="X_to1" public_interface="out" units="dimensionless"/>
<variable name="alpha_X_to1" units="per_second"/>
<variable name="beta_X_to1" units="per_second"/>
<variable name="V" public_interface="in" units="millivolt"/>
<variable name="time" public_interface="in" units="second"/>
<math xmlns="http://www.w3.org/1998/Math/MathML">
<apply>
<eq/>
<ci>alpha_X_to1</ci>
<apply>
<times/>
<cn xmlns:cellml="http://www.cellml.org/cellml/1.0#" cellml:units="per_second">45.16</cn>
<apply>
<exp/>
<apply>
<times/>
<cn xmlns:cellml="http://www.cellml.org/cellml/1.0#" cellml:units="per_millivolt">0.03577</cn>
<ci>V</ci>
</apply>
</apply>
</apply>
</apply>
<apply>
<eq/>
<ci>beta_X_to1</ci>
<apply>
<times/>
<cn xmlns:cellml="http://www.cellml.org/cellml/1.0#" cellml:units="per_second">98.9</cn>
<apply>
<exp/>
<apply>
<times/>
<apply>
<minus/>
<cn xmlns:cellml="http://www.cellml.org/cellml/1.0#" cellml:units="per_millivolt">0.06237</cn>
</apply>
<ci>V</ci>
</apply>
</apply>
</apply>
</apply>
<apply>
<eq/>
<apply>
<diff/>
<bvar>
<ci>time</ci>
</bvar>
<ci>X_to1</ci>
</apply>
<apply>
<minus/>
<apply>
<times/>
<ci>alpha_X_to1</ci>
<apply>
<minus/>
<cn xmlns:cellml="http://www.cellml.org/cellml/1.0#" cellml:units="dimensionless">1</cn>
<ci>X_to1</ci>
</apply>
</apply>
<apply>
<times/>
<ci>beta_X_to1</ci>
<ci>X_to1</ci>
</apply>
</apply>
</apply>
</math>
</component>
<component name="transient_outward_potassium_current_Y_to1_gate">
<variable initial_value="0.99" name="Y_to1" public_interface="out" units="dimensionless"/>
<variable name="alpha_Y_to1" units="per_second"/>
<variable name="beta_Y_to1" units="per_second"/>
<variable name="V" public_interface="in" units="millivolt"/>
<variable name="time" public_interface="in" units="second"/>
<math xmlns="http://www.w3.org/1998/Math/MathML">
<apply>
<eq/>
<ci>alpha_Y_to1</ci>
<apply>
<divide/>
<apply>
<times/>
<cn xmlns:cellml="http://www.cellml.org/cellml/1.0#" cellml:units="per_second">5.415</cn>
<apply>
<exp/>
<apply>
<divide/>
<apply>
<minus/>
<apply>
<plus/>
<ci>V</ci>
<cn xmlns:cellml="http://www.cellml.org/cellml/1.0#" cellml:units="millivolt">33.5</cn>
</apply>
</apply>
<cn xmlns:cellml="http://www.cellml.org/cellml/1.0#" cellml:units="millivolt">5</cn>
</apply>
</apply>
</apply>
<apply>
<plus/>
<cn xmlns:cellml="http://www.cellml.org/cellml/1.0#" cellml:units="dimensionless">1</cn>
<apply>
<times/>
<cn xmlns:cellml="http://www.cellml.org/cellml/1.0#" cellml:units="dimensionless">0.051335</cn>
<apply>
<exp/>
<apply>
<divide/>
<apply>
<minus/>
<apply>
<plus/>
<ci>V</ci>
<cn xmlns:cellml="http://www.cellml.org/cellml/1.0#" cellml:units="millivolt">33.5</cn>
</apply>
</apply>
<cn xmlns:cellml="http://www.cellml.org/cellml/1.0#" cellml:units="millivolt">5</cn>
</apply>
</apply>
</apply>
</apply>
</apply>
</apply>
<apply>
<eq/>
<ci>beta_Y_to1</ci>
<apply>
<divide/>
<apply>
<times/>
<cn xmlns:cellml="http://www.cellml.org/cellml/1.0#" cellml:units="per_second">5.415</cn>
<apply>
<exp/>
<apply>
<divide/>
<apply>
<plus/>
<ci>V</ci>
<cn xmlns:cellml="http://www.cellml.org/cellml/1.0#" cellml:units="millivolt">33.5</cn>
</apply>
<cn xmlns:cellml="http://www.cellml.org/cellml/1.0#" cellml:units="millivolt">5</cn>
</apply>
</apply>
</apply>
<apply>
<plus/>
<cn xmlns:cellml="http://www.cellml.org/cellml/1.0#" cellml:units="dimensionless">1</cn>
<apply>
<times/>
<cn xmlns:cellml="http://www.cellml.org/cellml/1.0#" cellml:units="dimensionless">0.051335</cn>
<apply>
<exp/>
<apply>
<divide/>
<apply>
<plus/>
<ci>V</ci>
<cn xmlns:cellml="http://www.cellml.org/cellml/1.0#" cellml:units="millivolt">33.5</cn>
</apply>
<cn xmlns:cellml="http://www.cellml.org/cellml/1.0#" cellml:units="millivolt">5</cn>
</apply>
</apply>
</apply>
</apply>
</apply>
</apply>
<apply>
<eq/>
<apply>
<diff/>
<bvar>
<ci>time</ci>
</bvar>
<ci>Y_to1</ci>
</apply>
<apply>
<minus/>
<apply>
<times/>
<ci>alpha_Y_to1</ci>
<apply>
<minus/>
<cn xmlns:cellml="http://www.cellml.org/cellml/1.0#" cellml:units="dimensionless">1</cn>
<ci>Y_to1</ci>
</apply>
</apply>
<apply>
<times/>
<ci>beta_Y_to1</ci>
<ci>Y_to1</ci>
</apply>
</apply>
</apply>
</math>
</component>
<component name="time_independent_potassium_current">
<variable cmeta:id="time_independent_potassium_current_i_K1" name="i_K1" public_interface="out" units="microA_per_microF"/>
<variable initial_value="2.8" name="g_K1" units="milliS_per_microF"/>
<variable initial_value="13" name="K_mK1" units="millimolar"/>
<variable name="time" private_interface="out" public_interface="in" units="second"/>
<variable name="V" private_interface="out" public_interface="in" units="millivolt"/>
<variable name="R" private_interface="out" public_interface="in" units="joule_per_mole_kelvin"/>
<variable name="T" private_interface="out" public_interface="in" units="kelvin"/>
<variable name="F" private_interface="out" public_interface="in" units="coulomb_per_millimole"/>
<variable name="E_K" private_interface="out" public_interface="in" units="millivolt"/>
<variable name="K_o" public_interface="in" units="millimolar"/>
<variable name="K1_infinity_V" private_interface="in" units="dimensionless"/>
<math xmlns="http://www.w3.org/1998/Math/MathML">
<apply>
<eq/>
<ci>i_K1</ci>
<apply>
<times/>
<apply>
<divide/>
<apply>
<times/>
<ci>g_K1</ci>
<ci>K1_infinity_V</ci>
<ci>K_o</ci>
</apply>
<apply>
<plus/>
<ci>K_o</ci>
<ci>K_mK1</ci>
</apply>
</apply>
<apply>
<minus/>
<ci>V</ci>
<ci>E_K</ci>
</apply>
</apply>
</apply>
</math>
</component>
<component name="time_independent_potassium_current_K1_gate">
<variable name="K1_infinity_V" public_interface="out" units="dimensionless"/>
<variable name="V" public_interface="in" units="millivolt"/>
<variable name="time" public_interface="in" units="second"/>
<variable name="E_K" public_interface="in" units="millivolt"/>
<variable name="R" public_interface="in" units="joule_per_mole_kelvin"/>
<variable name="T" public_interface="in" units="kelvin"/>
<variable name="F" public_interface="in" units="coulomb_per_millimole"/>
<math xmlns="http://www.w3.org/1998/Math/MathML">
<apply>
<eq/>
<ci>K1_infinity_V</ci>
<apply>
<divide/>
<cn xmlns:cellml="http://www.cellml.org/cellml/1.0#" cellml:units="dimensionless">1</cn>
<apply>
<plus/>
<cn xmlns:cellml="http://www.cellml.org/cellml/1.0#" cellml:units="dimensionless">2</cn>
<apply>
<exp/>
<apply>
<times/>
<apply>
<divide/>
<apply>
<times/>
<cn xmlns:cellml="http://www.cellml.org/cellml/1.0#" cellml:units="dimensionless">1.5</cn>
<ci>F</ci>
</apply>
<apply>
<times/>
<ci>R</ci>
<ci>T</ci>
</apply>
</apply>
<apply>
<minus/>
<ci>V</ci>
<ci>E_K</ci>
</apply>
</apply>
</apply>
</apply>
</apply>
</apply>
</math>
</component>
<component name="plateau_potassium_current">
<variable cmeta:id="plateau_potassium_current_i_Kp" name="i_Kp" public_interface="out" units="microA_per_microF"/>
<variable initial_value="0.002216" name="g_Kp" units="milliS_per_microF"/>
<variable name="time" private_interface="out" public_interface="in" units="second"/>
<variable name="V" private_interface="out" public_interface="in" units="millivolt"/>
<variable name="E_K" public_interface="in" units="millivolt"/>
<variable name="Kp_V" private_interface="in" units="dimensionless"/>
<math xmlns="http://www.w3.org/1998/Math/MathML">
<apply>
<eq/>
<ci>i_Kp</ci>
<apply>
<times/>
<ci>g_Kp</ci>
<ci>Kp_V</ci>
<apply>
<minus/>
<ci>V</ci>
<ci>E_K</ci>
</apply>
</apply>
</apply>
</math>
</component>
<component name="plateau_potassium_current_Kp_gate">
<variable name="Kp_V" public_interface="out" units="dimensionless"/>
<variable name="V" public_interface="in" units="millivolt"/>
<variable name="time" public_interface="in" units="second"/>
<math xmlns="http://www.w3.org/1998/Math/MathML">
<apply>
<eq/>
<ci>Kp_V</ci>
<apply>
<divide/>
<cn xmlns:cellml="http://www.cellml.org/cellml/1.0#" cellml:units="dimensionless">1</cn>
<apply>
<plus/>
<cn xmlns:cellml="http://www.cellml.org/cellml/1.0#" cellml:units="dimensionless">1</cn>
<apply>
<exp/>
<apply>
<divide/>
<apply>
<minus/>
<cn xmlns:cellml="http://www.cellml.org/cellml/1.0#" cellml:units="millivolt">7.488</cn>
<ci>V</ci>
</apply>
<cn xmlns:cellml="http://www.cellml.org/cellml/1.0#" cellml:units="millivolt">5.98</cn>
</apply>
</apply>
</apply>
</apply>
</apply>
</math>
</component>
<component name="Na_Ca_exchanger">
<variable cmeta:id="Na_Ca_exchanger_i_NaCa" name="i_NaCa" public_interface="out" units="microA_per_microF"/>
<variable initial_value="1.38" name="K_mCa" units="millimolar"/>
<variable initial_value="87.5" name="K_mNa" units="millimolar"/>
<variable initial_value="0.3" name="K_NaCa" units="microA_per_microF"/>
<variable initial_value="0.2" name="K_sat" units="dimensionless"/>
<variable initial_value="0.35" name="eta" units="dimensionless"/>
<variable name="time" public_interface="in" units="second"/>
<variable name="V" public_interface="in" units="millivolt"/>
<variable name="R" public_interface="in" units="joule_per_mole_kelvin"/>
<variable name="T" public_interface="in" units="kelvin"/>
<variable name="F" public_interface="in" units="coulomb_per_millimole"/>
<variable name="Na_i" public_interface="in" units="millimolar"/>
<variable name="Na_o" public_interface="in" units="millimolar"/>
<variable name="Ca_i" public_interface="in" units="millimolar"/>
<variable name="Ca_o" public_interface="in" units="millimolar"/>
<math xmlns="http://www.w3.org/1998/Math/MathML">
<apply>
<eq/>
<ci>i_NaCa</ci>
<apply>
<times/>
<apply>
<divide/>
<apply>
<times/>
<ci>K_NaCa</ci>
<cn xmlns:cellml="http://www.cellml.org/cellml/1.0#" cellml:units="dimensionless">5000</cn>
</apply>
<apply>
<times/>
<apply>
<plus/>
<apply>
<power/>
<ci>K_mNa</ci>
<cn xmlns:cellml="http://www.cellml.org/cellml/1.0#" cellml:units="dimensionless">3</cn>
</apply>
<apply>
<power/>
<ci>Na_o</ci>
<cn xmlns:cellml="http://www.cellml.org/cellml/1.0#" cellml:units="dimensionless">3</cn>
</apply>
</apply>
<apply>
<plus/>
<ci>K_mCa</ci>
<ci>Ca_o</ci>
</apply>
<apply>
<plus/>
<cn xmlns:cellml="http://www.cellml.org/cellml/1.0#" cellml:units="dimensionless">1</cn>
<apply>
<times/>
<ci>K_sat</ci>
<apply>
<exp/>
<apply>
<divide/>
<apply>
<times/>
<apply>
<minus/>
<ci>eta</ci>
<cn xmlns:cellml="http://www.cellml.org/cellml/1.0#" cellml:units="dimensionless">1</cn>
</apply>
<ci>V</ci>
<ci>F</ci>
</apply>
<apply>
<times/>
<ci>R</ci>
<ci>T</ci>
</apply>
</apply>
</apply>
</apply>
</apply>
</apply>
</apply>
<apply>
<minus/>
<apply>
<times/>
<apply>
<exp/>
<apply>
<divide/>
<apply>
<times/>
<ci>eta</ci>
<ci>V</ci>
<ci>F</ci>
</apply>
<apply>
<times/>
<ci>R</ci>
<ci>T</ci>
</apply>
</apply>
</apply>
<apply>
<power/>
<ci>Na_i</ci>
<cn xmlns:cellml="http://www.cellml.org/cellml/1.0#" cellml:units="dimensionless">3</cn>
</apply>
<ci>Ca_o</ci>
</apply>
<apply>
<times/>
<apply>
<exp/>
<apply>
<divide/>
<apply>
<times/>
<apply>
<minus/>
<ci>eta</ci>
<cn xmlns:cellml="http://www.cellml.org/cellml/1.0#" cellml:units="dimensionless">1</cn>
</apply>
<ci>V</ci>
<ci>F</ci>
</apply>
<apply>
<times/>
<ci>R</ci>
<ci>T</ci>
</apply>
</apply>
</apply>
<apply>
<power/>
<ci>Na_o</ci>
<cn xmlns:cellml="http://www.cellml.org/cellml/1.0#" cellml:units="dimensionless">3</cn>
</apply>
<ci>Ca_i</ci>
</apply>
</apply>
</apply>
</apply>
</math>
</component>
<component name="sodium_potassium_pump">
<variable cmeta:id="sodium_potassium_pump_i_NaK" name="i_NaK" public_interface="out" units="microA_per_microF"/>
<variable name="i_NaK_winslow" units="microA_per_microF"/>
<variable initial_value="0.693" name="I_NaK" units="microA_per_microF"/>
<variable name="f_NaK" units="dimensionless"/>
<variable initial_value="10" name="K_mNa_i" units="millimolar"/>
<variable initial_value="1.5" name="K_mK_o" units="millimolar"/>
<variable name="sigma" units="dimensionless"/>
<variable name="time" public_interface="in" units="second"/>
<variable name="V" public_interface="in" units="millivolt"/>
<variable name="R" public_interface="in" units="joule_per_mole_kelvin"/>
<variable name="T" public_interface="in" units="kelvin"/>
<variable name="F" public_interface="in" units="coulomb_per_millimole"/>
<variable name="Na_i" public_interface="in" units="millimolar"/>
<variable name="Na_o" public_interface="in" units="millimolar"/>
<variable name="K_o" public_interface="in" units="millimolar"/>
<variable name="MgATP_i" public_interface="in" units="millimolar"/>
<variable name="MgATP_i0" public_interface="in" units="millimolar"/>
<math xmlns="http://www.w3.org/1998/Math/MathML">
<apply>
<eq/>
<ci>f_NaK</ci>
<apply>
<divide/>
<cn xmlns:cellml="http://www.cellml.org/cellml/1.0#" cellml:units="dimensionless">1</cn>
<apply>
<plus/>
<cn xmlns:cellml="http://www.cellml.org/cellml/1.0#" cellml:units="dimensionless">1</cn>
<apply>
<times/>
<cn xmlns:cellml="http://www.cellml.org/cellml/1.0#" cellml:units="dimensionless">0.1245</cn>
<apply>
<exp/>
<apply>
<divide/>
<apply>
<times/>
<apply>
<minus/>
<cn xmlns:cellml="http://www.cellml.org/cellml/1.0#" cellml:units="dimensionless">0.1</cn>
</apply>
<ci>V</ci>
<ci>F</ci>
</apply>
<apply>
<times/>
<ci>R</ci>
<ci>T</ci>
</apply>
</apply>
</apply>
</apply>
<apply>
<times/>
<cn xmlns:cellml="http://www.cellml.org/cellml/1.0#" cellml:units="dimensionless">0.0365</cn>
<ci>sigma</ci>
<apply>
<exp/>
<apply>
<divide/>
<apply>
<times/>
<apply>
<minus/>
<ci>V</ci>
</apply>
<ci>F</ci>
</apply>
<apply>
<times/>
<ci>R</ci>
<ci>T</ci>
</apply>
</apply>
</apply>
</apply>
</apply>
</apply>
</apply>
<apply>
<eq/>
<ci>sigma</ci>
<apply>
<times/>
<apply>
<divide/>
<cn xmlns:cellml="http://www.cellml.org/cellml/1.0#" cellml:units="dimensionless">1</cn>
<cn xmlns:cellml="http://www.cellml.org/cellml/1.0#" cellml:units="dimensionless">7</cn>
</apply>
<apply>
<minus/>
<apply>
<exp/>
<apply>
<divide/>
<ci>Na_o</ci>
<cn xmlns:cellml="http://www.cellml.org/cellml/1.0#" cellml:units="millimolar">67.3</cn>
</apply>
</apply>
<cn xmlns:cellml="http://www.cellml.org/cellml/1.0#" cellml:units="dimensionless">1</cn>
</apply>
</apply>
</apply>
<apply>
<eq/>
<ci>i_NaK</ci>
<apply>
<times/>
<apply>
<divide/>
<ci>MgATP_i</ci>
<ci>MgATP_i0</ci>
</apply>
<ci>i_NaK_winslow</ci>
</apply>
</apply>
<apply>
<eq/>
<ci>i_NaK_winslow</ci>
<apply>
<divide/>
<apply>
<times/>
<apply>
<divide/>
<apply>
<times/>
<ci>I_NaK</ci>
<ci>f_NaK</ci>
</apply>
<apply>
<plus/>
<cn xmlns:cellml="http://www.cellml.org/cellml/1.0#" cellml:units="dimensionless">1</cn>
<apply>
<power/>
<apply>
<divide/>
<ci>K_mNa_i</ci>
<ci>Na_i</ci>
</apply>
<cn xmlns:cellml="http://www.cellml.org/cellml/1.0#" cellml:units="dimensionless">1.5</cn>
</apply>
</apply>
</apply>
<ci>K_o</ci>
</apply>
<apply>
<plus/>
<ci>K_o</ci>
<ci>K_mK_o</ci>
</apply>
</apply>
</apply>
</math>
</component>
<component name="sarcolemmal_calcium_pump">
<variable cmeta:id="sarcolemmal_calcium_pump_i_p_Ca" name="i_p_Ca" public_interface="out" units="microA_per_microF"/>
<variable name="i_p_Ca_winslow" units="microA_per_microF"/>
<variable initial_value="0.00005" name="K_mpCa" units="millimolar"/>
<variable initial_value="0.05" name="I_pCa" units="microA_per_microF"/>
<variable name="time" public_interface="in" units="second"/>
<variable name="Ca_i" public_interface="in" units="millimolar"/>
<variable name="MgATP_i" public_interface="in" units="millimolar"/>
<variable name="MgATP_i0" public_interface="in" units="millimolar"/>
<math xmlns="http://www.w3.org/1998/Math/MathML">
<apply>
<eq/>
<ci>i_p_Ca</ci>
<apply>
<times/>
<apply>
<divide/>
<ci>MgATP_i</ci>
<ci>MgATP_i0</ci>
</apply>
<ci>i_p_Ca_winslow</ci>
</apply>
</apply>
<apply>
<eq/>
<ci>i_p_Ca_winslow</ci>
<apply>
<divide/>
<apply>
<times/>
<ci>I_pCa</ci>
<ci>Ca_i</ci>
</apply>
<apply>
<plus/>
<ci>K_mpCa</ci>
<ci>Ca_i</ci>
</apply>
</apply>
</apply>
</math>
</component>
<component name="calcium_background_current">
<variable cmeta:id="calcium_background_current_i_Ca_b" name="i_Ca_b" public_interface="out" units="microA_per_microF"/>
<variable initial_value="0.0003842" name="g_Cab" units="milliS_per_microF"/>
<variable name="E_Ca" units="millivolt"/>
<variable name="time" public_interface="in" units="second"/>
<variable name="V" public_interface="in" units="millivolt"/>
<variable name="R" public_interface="in" units="joule_per_mole_kelvin"/>
<variable name="T" public_interface="in" units="kelvin"/>
<variable name="F" public_interface="in" units="coulomb_per_millimole"/>
<variable name="Ca_i" public_interface="in" units="millimolar"/>
<variable name="Ca_o" public_interface="in" units="millimolar"/>
<math xmlns="http://www.w3.org/1998/Math/MathML">
<apply>
<eq/>
<ci>E_Ca</ci>
<apply>
<times/>
<apply>
<divide/>
<apply>
<times/>
<ci>R</ci>
<ci>T</ci>
</apply>
<apply>
<times/>
<cn xmlns:cellml="http://www.cellml.org/cellml/1.0#" cellml:units="dimensionless">2</cn>
<ci>F</ci>
</apply>
</apply>
<apply>
<ln/>
<apply>
<divide/>
<ci>Ca_o</ci>
<ci>Ca_i</ci>
</apply>
</apply>
</apply>
</apply>
<apply>
<eq/>
<ci>i_Ca_b</ci>
<apply>
<times/>
<ci>g_Cab</ci>
<apply>
<minus/>
<ci>V</ci>
<ci>E_Ca</ci>
</apply>
</apply>
</apply>
</math>
</component>
<component name="sodium_background_current">
<variable cmeta:id="sodium_background_current_i_Na_b" name="i_Na_b" public_interface="out" units="microA_per_microF"/>
<variable initial_value="0.0031" name="g_Nab" units="milliS_per_microF"/>
<variable name="time" public_interface="in" units="second"/>
<variable name="V" public_interface="in" units="millivolt"/>
<variable name="E_Na" public_interface="in" units="millivolt"/>
<math xmlns="http://www.w3.org/1998/Math/MathML">
<apply>
<eq/>
<ci>i_Na_b</ci>
<apply>
<times/>
<ci>g_Nab</ci>
<apply>
<minus/>
<ci>V</ci>
<ci>E_Na</ci>
</apply>
</apply>
</apply>
</math>
</component>
<component name="L_type_Ca_current">
<variable cmeta:id="L_type_Ca_current_i_Ca" name="i_Ca" public_interface="out" units="microA_per_microF"/>
<variable cmeta:id="L_type_Ca_current_i_Ca_K" name="i_Ca_K" public_interface="out" units="microA_per_microF"/>
<variable initial_value="3.125e-4" name="P_Ca" units="cm_per_second"/>
<variable initial_value="5.79e-7" name="P_K" units="cm_per_second"/>
<variable name="p_prime_k" units="cm_per_second"/>
<variable initial_value="-0.265" name="i_Ca_half" units="microA_per_microF"/>
<variable name="i_Ca_max" units="microA_per_microF"/>
<variable initial_value="9.84546e-21" name="O" units="dimensionless"/>
<variable initial_value="0" name="O_Ca" units="dimensionless"/>
<variable name="alpha" units="per_second"/>
<variable name="beta" units="per_second"/>
<variable name="gamma" units="per_second"/>
<variable name="alpha_a" units="per_second"/>
<variable name="beta_b" units="per_second"/>
<variable initial_value="2" name="a" units="dimensionless"/>
<variable initial_value="2" name="b" units="dimensionless"/>
<variable initial_value="2000" name="g" units="per_second"/>
<variable initial_value="300" name="f" units="per_second"/>
<variable initial_value="7000" name="gprime" units="per_second"/>
<variable initial_value="7" name="fprime" units="per_second"/>
<variable initial_value="10" name="omega" units="per_second"/>
<variable initial_value="0.997208" name="C0" units="dimensionless"/>
<variable initial_value="6.38897e-5" name="C1" units="dimensionless"/>
<variable initial_value="1.535e-9" name="C2" units="dimensionless"/>
<variable initial_value="1.63909e-14" name="C3" units="dimensionless"/>
<variable initial_value="6.56337e-20" name="C4" units="dimensionless"/>
<variable initial_value="0.00272826" name="C_Ca0" units="dimensionless"/>
<variable initial_value="6.99215e-7" name="C_Ca1" units="dimensionless"/>
<variable initial_value="6.71989e-11" name="C_Ca2" units="dimensionless"/>
<variable initial_value="2.87031e-15" name="C_Ca3" units="dimensionless"/>
<variable initial_value="4.59752e-20" name="C_Ca4" units="dimensionless"/>
<variable name="time" private_interface="out" public_interface="in" units="second"/>
<variable name="V" private_interface="out" public_interface="in" units="millivolt"/>
<variable name="C_sc" public_interface="in" units="microF_per_cm2"/>
<variable name="Ca_ss" public_interface="in" units="millimolar"/>
<variable name="Ca_o" public_interface="in" units="millimolar"/>
<variable name="K_o" public_interface="in" units="millimolar"/>
<variable name="K_i" public_interface="in" units="millimolar"/>
<variable name="R" public_interface="in" units="joule_per_mole_kelvin"/>
<variable name="T" public_interface="in" units="kelvin"/>
<variable name="F" public_interface="in" units="coulomb_per_millimole"/>
<variable name="y" private_interface="in" units="dimensionless"/>
<math xmlns="http://www.w3.org/1998/Math/MathML">
<apply>
<eq/>
<ci>i_Ca</ci>
<apply>
<times/>
<ci>i_Ca_max</ci>
<ci>y</ci>
<apply>
<plus/>
<ci>O</ci>
<ci>O_Ca</ci>
</apply>
</apply>
</apply>
<apply>
<eq/>
<ci>i_Ca_K</ci>
<apply>
<divide/>
<apply>
<times/>
<apply>
<divide/>
<apply>
<times/>
<apply>
<divide/>
<ci>p_prime_k</ci>
<apply>
<times/>
<cn xmlns:cellml="http://www.cellml.org/cellml/1.0#" cellml:units="microF_per_cm2">1</cn>
<cn xmlns:cellml="http://www.cellml.org/cellml/1.0#" cellml:units="second_per_millisecond">1</cn>
</apply>
</apply>
<ci>y</ci>
<apply>
<plus/>
<ci>O</ci>
<ci>O_Ca</ci>
</apply>
<ci>V</ci>
<apply>
<power/>
<ci>F</ci>
<cn xmlns:cellml="http://www.cellml.org/cellml/1.0#" cellml:units="dimensionless">2</cn>
</apply>
</apply>
<apply>
<times/>
<ci>R</ci>
<ci>T</ci>
</apply>
</apply>
<apply>
<minus/>
<apply>
<times/>
<ci>K_i</ci>
<apply>
<exp/>
<apply>
<divide/>
<apply>
<times/>
<ci>V</ci>
<ci>F</ci>
</apply>
<apply>
<times/>
<ci>R</ci>
<ci>T</ci>
</apply>
</apply>
</apply>
</apply>
<ci>K_o</ci>
</apply>
</apply>
<apply>
<minus/>
<apply>
<exp/>
<apply>
<divide/>
<apply>
<times/>
<ci>V</ci>
<ci>F</ci>
</apply>
<apply>
<times/>
<ci>R</ci>
<ci>T</ci>
</apply>
</apply>
</apply>
<cn xmlns:cellml="http://www.cellml.org/cellml/1.0#" cellml:units="dimensionless">1</cn>
</apply>
</apply>
</apply>
<apply>
<eq/>
<ci>p_prime_k</ci>
<apply>
<divide/>
<ci>P_K</ci>
<apply>
<plus/>
<cn xmlns:cellml="http://www.cellml.org/cellml/1.0#" cellml:units="dimensionless">1</cn>
<apply>
<divide/>
<ci>i_Ca_max</ci>
<ci>i_Ca_half</ci>
</apply>
</apply>
</apply>
</apply>
<apply>
<eq/>
<ci>i_Ca_max</ci>
<apply>
<divide/>
<apply>
<times/>
<apply>
<divide/>
<apply>
<times/>
<apply>
<divide/>
<ci>P_Ca</ci>
<apply>
<times/>
<cn xmlns:cellml="http://www.cellml.org/cellml/1.0#" cellml:units="microF_per_cm2">1</cn>
<cn xmlns:cellml="http://www.cellml.org/cellml/1.0#" cellml:units="second_per_millisecond">1</cn>
</apply>
</apply>
<cn xmlns:cellml="http://www.cellml.org/cellml/1.0#" cellml:units="dimensionless">4</cn>
<ci>V</ci>
<apply>
<power/>
<ci>F</ci>
<cn xmlns:cellml="http://www.cellml.org/cellml/1.0#" cellml:units="dimensionless">2</cn>
</apply>
<cn xmlns:cellml="http://www.cellml.org/cellml/1.0#" cellml:units="dimensionless">1000</cn>
</apply>
<apply>
<times/>
<ci>R</ci>
<ci>T</ci>
</apply>
</apply>
<apply>
<minus/>
<apply>
<times/>
<cn xmlns:cellml="http://www.cellml.org/cellml/1.0#" cellml:units="millimolar">0.001</cn>
<apply>
<exp/>
<apply>
<divide/>
<apply>
<times/>
<cn xmlns:cellml="http://www.cellml.org/cellml/1.0#" cellml:units="dimensionless">2</cn>
<ci>V</ci>
<ci>F</ci>
</apply>
<apply>
<times/>
<ci>R</ci>
<ci>T</ci>
</apply>
</apply>
</apply>
</apply>
<apply>
<times/>
<cn xmlns:cellml="http://www.cellml.org/cellml/1.0#" cellml:units="dimensionless">0.341</cn>
<ci>Ca_o</ci>
</apply>
</apply>
</apply>
<apply>
<minus/>
<apply>
<exp/>
<apply>
<divide/>
<apply>
<times/>
<cn xmlns:cellml="http://www.cellml.org/cellml/1.0#" cellml:units="dimensionless">2</cn>
<ci>V</ci>
<ci>F</ci>
</apply>
<apply>
<times/>
<ci>R</ci>
<ci>T</ci>
</apply>
</apply>
</apply>
<cn xmlns:cellml="http://www.cellml.org/cellml/1.0#" cellml:units="dimensionless">1</cn>
</apply>
</apply>
</apply>
<apply>
<eq/>
<ci>alpha</ci>
<apply>
<times/>
<cn xmlns:cellml="http://www.cellml.org/cellml/1.0#" cellml:units="per_second">400</cn>
<apply>
<exp/>
<apply>
<divide/>
<apply>
<plus/>
<ci>V</ci>
<cn xmlns:cellml="http://www.cellml.org/cellml/1.0#" cellml:units="millivolt">2</cn>
</apply>
<cn xmlns:cellml="http://www.cellml.org/cellml/1.0#" cellml:units="millivolt">10</cn>
</apply>
</apply>
</apply>
</apply>
<apply>
<eq/>
<ci>beta</ci>
<apply>
<times/>
<cn xmlns:cellml="http://www.cellml.org/cellml/1.0#" cellml:units="per_second">50</cn>
<apply>
<exp/>
<apply>
<divide/>
<apply>
<minus/>
<apply>
<plus/>
<ci>V</ci>
<cn xmlns:cellml="http://www.cellml.org/cellml/1.0#" cellml:units="millivolt">2</cn>
</apply>
</apply>
<cn xmlns:cellml="http://www.cellml.org/cellml/1.0#" cellml:units="millivolt">13</cn>
</apply>
</apply>
</apply>
</apply>
<apply>
<eq/>
<ci>alpha_a</ci>
<apply>
<times/>
<ci>alpha</ci>
<ci>a</ci>
</apply>
</apply>
<apply>
<eq/>
<ci>beta_b</ci>
<apply>
<divide/>
<ci>beta</ci>
<ci>b</ci>
</apply>
</apply>
<apply>
<eq/>
<ci>gamma</ci>
<apply>
<divide/>
<apply>
<times/>
<cn xmlns:cellml="http://www.cellml.org/cellml/1.0#" cellml:units="per_second">103.75</cn>
<ci>Ca_ss</ci>
</apply>
<cn xmlns:cellml="http://www.cellml.org/cellml/1.0#" cellml:units="millimolar">1</cn>
</apply>
</apply>
<apply>
<eq/>
<apply>
<diff/>
<bvar>
<ci>time</ci>
</bvar>
<ci>C0</ci>
</apply>
<apply>
<minus/>
<apply>
<plus/>
<apply>
<times/>
<ci>beta</ci>
<ci>C1</ci>
</apply>
<apply>
<times/>
<ci>omega</ci>
<ci>C_Ca0</ci>
</apply>
</apply>
<apply>
<times/>
<apply>
<plus/>
<apply>
<times/>
<cn xmlns:cellml="http://www.cellml.org/cellml/1.0#" cellml:units="dimensionless">4</cn>
<ci>alpha</ci>
</apply>
<ci>gamma</ci>
</apply>
<ci>C0</ci>
</apply>
</apply>
</apply>
<apply>
<eq/>
<apply>
<diff/>
<bvar>
<ci>time</ci>
</bvar>
<ci>C1</ci>
</apply>
<apply>
<minus/>
<apply>
<plus/>
<apply>
<times/>
<cn xmlns:cellml="http://www.cellml.org/cellml/1.0#" cellml:units="dimensionless">4</cn>
<ci>alpha</ci>
<ci>C0</ci>
</apply>
<apply>
<times/>
<cn xmlns:cellml="http://www.cellml.org/cellml/1.0#" cellml:units="dimensionless">2</cn>
<ci>beta</ci>
<ci>C2</ci>
</apply>
<apply>
<times/>
<apply>
<divide/>
<ci>omega</ci>
<ci>b</ci>
</apply>
<ci>C_Ca1</ci>
</apply>
</apply>
<apply>
<times/>
<apply>
<plus/>
<ci>beta</ci>
<apply>
<times/>
<cn xmlns:cellml="http://www.cellml.org/cellml/1.0#" cellml:units="dimensionless">3</cn>
<ci>alpha</ci>
</apply>
<apply>
<times/>
<ci>gamma</ci>
<ci>a</ci>
</apply>
</apply>
<ci>C1</ci>
</apply>
</apply>
</apply>
<apply>
<eq/>
<apply>
<diff/>
<bvar>
<ci>time</ci>
</bvar>
<ci>C2</ci>
</apply>
<apply>
<minus/>
<apply>
<plus/>
<apply>
<times/>
<cn xmlns:cellml="http://www.cellml.org/cellml/1.0#" cellml:units="dimensionless">3</cn>
<ci>alpha</ci>
<ci>C1</ci>
</apply>
<apply>
<times/>
<cn xmlns:cellml="http://www.cellml.org/cellml/1.0#" cellml:units="dimensionless">3</cn>
<ci>beta</ci>
<ci>C3</ci>
</apply>
<apply>
<times/>
<apply>
<divide/>
<ci>omega</ci>
<apply>
<power/>
<ci>b</ci>
<cn xmlns:cellml="http://www.cellml.org/cellml/1.0#" cellml:units="dimensionless">2</cn>
</apply>
</apply>
<ci>C_Ca2</ci>
</apply>
</apply>
<apply>
<times/>
<apply>
<plus/>
<apply>
<times/>
<ci>beta</ci>
<cn xmlns:cellml="http://www.cellml.org/cellml/1.0#" cellml:units="dimensionless">2</cn>
</apply>
<apply>
<times/>
<cn xmlns:cellml="http://www.cellml.org/cellml/1.0#" cellml:units="dimensionless">2</cn>
<ci>alpha</ci>
</apply>
<apply>
<times/>
<ci>gamma</ci>
<apply>
<power/>
<ci>a</ci>
<cn xmlns:cellml="http://www.cellml.org/cellml/1.0#" cellml:units="dimensionless">2</cn>
</apply>
</apply>
</apply>
<ci>C2</ci>
</apply>
</apply>
</apply>
<apply>
<eq/>
<apply>
<diff/>
<bvar>
<ci>time</ci>
</bvar>
<ci>C3</ci>
</apply>
<apply>
<minus/>
<apply>
<plus/>
<apply>
<times/>
<cn xmlns:cellml="http://www.cellml.org/cellml/1.0#" cellml:units="dimensionless">2</cn>
<ci>alpha</ci>
<ci>C2</ci>
</apply>
<apply>
<times/>
<cn xmlns:cellml="http://www.cellml.org/cellml/1.0#" cellml:units="dimensionless">4</cn>
<ci>beta</ci>
<ci>C4</ci>
</apply>
<apply>
<times/>
<apply>
<divide/>
<ci>omega</ci>
<apply>
<power/>
<ci>b</ci>
<cn xmlns:cellml="http://www.cellml.org/cellml/1.0#" cellml:units="dimensionless">3</cn>
</apply>
</apply>
<ci>C_Ca3</ci>
</apply>
</apply>
<apply>
<times/>
<apply>
<plus/>
<apply>
<times/>
<ci>beta</ci>
<cn xmlns:cellml="http://www.cellml.org/cellml/1.0#" cellml:units="dimensionless">3</cn>
</apply>
<ci>alpha</ci>
<apply>
<times/>
<ci>gamma</ci>
<apply>
<power/>
<ci>a</ci>
<cn xmlns:cellml="http://www.cellml.org/cellml/1.0#" cellml:units="dimensionless">3</cn>
</apply>
</apply>
</apply>
<ci>C3</ci>
</apply>
</apply>
</apply>
<apply>
<eq/>
<apply>
<diff/>
<bvar>
<ci>time</ci>
</bvar>
<ci>C4</ci>
</apply>
<apply>
<minus/>
<apply>
<plus/>
<apply>
<times/>
<ci>alpha</ci>
<ci>C3</ci>
</apply>
<apply>
<times/>
<ci>g</ci>
<ci>O</ci>
</apply>
<apply>
<times/>
<apply>
<divide/>
<ci>omega</ci>
<apply>
<power/>
<ci>b</ci>
<cn xmlns:cellml="http://www.cellml.org/cellml/1.0#" cellml:units="dimensionless">4</cn>
</apply>
</apply>
<ci>C_Ca4</ci>
</apply>
</apply>
<apply>
<times/>
<apply>
<plus/>
<apply>
<times/>
<ci>beta</ci>
<cn xmlns:cellml="http://www.cellml.org/cellml/1.0#" cellml:units="dimensionless">4</cn>
</apply>
<ci>f</ci>
<apply>
<times/>
<ci>gamma</ci>
<apply>
<power/>
<ci>a</ci>
<cn xmlns:cellml="http://www.cellml.org/cellml/1.0#" cellml:units="dimensionless">4</cn>
</apply>
</apply>
</apply>
<ci>C4</ci>
</apply>
</apply>
</apply>
<apply>
<eq/>
<apply>
<diff/>
<bvar>
<ci>time</ci>
</bvar>
<ci>O</ci>
</apply>
<apply>
<minus/>
<apply>
<times/>
<ci>f</ci>
<ci>C4</ci>
</apply>
<apply>
<times/>
<ci>g</ci>
<ci>O</ci>
</apply>
</apply>
</apply>
<apply>
<eq/>
<apply>
<diff/>
<bvar>
<ci>time</ci>
</bvar>
<ci>C_Ca0</ci>
</apply>
<apply>
<minus/>
<apply>
<plus/>
<apply>
<times/>
<ci>beta_b</ci>
<ci>C_Ca1</ci>
</apply>
<apply>
<times/>
<ci>gamma</ci>
<ci>C0</ci>
</apply>
</apply>
<apply>
<times/>
<apply>
<plus/>
<apply>
<times/>
<cn xmlns:cellml="http://www.cellml.org/cellml/1.0#" cellml:units="dimensionless">4</cn>
<ci>alpha_a</ci>
</apply>
<ci>omega</ci>
</apply>
<ci>C_Ca0</ci>
</apply>
</apply>
</apply>
<apply>
<eq/>
<apply>
<diff/>
<bvar>
<ci>time</ci>
</bvar>
<ci>C_Ca1</ci>
</apply>
<apply>
<minus/>
<apply>
<plus/>
<apply>
<times/>
<cn xmlns:cellml="http://www.cellml.org/cellml/1.0#" cellml:units="dimensionless">4</cn>
<ci>alpha_a</ci>
<ci>C_Ca0</ci>
</apply>
<apply>
<times/>
<cn xmlns:cellml="http://www.cellml.org/cellml/1.0#" cellml:units="dimensionless">2</cn>
<ci>beta_b</ci>
<ci>C_Ca2</ci>
</apply>
<apply>
<times/>
<ci>gamma</ci>
<ci>a</ci>
<ci>C1</ci>
</apply>
</apply>
<apply>
<times/>
<apply>
<plus/>
<ci>beta_b</ci>
<apply>
<times/>
<cn xmlns:cellml="http://www.cellml.org/cellml/1.0#" cellml:units="dimensionless">3</cn>
<ci>alpha_a</ci>
</apply>
<apply>
<divide/>
<ci>omega</ci>
<ci>b</ci>
</apply>
</apply>
<ci>C_Ca1</ci>
</apply>
</apply>
</apply>
<apply>
<eq/>
<apply>
<diff/>
<bvar>
<ci>time</ci>
</bvar>
<ci>C_Ca2</ci>
</apply>
<apply>
<minus/>
<apply>
<plus/>
<apply>
<times/>
<cn xmlns:cellml="http://www.cellml.org/cellml/1.0#" cellml:units="dimensionless">3</cn>
<ci>alpha_a</ci>
<ci>C_Ca1</ci>
</apply>
<apply>
<times/>
<cn xmlns:cellml="http://www.cellml.org/cellml/1.0#" cellml:units="dimensionless">3</cn>
<ci>beta_b</ci>
<ci>C_Ca3</ci>
</apply>
<apply>
<times/>
<ci>gamma</ci>
<apply>
<power/>
<ci>a</ci>
<cn xmlns:cellml="http://www.cellml.org/cellml/1.0#" cellml:units="dimensionless">2</cn>
</apply>
<ci>C2</ci>
</apply>
</apply>
<apply>
<times/>
<apply>
<plus/>
<apply>
<times/>
<ci>beta_b</ci>
<cn xmlns:cellml="http://www.cellml.org/cellml/1.0#" cellml:units="dimensionless">2</cn>
</apply>
<apply>
<times/>
<cn xmlns:cellml="http://www.cellml.org/cellml/1.0#" cellml:units="dimensionless">2</cn>
<ci>alpha_a</ci>
</apply>
<apply>
<divide/>
<ci>omega</ci>
<apply>
<power/>
<ci>b</ci>
<cn xmlns:cellml="http://www.cellml.org/cellml/1.0#" cellml:units="dimensionless">2</cn>
</apply>
</apply>
</apply>
<ci>C_Ca2</ci>
</apply>
</apply>
</apply>
<apply>
<eq/>
<apply>
<diff/>
<bvar>
<ci>time</ci>
</bvar>
<ci>C_Ca3</ci>
</apply>
<apply>
<minus/>
<apply>
<plus/>
<apply>
<times/>
<cn xmlns:cellml="http://www.cellml.org/cellml/1.0#" cellml:units="dimensionless">2</cn>
<ci>alpha_a</ci>
<ci>C_Ca2</ci>
</apply>
<apply>
<times/>
<cn xmlns:cellml="http://www.cellml.org/cellml/1.0#" cellml:units="dimensionless">4</cn>
<ci>beta_b</ci>
<ci>C_Ca4</ci>
</apply>
<apply>
<times/>
<ci>gamma</ci>
<apply>
<power/>
<ci>a</ci>
<cn xmlns:cellml="http://www.cellml.org/cellml/1.0#" cellml:units="dimensionless">3</cn>
</apply>
<ci>C3</ci>
</apply>
</apply>
<apply>
<times/>
<apply>
<plus/>
<apply>
<times/>
<ci>beta_b</ci>
<cn xmlns:cellml="http://www.cellml.org/cellml/1.0#" cellml:units="dimensionless">3</cn>
</apply>
<ci>alpha_a</ci>
<apply>
<divide/>
<ci>omega</ci>
<apply>
<power/>
<ci>b</ci>
<cn xmlns:cellml="http://www.cellml.org/cellml/1.0#" cellml:units="dimensionless">3</cn>
</apply>
</apply>
</apply>
<ci>C_Ca3</ci>
</apply>
</apply>
</apply>
<apply>
<eq/>
<apply>
<diff/>
<bvar>
<ci>time</ci>
</bvar>
<ci>C_Ca4</ci>
</apply>
<apply>
<minus/>
<apply>
<plus/>
<apply>
<times/>
<ci>alpha_a</ci>
<ci>C_Ca3</ci>
</apply>
<apply>
<times/>
<ci>gprime</ci>
<ci>O_Ca</ci>
</apply>
<apply>
<times/>
<ci>gamma</ci>
<apply>
<power/>
<ci>a</ci>
<cn xmlns:cellml="http://www.cellml.org/cellml/1.0#" cellml:units="dimensionless">4</cn>
</apply>
<ci>C4</ci>
</apply>
</apply>
<apply>
<times/>
<apply>
<plus/>
<apply>
<times/>
<ci>beta_b</ci>
<cn xmlns:cellml="http://www.cellml.org/cellml/1.0#" cellml:units="dimensionless">4</cn>
</apply>
<ci>fprime</ci>
<apply>
<divide/>
<ci>omega</ci>
<apply>
<power/>
<ci>b</ci>
<cn xmlns:cellml="http://www.cellml.org/cellml/1.0#" cellml:units="dimensionless">4</cn>
</apply>
</apply>
</apply>
<ci>C_Ca4</ci>
</apply>
</apply>
</apply>
<apply>
<eq/>
<apply>
<diff/>
<bvar>
<ci>time</ci>
</bvar>
<ci>O_Ca</ci>
</apply>
<apply>
<minus/>
<apply>
<times/>
<ci>fprime</ci>
<ci>C_Ca4</ci>
</apply>
<apply>
<times/>
<ci>gprime</ci>
<ci>O_Ca</ci>
</apply>
</apply>
</apply>
</math>
</component>
<component name="L_type_Ca_current_y_gate">
<variable initial_value="0.798" name="y" public_interface="out" units="dimensionless"/>
<variable name="y_infinity" units="dimensionless"/>
<variable name="tau_y" units="second"/>
<variable name="V" public_interface="in" units="millivolt"/>
<variable name="time" public_interface="in" units="second"/>
<math xmlns="http://www.w3.org/1998/Math/MathML">
<apply>
<eq/>
<ci>y_infinity</ci>
<apply>
<plus/>
<apply>
<divide/>
<cn xmlns:cellml="http://www.cellml.org/cellml/1.0#" cellml:units="dimensionless">0.8</cn>
<apply>
<plus/>
<cn xmlns:cellml="http://www.cellml.org/cellml/1.0#" cellml:units="dimensionless">1</cn>
<apply>
<exp/>
<apply>
<divide/>
<apply>
<plus/>
<ci>V</ci>
<cn xmlns:cellml="http://www.cellml.org/cellml/1.0#" cellml:units="millivolt">12.5</cn>
</apply>
<cn xmlns:cellml="http://www.cellml.org/cellml/1.0#" cellml:units="millivolt">5</cn>
</apply>
</apply>
</apply>
</apply>
<cn xmlns:cellml="http://www.cellml.org/cellml/1.0#" cellml:units="dimensionless">0.2</cn>
</apply>
</apply>
<apply>
<eq/>
<ci>tau_y</ci>
<apply>
<divide/>
<apply>
<plus/>
<cn xmlns:cellml="http://www.cellml.org/cellml/1.0#" cellml:units="second">20</cn>
<apply>
<divide/>
<cn xmlns:cellml="http://www.cellml.org/cellml/1.0#" cellml:units="second">600</cn>
<apply>
<plus/>
<cn xmlns:cellml="http://www.cellml.org/cellml/1.0#" cellml:units="dimensionless">1</cn>
<apply>
<exp/>
<apply>
<divide/>
<apply>
<plus/>
<ci>V</ci>
<cn xmlns:cellml="http://www.cellml.org/cellml/1.0#" cellml:units="millivolt">20</cn>
</apply>
<cn xmlns:cellml="http://www.cellml.org/cellml/1.0#" cellml:units="millivolt">9.5</cn>
</apply>
</apply>
</apply>
</apply>
</apply>
<cn xmlns:cellml="http://www.cellml.org/cellml/1.0#" cellml:units="dimensionless">1000</cn>
</apply>
</apply>
<apply>
<eq/>
<apply>
<diff/>
<bvar>
<ci>time</ci>
</bvar>
<ci>y</ci>
</apply>
<apply>
<divide/>
<apply>
<minus/>
<ci>y_infinity</ci>
<ci>y</ci>
</apply>
<ci>tau_y</ci>
</apply>
</apply>
</math>
</component>
<component name="RyR_channel">
<variable cmeta:id="RyR_channel_J_rel" name="J_rel" public_interface="out" units="millimolar_per_second"/>
<variable initial_value="1800" name="v1" units="per_second"/>
<variable initial_value="1.215e13" name="k_a_plus" units="millimolar4_per_second"/>
<variable initial_value="576" name="k_a_minus" units="per_second"/>
<variable initial_value="4.05e9" name="k_b_plus" units="millimolar3_per_second"/>
<variable initial_value="1930" name="k_b_minus" units="per_second"/>
<variable initial_value="100" name="k_c_plus" units="per_second"/>
<variable initial_value="0.8" name="k_c_minus" units="per_second"/>
<variable initial_value="0" name="P_O1" units="dimensionless"/>
<variable initial_value="0" name="P_O2" units="dimensionless"/>
<variable initial_value="0.47" name="P_C1" units="dimensionless"/>
<variable initial_value="0.53" name="P_C2" units="dimensionless"/>
<variable initial_value="4" name="n" units="dimensionless"/>
<variable initial_value="3" name="m" units="dimensionless"/>
<variable name="time" public_interface="in" units="second"/>
<variable name="Ca_ss" public_interface="in" units="millimolar"/>
<variable name="Ca_JSR" public_interface="in" units="millimolar"/>
<math xmlns="http://www.w3.org/1998/Math/MathML">
<apply>
<eq/>
<apply>
<diff/>
<bvar>
<ci>time</ci>
</bvar>
<ci>P_C1</ci>
</apply>
<apply>
<plus/>
<apply>
<times/>
<apply>
<minus/>
<ci>k_a_plus</ci>
</apply>
<apply>
<power/>
<ci>Ca_ss</ci>
<ci>n</ci>
</apply>
<ci>P_C1</ci>
</apply>
<apply>
<times/>
<ci>k_a_minus</ci>
<ci>P_O1</ci>
</apply>
</apply>
</apply>
<apply>
<eq/>
<apply>
<diff/>
<bvar>
<ci>time</ci>
</bvar>
<ci>P_O1</ci>
</apply>
<apply>
<plus/>
<apply>
<minus/>
<apply>
<times/>
<ci>k_a_plus</ci>
<apply>
<power/>
<ci>Ca_ss</ci>
<ci>n</ci>
</apply>
<ci>P_C1</ci>
</apply>
<apply>
<plus/>
<apply>
<times/>
<ci>k_a_minus</ci>
<ci>P_O1</ci>
</apply>
<apply>
<times/>
<ci>k_b_plus</ci>
<apply>
<power/>
<ci>Ca_ss</ci>
<ci>m</ci>
</apply>
<ci>P_O1</ci>
</apply>
<apply>
<times/>
<ci>k_c_plus</ci>
<ci>P_O1</ci>
</apply>
</apply>
</apply>
<apply>
<times/>
<ci>k_b_minus</ci>
<ci>P_O2</ci>
</apply>
<apply>
<times/>
<ci>k_c_minus</ci>
<ci>P_C2</ci>
</apply>
</apply>
</apply>
<apply>
<eq/>
<apply>
<diff/>
<bvar>
<ci>time</ci>
</bvar>
<ci>P_O2</ci>
</apply>
<apply>
<minus/>
<apply>
<times/>
<ci>k_b_plus</ci>
<apply>
<power/>
<ci>Ca_ss</ci>
<ci>m</ci>
</apply>
<ci>P_O1</ci>
</apply>
<apply>
<times/>
<ci>k_b_minus</ci>
<ci>P_O2</ci>
</apply>
</apply>
</apply>
<apply>
<eq/>
<apply>
<diff/>
<bvar>
<ci>time</ci>
</bvar>
<ci>P_C2</ci>
</apply>
<apply>
<minus/>
<apply>
<times/>
<ci>k_c_plus</ci>
<ci>P_O1</ci>
</apply>
<apply>
<times/>
<ci>k_c_minus</ci>
<ci>P_C2</ci>
</apply>
</apply>
</apply>
<apply>
<eq/>
<ci>J_rel</ci>
<apply>
<times/>
<ci>v1</ci>
<apply>
<plus/>
<ci>P_O1</ci>
<ci>P_O2</ci>
</apply>
<apply>
<minus/>
<ci>Ca_JSR</ci>
<ci>Ca_ss</ci>
</apply>
</apply>
</apply>
</math>
</component>
<component name="SERCA2a_pump">
<variable cmeta:id="SERCA2a_pump_J_up" name="J_up" public_interface="out" units="millimolar_per_second"/>
<variable name="J_up_winslow" units="millimolar_per_second"/>
<variable initial_value="0.000168" name="K_fb" units="millimolar"/>
<variable initial_value="3.29" name="K_rb" units="millimolar"/>
<variable name="fb" units="dimensionless"/>
<variable name="rb" units="dimensionless"/>
<variable initial_value="0.0813" name="Vmaxf" units="millimolar_per_second"/>
<variable initial_value="0.318" name="Vmaxr" units="millimolar_per_second"/>
<variable initial_value="1" name="K_SR" units="dimensionless"/>
<variable initial_value="1.2" name="N_fb" units="dimensionless"/>
<variable initial_value="1" name="N_rb" units="dimensionless"/>
<variable name="time" public_interface="in" units="second"/>
<variable name="Ca_i" public_interface="in" units="millimolar"/>
<variable name="Ca_NSR" public_interface="in" units="millimolar"/>
<variable name="MgATP_i" public_interface="in" units="millimolar"/>
<variable name="MgATP_i0" public_interface="in" units="millimolar"/>
<math xmlns="http://www.w3.org/1998/Math/MathML">
<apply>
<eq/>
<ci>fb</ci>
<apply>
<power/>
<apply>
<divide/>
<ci>Ca_i</ci>
<ci>K_fb</ci>
</apply>
<ci>N_fb</ci>
</apply>
</apply>
<apply>
<eq/>
<ci>rb</ci>
<apply>
<power/>
<apply>
<divide/>
<ci>Ca_NSR</ci>
<ci>K_rb</ci>
</apply>
<ci>N_rb</ci>
</apply>
</apply>
<apply>
<eq/>
<ci>J_up</ci>
<apply>
<times/>
<apply>
<divide/>
<ci>MgATP_i</ci>
<ci>MgATP_i0</ci>
</apply>
<ci>J_up_winslow</ci>
</apply>
</apply>
<apply>
<eq/>
<ci>J_up_winslow</ci>
<apply>
<divide/>
<apply>
<times/>
<ci>K_SR</ci>
<apply>
<minus/>
<apply>
<times/>
<ci>Vmaxf</ci>
<ci>fb</ci>
</apply>
<apply>
<times/>
<ci>Vmaxr</ci>
<ci>rb</ci>
</apply>
</apply>
</apply>
<apply>
<plus/>
<cn xmlns:cellml="http://www.cellml.org/cellml/1.0#" cellml:units="dimensionless">1</cn>
<ci>fb</ci>
<ci>rb</ci>
</apply>
</apply>
</apply>
</math>
</component>
<component name="intracellular_Ca_fluxes">
<variable cmeta:id="intracellular_Ca_fluxes_J_tr" name="J_tr" public_interface="out" units="millimolar_per_second"/>
<variable cmeta:id="intracellular_Ca_fluxes_J_xfer" name="J_xfer" public_interface="out" units="millimolar_per_second"/>
<variable name="J_trpn" public_interface="out" units="millimolar_per_second"/>
<variable initial_value="0.0005747" name="tau_tr" units="second"/>
<variable initial_value="0.0267" name="tau_xfer" units="second"/>
<variable initial_value="0.98" name="HTRPNCa" units="millimolar"/>
<variable initial_value="0.078" name="LTRPNCa" units="millimolar"/>
<variable name="J_HTRPNCa" units="millimolar_per_second"/>
<variable name="J_LTRPNCa" units="millimolar_per_second"/>
<variable initial_value="0.14" name="HTRPN_tot" units="dimensionless"/>
<variable initial_value="0.07" name="LTRPN_tot" units="dimensionless"/>
<variable initial_value="20000" name="k_htrpn_plus" units="per_millimolar_second"/>
<variable initial_value="0.066" name="k_htrpn_minus" units="per_second"/>
<variable initial_value="40000" name="k_ltrpn_plus" units="per_millimolar_second"/>
<variable initial_value="40" name="k_ltrpn_minus" units="per_second"/>
<variable name="time" public_interface="in" units="second"/>
<variable name="Ca_ss" public_interface="in" units="millimolar"/>
<variable name="Ca_i" public_interface="in" units="millimolar"/>
<variable name="Ca_NSR" public_interface="in" units="millimolar"/>
<variable name="Ca_JSR" public_interface="in" units="millimolar"/>
<math xmlns="http://www.w3.org/1998/Math/MathML">
<apply>
<eq/>
<ci>J_tr</ci>
<apply>
<divide/>
<apply>
<minus/>
<ci>Ca_NSR</ci>
<ci>Ca_JSR</ci>
</apply>
<ci>tau_tr</ci>
</apply>
</apply>
<apply>
<eq/>
<ci>J_xfer</ci>
<apply>
<divide/>
<apply>
<minus/>
<ci>Ca_ss</ci>
<ci>Ca_i</ci>
</apply>
<ci>tau_xfer</ci>
</apply>
</apply>
<apply>
<eq/>
<ci>J_trpn</ci>
<apply>
<plus/>
<apply>
<times/>
<ci>HTRPN_tot</ci>
<ci>J_HTRPNCa</ci>
</apply>
<apply>
<times/>
<ci>LTRPN_tot</ci>
<ci>J_LTRPNCa</ci>
</apply>
</apply>
</apply>
<apply>
<eq/>
<ci>J_HTRPNCa</ci>
<apply>
<diff/>
<bvar>
<ci>time</ci>
</bvar>
<ci>HTRPNCa</ci>
</apply>
</apply>
<apply>
<eq/>
<apply>
<diff/>
<bvar>
<ci>time</ci>
</bvar>
<ci>HTRPNCa</ci>
</apply>
<apply>
<minus/>
<apply>
<times/>
<ci>k_htrpn_plus</ci>
<ci>Ca_i</ci>
<apply>
<minus/>
<cn xmlns:cellml="http://www.cellml.org/cellml/1.0#" cellml:units="millimolar">1</cn>
<ci>HTRPNCa</ci>
</apply>
</apply>
<apply>
<times/>
<ci>k_htrpn_minus</ci>
<ci>HTRPNCa</ci>
</apply>
</apply>
</apply>
<apply>
<eq/>
<ci>J_LTRPNCa</ci>
<apply>
<diff/>
<bvar>
<ci>time</ci>
</bvar>
<ci>LTRPNCa</ci>
</apply>
</apply>
<apply>
<eq/>
<apply>
<diff/>
<bvar>
<ci>time</ci>
</bvar>
<ci>LTRPNCa</ci>
</apply>
<apply>
<minus/>
<apply>
<times/>
<ci>k_ltrpn_plus</ci>
<ci>Ca_i</ci>
<apply>
<minus/>
<cn xmlns:cellml="http://www.cellml.org/cellml/1.0#" cellml:units="millimolar">1</cn>
<ci>LTRPNCa</ci>
</apply>
</apply>
<apply>
<times/>
<ci>k_ltrpn_minus</ci>
<ci>LTRPNCa</ci>
</apply>
</apply>
</apply>
</math>
</component>
<component name="intracellular_ion_concentrations">
<variable initial_value="10" name="Na_i" public_interface="out" units="millimolar"/>
<variable initial_value="8.464E-5" name="Ca_i" public_interface="out" units="millimolar"/>
<variable initial_value="159.48" name="K_i" public_interface="out" units="millimolar"/>
<variable initial_value="1.315E-4" name="Ca_ss" public_interface="out" units="millimolar"/>
<variable initial_value="0.2616" name="Ca_JSR" public_interface="out" units="millimolar"/>
<variable initial_value="0.2620" name="Ca_NSR" public_interface="out" units="millimolar"/>
<variable initial_value="0.0001534" name="A_cap" units="cm2"/>
<variable initial_value="0.00002584" name="V_myo" units="microlitre"/>
<variable initial_value="0.00000016" name="V_JSR" units="microlitre"/>
<variable initial_value="0.0000021" name="V_NSR" units="microlitre"/>
<variable initial_value="0.0000000012" name="V_ss" units="microlitre"/>
<variable initial_value="0.00238" name="K_mCMDN" units="millimolar"/>
<variable initial_value="0.00015" name="K_mEGTA" units="millimolar"/>
<variable initial_value="0.8" name="K_mCSQN" units="millimolar"/>
<variable initial_value="0.05" name="CMDN_tot" units="millimolar"/>
<variable initial_value="0" name="EGTA_tot" units="millimolar"/>
<variable initial_value="15" name="CSQN_tot" units="millimolar"/>
<variable name="beta_i" units="dimensionless"/>
<variable name="beta_SS" units="dimensionless"/>
<variable name="beta_JSR" units="dimensionless"/>
<variable name="time" public_interface="in" units="second"/>
<variable name="F" public_interface="in" units="coulomb_per_millimole"/>
<variable name="C_sc" public_interface="in" units="microF_per_cm2"/>
<variable name="i_Na" public_interface="in" units="microA_per_microF"/>
<variable name="i_Ca" public_interface="in" units="microA_per_microF"/>
<variable name="i_Na_b" public_interface="in" units="microA_per_microF"/>
<variable name="i_NaCa" public_interface="in" units="microA_per_microF"/>
<variable name="i_NaK" public_interface="in" units="microA_per_microF"/>
<variable name="i_Ca_K" public_interface="in" units="microA_per_microF"/>
<variable name="i_Kr" public_interface="in" units="microA_per_microF"/>
<variable name="i_Ks" public_interface="in" units="microA_per_microF"/>
<variable name="i_K1" public_interface="in" units="microA_per_microF"/>
<variable name="i_Kp" public_interface="in" units="microA_per_microF"/>
<variable name="i_to1" public_interface="in" units="microA_per_microF"/>
<variable name="i_p_Ca" public_interface="in" units="microA_per_microF"/>
<variable name="i_Ca_b" public_interface="in" units="microA_per_microF"/>
<variable name="J_up" public_interface="in" units="millimolar_per_second"/>
<variable name="J_rel" public_interface="in" units="millimolar_per_second"/>
<variable name="J_xfer" public_interface="in" units="millimolar_per_second"/>
<variable name="J_trpn" public_interface="in" units="millimolar_per_second"/>
<variable name="J_tr" public_interface="in" units="millimolar_per_second"/>
<variable name="k_plus_CaATP" public_interface="in" units="per_millimolar_second"/>
<variable name="k_minus_CaATP" public_interface="in" units="per_second"/>
<variable name="k_plus_CaADP" public_interface="in" units="per_millimolar_second"/>
<variable name="k_minus_CaADP" public_interface="in" units="per_second"/>
<variable name="CaADP_i" public_interface="in" units="millimolar"/>
<variable name="CaADP_ss" public_interface="in" units="millimolar"/>
<variable name="CaATP_ss" public_interface="in" units="millimolar"/>
<variable name="ATP_i" public_interface="in" units="millimolar"/>
<variable name="ADP_i" public_interface="in" units="millimolar"/>
<variable name="ADP_ss" public_interface="in" units="millimolar"/>
<variable name="ATP_ss" public_interface="in" units="millimolar"/>
<variable name="CaATP_i" public_interface="in" units="millimolar"/>
<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>beta_i</ci>
<apply>
<plus/>
<apply>
<minus/>
<ci>J_xfer</ci>
<apply>
<plus/>
<ci>J_up</ci>
<ci>J_trpn</ci>
</apply>
</apply>
<apply>
<minus/>
<apply>
<times/>
<apply>
<minus/>
<apply>
<plus/>
<ci>i_p_Ca</ci>
<ci>i_Ca_b</ci>
</apply>
<apply>
<times/>
<cn xmlns:cellml="http://www.cellml.org/cellml/1.0#" cellml:units="dimensionless">2</cn>
<ci>i_NaCa</ci>
</apply>
</apply>
<apply>
<divide/>
<apply>
<times/>
<ci>A_cap</ci>
<ci>C_sc</ci>
</apply>
<apply>
<times/>
<cn xmlns:cellml="http://www.cellml.org/cellml/1.0#" cellml:units="dimensionless">2</cn>
<ci>V_myo</ci>
<ci>F</ci>
</apply>
</apply>
</apply>
</apply>
<apply>
<minus/>
<apply>
<plus/>
<apply>
<times/>
<ci> k_minus_CaATP </ci>
<ci> CaATP_i </ci>
</apply>
<apply>
<times/>
<ci> k_minus_CaADP </ci>
<ci> CaADP_i </ci>
</apply>
</apply>
<apply>
<plus/>
<apply>
<times/>
<ci> k_plus_CaATP </ci>
<ci> Ca_i </ci>
<ci> ATP_i </ci>
</apply>
<apply>
<times/>
<ci> k_plus_CaADP </ci>
<ci> Ca_i </ci>
<ci> ADP_i </ci>
</apply>
</apply>
</apply>
</apply>
</apply>
</apply>
<apply>
<eq/>
<apply>
<diff/>
<bvar>
<ci>time</ci>
</bvar>
<ci>Na_i</ci>
</apply>
<apply>
<divide/>
<apply>
<times/>
<apply>
<minus/>
<cn xmlns:cellml="http://www.cellml.org/cellml/1.0#" cellml:units="dimensionless">0</cn>
</apply>
<apply>
<plus/>
<ci>i_Na</ci>
<ci>i_Na_b</ci>
<apply>
<times/>
<ci>i_NaCa</ci>
<cn xmlns:cellml="http://www.cellml.org/cellml/1.0#" cellml:units="dimensionless">3</cn>
</apply>
<apply>
<times/>
<ci>i_NaK</ci>
<cn xmlns:cellml="http://www.cellml.org/cellml/1.0#" cellml:units="dimensionless">3</cn>
</apply>
</apply>
<ci>A_cap</ci>
<cn xmlns:cellml="http://www.cellml.org/cellml/1.0#" cellml:units="microF_per_cm2">1</cn>
</apply>
<apply>
<times/>
<ci>V_myo</ci>
<ci>F</ci>
</apply>
</apply>
</apply>
<apply>
<eq/>
<apply>
<diff/>
<bvar>
<ci>time</ci>
</bvar>
<ci>K_i</ci>
</apply>
<apply>
<divide/>
<apply>
<times/>
<apply>
<minus/>
<cn xmlns:cellml="http://www.cellml.org/cellml/1.0#" cellml:units="dimensionless">0</cn>
</apply>
<apply>
<plus/>
<ci>i_Ca_K</ci>
<ci>i_Kr</ci>
<ci>i_Ks</ci>
<ci>i_K1</ci>
<ci>i_Kp</ci>
<ci>i_to1</ci>
<apply>
<times/>
<ci>i_NaK</ci>
<apply>
<minus/>
<cn xmlns:cellml="http://www.cellml.org/cellml/1.0#" cellml:units="dimensionless">2</cn>
</apply>
</apply>
</apply>
<ci>A_cap</ci>
<cn xmlns:cellml="http://www.cellml.org/cellml/1.0#" cellml:units="microF_per_cm2">1</cn>
</apply>
<apply>
<times/>
<ci>V_myo</ci>
<ci>F</ci>
</apply>
</apply>
</apply>
<apply>
<eq/>
<ci>beta_i</ci>
<apply>
<divide/>
<cn xmlns:cellml="http://www.cellml.org/cellml/1.0#" cellml:units="dimensionless">1</cn>
<apply>
<plus/>
<cn xmlns:cellml="http://www.cellml.org/cellml/1.0#" cellml:units="dimensionless">1</cn>
<apply>
<divide/>
<apply>
<times/>
<ci>CMDN_tot</ci>
<ci>K_mCMDN</ci>
</apply>
<apply>
<power/>
<apply>
<plus/>
<ci>K_mCMDN</ci>
<ci>Ca_i</ci>
</apply>
<cn xmlns:cellml="http://www.cellml.org/cellml/1.0#" cellml:units="dimensionless">2</cn>
</apply>
</apply>
<apply>
<divide/>
<apply>
<times/>
<ci>EGTA_tot</ci>
<ci>K_mEGTA</ci>
</apply>
<apply>
<power/>
<apply>
<plus/>
<ci>K_mEGTA</ci>
<ci>Ca_i</ci>
</apply>
<cn xmlns:cellml="http://www.cellml.org/cellml/1.0#" cellml:units="dimensionless">2</cn>
</apply>
</apply>
</apply>
</apply>
</apply>
<apply>
<eq/>
<ci>beta_SS</ci>
<apply>
<divide/>
<cn xmlns:cellml="http://www.cellml.org/cellml/1.0#" cellml:units="dimensionless">1</cn>
<apply>
<plus/>
<cn xmlns:cellml="http://www.cellml.org/cellml/1.0#" cellml:units="dimensionless">1</cn>
<apply>
<divide/>
<apply>
<times/>
<ci>CMDN_tot</ci>
<ci>K_mCMDN</ci>
</apply>
<apply>
<power/>
<apply>
<plus/>
<ci>K_mCMDN</ci>
<ci>Ca_ss</ci>
</apply>
<cn xmlns:cellml="http://www.cellml.org/cellml/1.0#" cellml:units="dimensionless">2</cn>
</apply>
</apply>
<apply>
<divide/>
<apply>
<times/>
<ci>EGTA_tot</ci>
<ci>K_mEGTA</ci>
</apply>
<apply>
<power/>
<apply>
<plus/>
<ci>K_mEGTA</ci>
<ci>Ca_ss</ci>
</apply>
<cn xmlns:cellml="http://www.cellml.org/cellml/1.0#" cellml:units="dimensionless">2</cn>
</apply>
</apply>
</apply>
</apply>
</apply>
<apply>
<eq/>
<ci>beta_JSR</ci>
<apply>
<divide/>
<cn xmlns:cellml="http://www.cellml.org/cellml/1.0#" cellml:units="dimensionless">1</cn>
<apply>
<plus/>
<cn xmlns:cellml="http://www.cellml.org/cellml/1.0#" cellml:units="dimensionless">1</cn>
<apply>
<divide/>
<apply>
<times/>
<ci>CSQN_tot</ci>
<ci>K_mCSQN</ci>
</apply>
<apply>
<power/>
<apply>
<plus/>
<ci>K_mCSQN</ci>
<ci>Ca_JSR</ci>
</apply>
<cn xmlns:cellml="http://www.cellml.org/cellml/1.0#" cellml:units="dimensionless">2</cn>
</apply>
</apply>
</apply>
</apply>
</apply>
<apply>
<eq/>
<apply>
<diff/>
<bvar>
<ci>time</ci>
</bvar>
<ci>Ca_ss</ci>
</apply>
<apply>
<times/>
<ci>beta_SS</ci>
<apply>
<minus/>
<apply>
<plus/>
<apply>
<divide/>
<apply>
<times/>
<ci>J_rel</ci>
<ci>V_JSR</ci>
</apply>
<ci>V_ss</ci>
</apply>
<apply>
<times/>
<ci>k_minus_CaATP</ci>
<ci>CaATP_ss</ci>
</apply>
<apply>
<times/>
<ci>k_minus_CaADP</ci>
<ci>CaADP_ss</ci>
</apply>
</apply>
<apply>
<plus/>
<apply>
<divide/>
<apply>
<times/>
<ci>J_xfer</ci>
<ci>V_myo</ci>
</apply>
<ci>V_ss</ci>
</apply>
<apply>
<times/>
<ci>i_Ca</ci>
<apply>
<divide/>
<apply>
<times/>
<ci>A_cap</ci>
<cn xmlns:cellml="http://www.cellml.org/cellml/1.0#" cellml:units="microF_per_cm2">1</cn>
</apply>
<apply>
<times/>
<cn xmlns:cellml="http://www.cellml.org/cellml/1.0#" cellml:units="dimensionless">2</cn>
<ci>V_ss</ci>
<ci>F</ci>
</apply>
</apply>
</apply>
<apply>
<times/>
<ci>k_plus_CaATP</ci>
<ci>Ca_ss</ci>
<ci>ATP_ss</ci>
</apply>
<apply>
<times/>
<ci>k_plus_CaADP</ci>
<ci>Ca_ss</ci>
<ci>ADP_ss</ci>
</apply>
</apply>
</apply>
</apply>
</apply>
<apply>
<eq/>
<apply>
<diff/>
<bvar>
<ci>time</ci>
</bvar>
<ci>Ca_JSR</ci>
</apply>
<apply>
<times/>
<ci>beta_JSR</ci>
<apply>
<minus/>
<ci>J_tr</ci>
<ci>J_rel</ci>
</apply>
</apply>
</apply>
<apply>
<eq/>
<apply>
<diff/>
<bvar>
<ci>time</ci>
</bvar>
<ci>Ca_NSR</ci>
</apply>
<apply>
<minus/>
<apply>
<divide/>
<apply>
<times/>
<ci>J_up</ci>
<ci>V_myo</ci>
</apply>
<ci>V_NSR</ci>
</apply>
<apply>
<divide/>
<apply>
<times/>
<ci>J_tr</ci>
<ci>V_JSR</ci>
</apply>
<ci>V_NSR</ci>
</apply>
</apply>
</apply>
</math>
</component>
<component name="Ca_and_Mg_buffering_by_ATP">
<variable initial_value="0.25E-3" name="CaATP_ss" public_interface="out" units="millimolar"/>
<variable name="ATP_ss" public_interface="out" units="millimolar"/>
<variable cmeta:id="Ca_and_Mg_buffering_by_ATP_MgATP_i" initial_value="6.4395" name="MgATP_i" public_interface="out" units="millimolar"/>
<variable initial_value="2.888" name="MgATP_i0" public_interface="out" units="millimolar"/>
<variable initial_value="225000.0" name="k_plus_CaATP" public_interface="out" units="per_millimolar_second"/>
<variable initial_value="45000.0" name="k_minus_CaATP" public_interface="out" units="per_second"/>
<variable initial_value="125000.0" name="k_plus_CaADP" public_interface="out" units="per_millimolar_second"/>
<variable initial_value="193500" name="k_minus_CaADP" public_interface="out" units="per_second"/>
<variable cmeta:id="Ca_and_Mg_buffering_by_ATP_CaADP_i" initial_value="0.11E-6" name="CaADP_i" public_interface="out" units="millimolar"/>
<variable initial_value="0.13E-6" name="CaADP_ss" public_interface="out" units="millimolar"/>
<variable name="ATP_i" public_interface="out" units="millimolar"/>
<variable name="ADP_i" public_interface="out" units="millimolar"/>
<variable name="ADP_ss" public_interface="out" units="millimolar"/>
<variable initial_value="0.237E-3" name="CaATP_i" public_interface="out" units="millimolar"/>
<variable initial_value="1.0" name="Mg_ss" units="millimolar"/>
<variable initial_value="1.0" name="Mg_i" units="millimolar"/>
<variable initial_value="0.298E-2" name="MgADP_i" units="millimolar"/>
<variable initial_value="0.298E-2" name="MgADP_ss" units="millimolar"/>
<variable initial_value="6.4395" name="MgATP_ss" units="millimolar"/>
<variable initial_value="7.0" name="ATP_tot" units="millimolar"/>
<variable initial_value="125000.0" name="k_plus_MgATP" units="per_millimolar_second"/>
<variable initial_value="10875.0" name="k_minus_MgATP" units="per_second"/>
<variable name="Jxfer_CaATP" units="millimolar_per_second"/>
<variable name="Jxfer_MgATP" units="millimolar_per_second"/>
<variable cmeta:id="Ca_and_Mg_buffering_by_ATP_Jxfer_Mg" name="Jxfer_Mg" units="millimolar_per_second"/>
<variable initial_value="0.0534" name="tau_xfer_CaATP" units="second"/>
<variable initial_value="0.0534" name="tau_xfer_MgATP" units="second"/>
<variable initial_value="0.0267" name="tau_xfer_Mg" units="second"/>
<variable initial_value="0.005" name="ADP_tot" units="millimolar"/>
<variable initial_value="125000.0" name="k_plus_MgADP" units="per_millimolar_second"/>
<variable initial_value="84500.0" name="k_minus_MgADP" units="per_second"/>
<variable cmeta:id="Ca_and_Mg_buffering_by_ATP_Jxfer_CaADP" name="Jxfer_CaADP" units="millimolar_per_second"/>
<variable name="Jxfer_MgADP" units="millimolar_per_second"/>
<variable initial_value="0.0534" name="tau_xfer_CaADP" units="second"/>
<variable initial_value="0.0534" name="tau_xfer_MgADP" units="second"/>
<variable name="time" public_interface="in" units="second"/>
<variable name="Ca_ss" public_interface="in" units="millimolar"/>
<variable name="Ca_i" public_interface="in" units="millimolar"/>
<variable name="V_myo" public_interface="in" units="microlitre"/>
<variable name="V_ss" public_interface="in" units="microlitre"/>
<math xmlns="http://www.w3.org/1998/Math/MathML">
<apply id="ATP_ss_calculation">
<eq/>
<ci> ATP_ss </ci>
<apply>
<minus/>
<ci> ATP_tot </ci>
<apply>
<plus/>
<ci> CaATP_ss </ci>
<ci> MgATP_ss </ci>
</apply>
</apply>
</apply>
<apply id="CaATP_ss_diff_eq">
<eq/>
<apply>
<diff/>
<bvar>
<ci> time </ci>
</bvar>
<ci> CaATP_ss </ci>
</apply>
<apply>
<minus/>
<apply>
<times/>
<ci> k_plus_CaATP </ci>
<ci> Ca_ss </ci>
<ci> ATP_ss </ci>
</apply>
<apply>
<plus/>
<apply>
<times/>
<ci> Jxfer_CaATP </ci>
<apply>
<divide/>
<ci> V_myo </ci>
<ci> V_ss </ci>
</apply>
</apply>
<apply>
<times/>
<ci> k_minus_CaATP </ci>
<ci> CaATP_ss </ci>
</apply>
</apply>
</apply>
</apply>
<apply id="MgATP_ss_diff_eq">
<eq/>
<apply>
<diff/>
<bvar>
<ci> time </ci>
</bvar>
<ci> MgATP_ss </ci>
</apply>
<apply>
<minus/>
<apply>
<times/>
<ci> k_plus_MgATP </ci>
<ci> Mg_ss </ci>
<ci> ATP_ss </ci>
</apply>
<apply>
<plus/>
<apply>
<times/>
<ci> Jxfer_MgATP </ci>
<apply>
<divide/>
<ci> V_myo </ci>
<ci> V_ss </ci>
</apply>
</apply>
<apply>
<times/>
<ci> k_minus_MgATP </ci>
<ci> MgATP_ss </ci>
</apply>
</apply>
</apply>
</apply>
<apply id="ATP_i_calculation">
<eq/>
<ci> ATP_i </ci>
<apply>
<minus/>
<ci> ATP_tot </ci>
<apply>
<plus/>
<ci> CaATP_i </ci>
<ci> MgATP_i </ci>
</apply>
</apply>
</apply>
<apply id="CaATP_i_diff_eq">
<eq/>
<apply>
<diff/>
<bvar>
<ci> time </ci>
</bvar>
<ci> CaATP_i </ci>
</apply>
<apply>
<minus/>
<apply>
<plus/>
<ci> Jxfer_CaATP </ci>
<apply>
<times/>
<ci> k_plus_CaATP </ci>
<ci> Ca_i </ci>
<ci> ATP_i </ci>
</apply>
</apply>
<apply>
<times/>
<ci> k_minus_CaATP </ci>
<ci> CaATP_i </ci>
</apply>
</apply>
</apply>
<apply id="MgATP_i_diff_eq">
<eq/>
<apply>
<diff/>
<bvar>
<ci> time </ci>
</bvar>
<ci> MgATP_i </ci>
</apply>
<apply>
<minus/>
<apply>
<plus/>
<ci> Jxfer_MgATP </ci>
<apply>
<times/>
<ci> k_plus_MgATP </ci>
<ci> Mg_i </ci>
<ci> ATP_i </ci>
</apply>
</apply>
<apply>
<times/>
<ci> k_minus_MgATP </ci>
<ci> MgATP_i </ci>
</apply>
</apply>
</apply>
<apply id="Jxfer_CaATP_calculation">
<eq/>
<ci> Jxfer_CaATP </ci>
<apply>
<divide/>
<apply>
<minus/>
<ci> CaATP_ss </ci>
<ci> CaATP_i </ci>
</apply>
<ci> tau_xfer_CaATP </ci>
</apply>
</apply>
<apply id="Jxfer_MgATP_calculation">
<eq/>
<ci> Jxfer_MgATP </ci>
<apply>
<divide/>
<apply>
<minus/>
<ci> MgATP_ss </ci>
<ci> MgATP_i </ci>
</apply>
<ci> tau_xfer_MgATP </ci>
</apply>
</apply>
<apply id="ADP_ss_calculation">
<eq/>
<ci> ADP_ss </ci>
<apply>
<minus/>
<ci> ADP_tot </ci>
<apply>
<plus/>
<ci> CaADP_ss </ci>
<ci> MgADP_ss </ci>
</apply>
</apply>
</apply>
<apply id="CaADP_ss_diff_eq">
<eq/>
<apply>
<diff/>
<bvar>
<ci> time </ci>
</bvar>
<ci> CaADP_ss </ci>
</apply>
<apply>
<minus/>
<apply>
<times/>
<ci> k_plus_CaADP </ci>
<ci> Ca_ss </ci>
<ci> ADP_ss </ci>
</apply>
<apply>
<plus/>
<apply>
<times/>
<ci> Jxfer_CaADP </ci>
<apply>
<divide/>
<ci> V_myo </ci>
<ci> V_ss </ci>
</apply>
</apply>
<apply>
<times/>
<ci> k_minus_CaADP </ci>
<ci> CaADP_ss </ci>
</apply>
</apply>
</apply>
</apply>
<apply id="MgADP_ss_diff_eq">
<eq/>
<apply>
<diff/>
<bvar>
<ci> time </ci>
</bvar>
<ci> MgADP_ss </ci>
</apply>
<apply>
<minus/>
<apply>
<times/>
<ci> k_plus_MgADP </ci>
<ci> Mg_ss </ci>
<ci> ADP_ss </ci>
</apply>
<apply>
<plus/>
<apply>
<times/>
<ci> Jxfer_MgADP </ci>
<apply>
<divide/>
<ci> V_myo </ci>
<ci> V_ss </ci>
</apply>
</apply>
<apply>
<times/>
<ci> k_minus_MgADP </ci>
<ci> MgADP_ss </ci>
</apply>
</apply>
</apply>
</apply>
<apply id="ADP_i_calculation">
<eq/>
<ci> ADP_i </ci>
<apply>
<minus/>
<ci> ADP_tot </ci>
<apply>
<plus/>
<ci> CaADP_i </ci>
<ci> MgADP_i </ci>
</apply>
</apply>
</apply>
<apply id="CaADP_i_diff_eq">
<eq/>
<apply>
<diff/>
<bvar>
<ci> time </ci>
</bvar>
<ci> CaADP_i </ci>
</apply>
<apply>
<minus/>
<apply>
<plus/>
<ci> Jxfer_CaADP </ci>
<apply>
<times/>
<ci> k_plus_CaADP </ci>
<ci> Ca_i </ci>
<ci> ADP_i </ci>
</apply>
</apply>
<apply>
<times/>
<ci> k_minus_CaADP </ci>
<ci> CaADP_i </ci>
</apply>
</apply>
</apply>
<apply id="MgADP_i_diff_eq">
<eq/>
<apply>
<diff/>
<bvar>
<ci> time </ci>
</bvar>
<ci> MgADP_i </ci>
</apply>
<apply>
<minus/>
<apply>
<plus/>
<ci> Jxfer_MgADP </ci>
<apply>
<times/>
<ci> k_plus_MgADP </ci>
<ci> Mg_i </ci>
<ci> ADP_i </ci>
</apply>
</apply>
<apply>
<times/>
<ci> k_minus_MgADP </ci>
<ci> MgADP_i </ci>
</apply>
</apply>
</apply>
<apply id="Jxfer_CaADP_calculation">
<eq/>
<ci> Jxfer_CaADP </ci>
<apply>
<divide/>
<apply>
<minus/>
<ci> CaADP_ss </ci>
<ci> CaADP_i </ci>
</apply>
<ci> tau_xfer_CaADP </ci>
</apply>
</apply>
<apply id="Jxfer_MgADP_calculation">
<eq/>
<ci> Jxfer_MgADP </ci>
<apply>
<divide/>
<apply>
<minus/>
<ci> MgADP_ss </ci>
<ci> MgADP_i </ci>
</apply>
<ci> tau_xfer_MgADP </ci>
</apply>
</apply>
<apply id="Mg_ss_calculation">
<eq/>
<apply>
<diff/>
<bvar>
<ci> time </ci>
</bvar>
<ci> Mg_ss </ci>
</apply>
<apply>
<minus/>
<apply>
<plus/>
<apply>
<times/>
<ci> k_minus_MgATP </ci>
<ci> MgATP_ss </ci>
</apply>
<apply>
<times/>
<ci> k_minus_MgADP </ci>
<ci> MgADP_ss </ci>
</apply>
</apply>
<apply>
<plus/>
<apply>
<times/>
<ci> k_plus_MgATP </ci>
<ci> Mg_ss </ci>
<ci> ATP_ss </ci>
</apply>
<apply>
<times/>
<ci> k_plus_MgADP </ci>
<ci> Mg_ss </ci>
<ci> ADP_ss </ci>
</apply>
<apply>
<times/>
<ci> Jxfer_Mg </ci>
<apply>
<divide/>
<ci> V_myo </ci>
<ci> V_ss </ci>
</apply>
</apply>
</apply>
</apply>
</apply>
<apply id="Mg_i_calculation">
<eq/>
<apply>
<diff/>
<bvar>
<ci> time </ci>
</bvar>
<ci> Mg_i </ci>
</apply>
<apply>
<minus/>
<apply>
<plus/>
<ci> Jxfer_Mg </ci>
<apply>
<times/>
<ci> k_minus_MgATP </ci>
<ci> MgATP_i </ci>
</apply>
<apply>
<times/>
<ci> k_minus_MgADP </ci>
<ci> MgADP_i </ci>
</apply>
</apply>
<apply>
<plus/>
<apply>
<times/>
<ci> k_plus_MgATP </ci>
<ci> Mg_i </ci>
<ci> ATP_i </ci>
</apply>
<apply>
<times/>
<ci> k_plus_MgADP </ci>
<ci> Mg_i </ci>
<ci> ADP_i </ci>
</apply>
</apply>
</apply>
</apply>
<apply id="Jxfer_Mg_calculation">
<eq/>
<ci> Jxfer_Mg </ci>
<apply>
<divide/>
<apply>
<minus/>
<ci> Mg_ss </ci>
<ci> Mg_i </ci>
</apply>
<ci> tau_xfer_Mg </ci>
</apply>
</apply>
</math>
</component>
<component name="extracellular_ion_concentrations">
<variable initial_value="138" name="Na_o" public_interface="out" units="millimolar"/>
<variable initial_value="2" name="Ca_o" public_interface="out" units="millimolar"/>
<variable initial_value="4" name="K_o" public_interface="out" units="millimolar"/>
</component>
<component name="model_parameters">
<variable initial_value="0.00002584" name="V_myo" public_interface="out" units="microlitre"/>
<variable initial_value="0.0000000012" name="V_ss" public_interface="out" units="microlitre"/>
</component>
<group>
<relationship_ref relationship="encapsulation"/>
<component_ref component="fast_sodium_current">
<component_ref component="fast_sodium_current_m_gate"/>
<component_ref component="fast_sodium_current_h_gate"/>
<component_ref component="fast_sodium_current_j_gate"/>
</component_ref>
<component_ref component="rapid_activating_delayed_rectifiyer_K_current">
<component_ref component="rapid_activating_delayed_rectifiyer_K_current_X_kr_gate"/>
</component_ref>
<component_ref component="slow_activating_delayed_rectifiyer_K_current">
<component_ref component="slow_activating_delayed_rectifiyer_K_current_X_ks_gate"/>
</component_ref>
<component_ref component="transient_outward_potassium_current">
<component_ref component="transient_outward_potassium_current_X_to1_gate"/>
<component_ref component="transient_outward_potassium_current_Y_to1_gate"/>
</component_ref>
<component_ref component="time_independent_potassium_current">
<component_ref component="time_independent_potassium_current_K1_gate"/>
</component_ref>
<component_ref component="plateau_potassium_current">
<component_ref component="plateau_potassium_current_Kp_gate"/>
</component_ref>
<component_ref component="L_type_Ca_current">
<component_ref component="L_type_Ca_current_y_gate"/>
</component_ref>
</group>
<connection>
<map_components component_1="membrane" component_2="environment"/>
<map_variables variable_1="time" variable_2="time"/>
</connection>
<connection>
<map_components component_1="fast_sodium_current" component_2="environment"/>
<map_variables variable_1="time" variable_2="time"/>
</connection>
<connection>
<map_components component_1="rapid_activating_delayed_rectifiyer_K_current" component_2="environment"/>
<map_variables variable_1="time" variable_2="time"/>
</connection>
<connection>
<map_components component_1="slow_activating_delayed_rectifiyer_K_current" component_2="environment"/>
<map_variables variable_1="time" variable_2="time"/>
</connection>
<connection>
<map_components component_1="transient_outward_potassium_current" component_2="environment"/>
<map_variables variable_1="time" variable_2="time"/>
</connection>
<connection>
<map_components component_1="time_independent_potassium_current" component_2="environment"/>
<map_variables variable_1="time" variable_2="time"/>
</connection>
<connection>
<map_components component_1="plateau_potassium_current" component_2="environment"/>
<map_variables variable_1="time" variable_2="time"/>
</connection>
<connection>
<map_components component_1="Na_Ca_exchanger" component_2="environment"/>
<map_variables variable_1="time" variable_2="time"/>
</connection>
<connection>
<map_components component_1="sodium_potassium_pump" component_2="environment"/>
<map_variables variable_1="time" variable_2="time"/>
</connection>
<connection>
<map_components component_1="sarcolemmal_calcium_pump" component_2="environment"/>
<map_variables variable_1="time" variable_2="time"/>
</connection>
<connection>
<map_components component_1="calcium_background_current" component_2="environment"/>
<map_variables variable_1="time" variable_2="time"/>
</connection>
<connection>
<map_components component_1="sodium_background_current" component_2="environment"/>
<map_variables variable_1="time" variable_2="time"/>
</connection>
<connection>
<map_components component_1="L_type_Ca_current" component_2="environment"/>
<map_variables variable_1="time" variable_2="time"/>
</connection>
<connection>
<map_components component_1="RyR_channel" component_2="environment"/>
<map_variables variable_1="time" variable_2="time"/>
</connection>
<connection>
<map_components component_1="SERCA2a_pump" component_2="environment"/>
<map_variables variable_1="time" variable_2="time"/>
</connection>
<connection>
<map_components component_1="intracellular_Ca_fluxes" component_2="environment"/>
<map_variables variable_1="time" variable_2="time"/>
</connection>
<connection>
<map_components component_1="intracellular_ion_concentrations" component_2="environment"/>
<map_variables variable_1="time" variable_2="time"/>
</connection>
<connection>
<map_components component_1="Ca_and_Mg_buffering_by_ATP" component_2="environment"/>
<map_variables variable_1="time" variable_2="time"/>
</connection>
<connection>
<map_components component_1="membrane" component_2="fast_sodium_current"/>
<map_variables variable_1="V" variable_2="V"/>
<map_variables variable_1="R" variable_2="R"/>
<map_variables variable_1="T" variable_2="T"/>
<map_variables variable_1="F" variable_2="F"/>
<map_variables variable_1="i_Na" variable_2="i_Na"/>
</connection>
<connection>
<map_components component_1="membrane" component_2="rapid_activating_delayed_rectifiyer_K_current"/>
<map_variables variable_1="V" variable_2="V"/>
<map_variables variable_1="i_Kr" variable_2="i_Kr"/>
<map_variables variable_1="R" variable_2="R"/>
<map_variables variable_1="T" variable_2="T"/>
<map_variables variable_1="F" variable_2="F"/>
</connection>
<connection>
<map_components component_1="membrane" component_2="slow_activating_delayed_rectifiyer_K_current"/>
<map_variables variable_1="V" variable_2="V"/>
<map_variables variable_1="i_Ks" variable_2="i_Ks"/>
<map_variables variable_1="R" variable_2="R"/>
<map_variables variable_1="T" variable_2="T"/>
<map_variables variable_1="F" variable_2="F"/>
</connection>
<connection>
<map_components component_1="membrane" component_2="transient_outward_potassium_current"/>
<map_variables variable_1="V" variable_2="V"/>
<map_variables variable_1="i_to1" variable_2="i_to1"/>
</connection>
<connection>
<map_components component_1="membrane" component_2="time_independent_potassium_current"/>
<map_variables variable_1="V" variable_2="V"/>
<map_variables variable_1="i_K1" variable_2="i_K1"/>
<map_variables variable_1="R" variable_2="R"/>
<map_variables variable_1="T" variable_2="T"/>
<map_variables variable_1="F" variable_2="F"/>
</connection>
<connection>
<map_components component_1="membrane" component_2="plateau_potassium_current"/>
<map_variables variable_1="V" variable_2="V"/>
<map_variables variable_1="i_Kp" variable_2="i_Kp"/>
</connection>
<connection>
<map_components component_1="membrane" component_2="Na_Ca_exchanger"/>
<map_variables variable_1="V" variable_2="V"/>
<map_variables variable_1="i_NaCa" variable_2="i_NaCa"/>
<map_variables variable_1="R" variable_2="R"/>
<map_variables variable_1="T" variable_2="T"/>
<map_variables variable_1="F" variable_2="F"/>
</connection>
<connection>
<map_components component_1="membrane" component_2="sodium_potassium_pump"/>
<map_variables variable_1="V" variable_2="V"/>
<map_variables variable_1="i_NaK" variable_2="i_NaK"/>
<map_variables variable_1="R" variable_2="R"/>
<map_variables variable_1="T" variable_2="T"/>
<map_variables variable_1="F" variable_2="F"/>
</connection>
<connection>
<map_components component_1="membrane" component_2="sarcolemmal_calcium_pump"/>
<map_variables variable_1="i_p_Ca" variable_2="i_p_Ca"/>
</connection>
<connection>
<map_components component_1="membrane" component_2="calcium_background_current"/>
<map_variables variable_1="V" variable_2="V"/>
<map_variables variable_1="i_Ca_b" variable_2="i_Ca_b"/>
<map_variables variable_1="R" variable_2="R"/>
<map_variables variable_1="T" variable_2="T"/>
<map_variables variable_1="F" variable_2="F"/>
</connection>
<connection>
<map_components component_1="membrane" component_2="sodium_background_current"/>
<map_variables variable_1="V" variable_2="V"/>
<map_variables variable_1="i_Na_b" variable_2="i_Na_b"/>
</connection>
<connection>
<map_components component_1="membrane" component_2="L_type_Ca_current"/>
<map_variables variable_1="V" variable_2="V"/>
<map_variables variable_1="i_Ca" variable_2="i_Ca"/>
<map_variables variable_1="i_Ca_K" variable_2="i_Ca_K"/>
<map_variables variable_1="R" variable_2="R"/>
<map_variables variable_1="T" variable_2="T"/>
<map_variables variable_1="F" variable_2="F"/>
<map_variables variable_1="C_sc" variable_2="C_sc"/>
</connection>
<connection>
<map_components component_1="membrane" component_2="intracellular_ion_concentrations"/>
<map_variables variable_1="F" variable_2="F"/>
<map_variables variable_1="C_sc" variable_2="C_sc"/>
</connection>
<connection>
<map_components component_1="fast_sodium_current" component_2="intracellular_ion_concentrations"/>
<map_variables variable_1="i_Na" variable_2="i_Na"/>
<map_variables variable_1="Na_i" variable_2="Na_i"/>
</connection>
<connection>
<map_components component_1="fast_sodium_current" component_2="sodium_background_current"/>
<map_variables variable_1="E_Na" variable_2="E_Na"/>
</connection>
<connection>
<map_components component_1="fast_sodium_current" component_2="extracellular_ion_concentrations"/>
<map_variables variable_1="Na_o" variable_2="Na_o"/>
</connection>
<connection>
<map_components component_1="intracellular_ion_concentrations" component_2="rapid_activating_delayed_rectifiyer_K_current"/>
<map_variables variable_1="i_Kr" variable_2="i_Kr"/>
<map_variables variable_1="K_i" variable_2="K_i"/>
</connection>
<connection>
<map_components component_1="extracellular_ion_concentrations" component_2="rapid_activating_delayed_rectifiyer_K_current"/>
<map_variables variable_1="K_o" variable_2="K_o"/>
</connection>
<connection>
<map_components component_1="transient_outward_potassium_current" component_2="rapid_activating_delayed_rectifiyer_K_current"/>
<map_variables variable_1="E_K" variable_2="E_K"/>
</connection>
<connection>
<map_components component_1="time_independent_potassium_current" component_2="rapid_activating_delayed_rectifiyer_K_current"/>
<map_variables variable_1="E_K" variable_2="E_K"/>
</connection>
<connection>
<map_components component_1="plateau_potassium_current" component_2="rapid_activating_delayed_rectifiyer_K_current"/>
<map_variables variable_1="E_K" variable_2="E_K"/>
</connection>
<connection>
<map_components component_1="intracellular_ion_concentrations" component_2="slow_activating_delayed_rectifiyer_K_current"/>
<map_variables variable_1="i_Ks" variable_2="i_Ks"/>
<map_variables variable_1="K_i" variable_2="K_i"/>
<map_variables variable_1="Na_i" variable_2="Na_i"/>
</connection>
<connection>
<map_components component_1="extracellular_ion_concentrations" component_2="slow_activating_delayed_rectifiyer_K_current"/>
<map_variables variable_1="K_o" variable_2="K_o"/>
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<connection>
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<connection>
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<connection>
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<connection>
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<connection>
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<connection>
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The University of Auckland, Auckland Bioengineering Institute
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Model study of ATP and ADP buffering, transport of Ca2+ and Mg2+, and regulation of ion pumps in ventricular myocyte
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This is the CellML description of Michailova and McCulloch's mathematical model of ATP and ADP buffering, transport of Ca and Mg, and regulation of ion pumps in ventricular myocytes.
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Michailova and McCulloch's mathematical model of ATP and ADP buffering, transport of Ca and Mg, and regulation of ion pumps in ventricular myocytes.
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