Location: Demir, Clark, Giles, Murphey, 1994 @ 807df612b0be / demir_clark_giles_murphey_1994.cellml

Author:
Tommy Yu <tommy.yu@auckland.ac.nz>
Date:
2010-08-26 12:15:21+12:00
Desc:
xml:base fix
Permanent Source URI:
http://models.cellml.org/workspace/demir_clark_giles_murphey_1994/rawfile/807df612b0beb0df80efcb9b0e9ce24598a0fb63/demir_clark_giles_murphey_1994.cellml

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<article>
  <articleinfo>
  <title>A Mathematical Model Of A Rabbit Sinoatrial Node Cell, 1994</title>
  <author>
    <firstname>Catherine</firstname>
          <surname>Lloyd</surname>
    <affiliation>
      <shortaffil>Bioengineering Institute, University of Auckland</shortaffil>
    </affiliation>
  </author>
</articleinfo>
  <section id="sec_status">
    <title>Model Status</title>
    <para>
      This version of the model has been curated by Penny Noble and is known to run in COR and PCEnv to replicate the published results.  Units have been checked and they are balanced.
</para>
  </section>
  <sect1 id="sec_structure">
<title>Model Structure</title>

<para>
ABSTRACT: A mathematical model for the electrophysiological responses of a rabbit sinoatrial node cell that is based on whole cell recordings from enzymatically isolated single pacemaker cells at 37 degrees C has been developed. The ion channels, Na(+)-K+ and Ca2+ pumps, and Na(+)-Ca2+ exchanger in the surface membrane (sarcolemma) are described using equations for these known currents in mammalian pacemaker cells. The extracellular environment is treated as a diffusion-limited space, and the myoplasm contains Ca(2+)-binding proteins (calmodulin and troponin). Original features of this model include 1) new equations for the hyperpolarization-activated inward current, 2) assessment of the role of the transient-type Ca2+ current during pacemaker depolarization, 3) inclusion of an Na+ current based on recent experimental data, and 4) demonstration of the possible influence of pump and exchanger currents and background currents on the pacemaker rate. This model provides acceptable fits to voltage-clamp and action potential data and can be used to seek biophysically based explanations of the electrophysiological activity in the rabbit sinoatrial node cell.
</para>

<para>
The original paper reference is cited below:
</para>

<para>
A mathematical model of a rabbit sinoatrial node cell, S.S. Demir, J.W. Clark, C.R. Murphey and W.R. Giles, 1994,
            <emphasis>American Journal of Physiology</emphasis>, 266, C832-C852.  <ulink url="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&amp;db=PubMed&amp;list_uids=8166247&amp;dopt=Abstract">PubMed ID: 8166247</ulink>
</para>

<informalfigure float="0" id="fig_cell_diagram">
<mediaobject>
  <imageobject>
    <objectinfo>
      <title>cell diagram of the Demir et al SAN model showing ionic currents, pumps and exchangers within the sarcolemma</title>
    </objectinfo>
    <imagedata fileref="demir_1994.png"/>
  </imageobject>
</mediaobject>
<caption>A schematic diagram describing the current flows across the cell membrane that are captured in the Demir <emphasis>et al</emphasis> 1994 model of the electrophysiological activity in a SA node cell.</caption>
</informalfigure>

</sect1>
</article>
</documentation>

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                           <minus/>
                           <ci>V</ci>
                           <cn xmlns:cellml="http://www.cellml.org/cellml/1.0#" cellml:units="millivolt">5</cn>
                        </apply>
                     </apply>
                  </apply>
                  <cn xmlns:cellml="http://www.cellml.org/cellml/1.0#" cellml:units="dimensionless">1</cn>
               </apply>
            </apply>
         </apply>
         <apply>
            <eq/>
            <ci>tau_d_L</ci>
            <apply>
               <divide/>
               <cn xmlns:cellml="http://www.cellml.org/cellml/1.0#" cellml:units="dimensionless">1</cn>
               <apply>
                  <plus/>
                  <ci>alpha_d_L</ci>
                  <ci>beta_d_L</ci>
               </apply>
            </apply>
         </apply>
         <apply>
            <eq/>
            <ci>d_L_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>
                           <plus/>
                           <ci>V</ci>
                           <cn xmlns:cellml="http://www.cellml.org/cellml/1.0#" cellml:units="millivolt">14.1</cn>
                        </apply>
                        <apply>
                           <minus/>
                           <cn xmlns:cellml="http://www.cellml.org/cellml/1.0#" cellml:units="millivolt">6</cn>
                        </apply>
                     </apply>
                  </apply>
               </apply>
            </apply>
         </apply>
         <apply>
            <eq/>
            <apply>
               <diff/>
               <bvar>
                  <ci>time</ci>
               </bvar>
               <ci>d_L</ci>
            </apply>
            <apply>
               <divide/>
               <apply>
                  <minus/>
                  <ci>d_L_infinity</ci>
                  <ci>d_L</ci>
               </apply>
               <ci>tau_d_L</ci>
            </apply>
         </apply>
      </math>
   </component>
   <component name="L_type_Ca_channel_f_gate">
      <variable initial_value="0.98651" name="f_L" public_interface="out" units="dimensionless"/>
      <variable name="alpha_f_L" units="per_second"/>
      <variable name="beta_f_L" units="per_second"/>
      <variable name="f_L_infinity" units="dimensionless"/>
      <variable name="tau_f_L" 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>alpha_f_L</ci>
            <apply>
               <divide/>
               <apply>
                  <times/>
                  <cn xmlns:cellml="http://www.cellml.org/cellml/1.0#" cellml:units="per_millivolt_second">3.75</cn>
                  <apply>
                     <plus/>
                     <ci>V</ci>
                     <cn xmlns:cellml="http://www.cellml.org/cellml/1.0#" cellml:units="millivolt">28</cn>
                  </apply>
               </apply>
               <apply>
                  <minus/>
                  <apply>
                     <exp/>
                     <apply>
                        <divide/>
                        <apply>
                           <plus/>
                           <ci>V</ci>
                           <cn xmlns:cellml="http://www.cellml.org/cellml/1.0#" cellml:units="millivolt">28</cn>
                        </apply>
                        <cn xmlns:cellml="http://www.cellml.org/cellml/1.0#" cellml:units="millivolt">4</cn>
                     </apply>
                  </apply>
                  <cn xmlns:cellml="http://www.cellml.org/cellml/1.0#" cellml:units="dimensionless">1</cn>
               </apply>
            </apply>
         </apply>
         <apply>
            <eq/>
            <ci>beta_f_L</ci>
            <apply>
               <divide/>
               <cn xmlns:cellml="http://www.cellml.org/cellml/1.0#" cellml:units="per_second">30</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">28</cn>
                        </apply>
                        <apply>
                           <minus/>
                           <cn xmlns:cellml="http://www.cellml.org/cellml/1.0#" cellml:units="millivolt">4</cn>
                        </apply>
                     </apply>
                  </apply>
               </apply>
            </apply>
         </apply>
         <apply>
            <eq/>
            <ci>tau_f_L</ci>
            <apply>
               <divide/>
               <cn xmlns:cellml="http://www.cellml.org/cellml/1.0#" cellml:units="dimensionless">1</cn>
               <apply>
                  <plus/>
                  <ci>alpha_f_L</ci>
                  <ci>beta_f_L</ci>
               </apply>
            </apply>
         </apply>
         <apply>
            <eq/>
            <ci>f_L_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>
                           <plus/>
                           <ci>V</ci>
                           <cn xmlns:cellml="http://www.cellml.org/cellml/1.0#" cellml:units="millivolt">30</cn>
                        </apply>
                        <cn xmlns:cellml="http://www.cellml.org/cellml/1.0#" cellml:units="millivolt">5</cn>
                     </apply>
                  </apply>
               </apply>
            </apply>
         </apply>
         <apply>
            <eq/>
            <apply>
               <diff/>
               <bvar>
                  <ci>time</ci>
               </bvar>
               <ci>f_L</ci>
            </apply>
            <apply>
               <divide/>
               <apply>
                  <minus/>
                  <ci>f_L_infinity</ci>
                  <ci>f_L</ci>
               </apply>
               <ci>tau_f_L</ci>
            </apply>
         </apply>
      </math>
   </component>
   <component name="T_type_Ca_channel">
      <variable name="i_Ca_T" public_interface="out" units="nanoA"/>
      <variable initial_value="0.02521" name="g_Ca_T" units="microS"/>
      <variable initial_value="45" name="E_Ca_T" 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="d_T" private_interface="in" units="dimensionless"/>
      <variable name="f_T" private_interface="in" units="dimensionless"/>
      <math xmlns="http://www.w3.org/1998/Math/MathML">
         <apply>
            <eq/>
            <ci>i_Ca_T</ci>
            <apply>
               <times/>
               <ci>g_Ca_T</ci>
               <ci>d_T</ci>
               <ci>f_T</ci>
               <apply>
                  <minus/>
                  <ci>V</ci>
                  <ci>E_Ca_T</ci>
               </apply>
            </apply>
         </apply>
      </math>
   </component>
   <component name="T_type_Ca_channel_d_gate">
      <variable initial_value="0.02012114" name="d_T" public_interface="out" units="dimensionless"/>
      <variable name="alpha_d_T" units="per_second"/>
      <variable name="beta_d_T" units="per_second"/>
      <variable name="d_T_infinity" units="dimensionless"/>
      <variable name="tau_d_T" 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>alpha_d_T</ci>
            <apply>
               <times/>
               <cn xmlns:cellml="http://www.cellml.org/cellml/1.0#" cellml:units="per_second">1068</cn>
               <apply>
                  <exp/>
                  <apply>
                     <divide/>
                     <apply>
                        <plus/>
                        <ci>V</ci>
                        <cn xmlns:cellml="http://www.cellml.org/cellml/1.0#" cellml:units="millivolt">26.3</cn>
                     </apply>
                     <cn xmlns:cellml="http://www.cellml.org/cellml/1.0#" cellml:units="millivolt">30</cn>
                  </apply>
               </apply>
            </apply>
         </apply>
         <apply>
            <eq/>
            <ci>beta_d_T</ci>
            <apply>
               <times/>
               <cn xmlns:cellml="http://www.cellml.org/cellml/1.0#" cellml:units="per_second">1068</cn>
               <apply>
                  <exp/>
                  <apply>
                     <divide/>
                     <apply>
                        <plus/>
                        <ci>V</ci>
                        <cn xmlns:cellml="http://www.cellml.org/cellml/1.0#" cellml:units="millivolt">26.3</cn>
                     </apply>
                     <apply>
                        <minus/>
                        <cn xmlns:cellml="http://www.cellml.org/cellml/1.0#" cellml:units="millivolt">30</cn>
                     </apply>
                  </apply>
               </apply>
            </apply>
         </apply>
         <apply>
            <eq/>
            <ci>tau_d_T</ci>
            <apply>
               <divide/>
               <cn xmlns:cellml="http://www.cellml.org/cellml/1.0#" cellml:units="dimensionless">1</cn>
               <apply>
                  <plus/>
                  <ci>alpha_d_T</ci>
                  <ci>beta_d_T</ci>
               </apply>
            </apply>
         </apply>
         <apply>
            <eq/>
            <ci>d_T_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>
                           <plus/>
                           <ci>V</ci>
                           <cn xmlns:cellml="http://www.cellml.org/cellml/1.0#" cellml:units="millivolt">26.3</cn>
                        </apply>
                        <apply>
                           <minus/>
                           <cn xmlns:cellml="http://www.cellml.org/cellml/1.0#" cellml:units="millivolt">6</cn>
                        </apply>
                     </apply>
                  </apply>
               </apply>
            </apply>
         </apply>
         <apply>
            <eq/>
            <apply>
               <diff/>
               <bvar>
                  <ci>time</ci>
               </bvar>
               <ci>d_T</ci>
            </apply>
            <apply>
               <divide/>
               <apply>
                  <minus/>
                  <ci>d_T_infinity</ci>
                  <ci>d_T</ci>
               </apply>
               <ci>tau_d_T</ci>
            </apply>
         </apply>
      </math>
   </component>
   <component name="T_type_Ca_channel_f_gate">
      <variable initial_value="0.1945111" name="f_T" public_interface="out" units="dimensionless"/>
      <variable name="alpha_f_T" units="per_second"/>
      <variable name="beta_f_T" units="per_second"/>
      <variable name="f_T_infinity" units="dimensionless"/>
      <variable name="tau_f_T" 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>alpha_f_T</ci>
            <apply>
               <times/>
               <cn xmlns:cellml="http://www.cellml.org/cellml/1.0#" cellml:units="per_second">15.3</cn>
               <apply>
                  <exp/>
                  <apply>
                     <divide/>
                     <apply>
                        <plus/>
                        <ci>V</ci>
                        <cn xmlns:cellml="http://www.cellml.org/cellml/1.0#" cellml:units="millivolt">61.7</cn>
                     </apply>
                     <apply>
                        <minus/>
                        <cn xmlns:cellml="http://www.cellml.org/cellml/1.0#" cellml:units="millivolt">83.3</cn>
                     </apply>
                  </apply>
               </apply>
            </apply>
         </apply>
         <apply>
            <eq/>
            <ci>beta_f_T</ci>
            <apply>
               <times/>
               <cn xmlns:cellml="http://www.cellml.org/cellml/1.0#" cellml:units="per_second">15</cn>
               <apply>
                  <exp/>
                  <apply>
                     <divide/>
                     <apply>
                        <plus/>
                        <ci>V</ci>
                        <cn xmlns:cellml="http://www.cellml.org/cellml/1.0#" cellml:units="millivolt">61.7</cn>
                     </apply>
                     <cn xmlns:cellml="http://www.cellml.org/cellml/1.0#" cellml:units="millivolt">15.38</cn>
                  </apply>
               </apply>
            </apply>
         </apply>
         <apply>
            <eq/>
            <ci>tau_f_T</ci>
            <apply>
               <divide/>
               <cn xmlns:cellml="http://www.cellml.org/cellml/1.0#" cellml:units="dimensionless">1</cn>
               <apply>
                  <plus/>
                  <ci>alpha_f_T</ci>
                  <ci>beta_f_T</ci>
               </apply>
            </apply>
         </apply>
         <apply>
            <eq/>
            <ci>f_T_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>
                           <plus/>
                           <ci>V</ci>
                           <cn xmlns:cellml="http://www.cellml.org/cellml/1.0#" cellml:units="millivolt">61.7</cn>
                        </apply>
                        <cn xmlns:cellml="http://www.cellml.org/cellml/1.0#" cellml:units="millivolt">5.6</cn>
                     </apply>
                  </apply>
               </apply>
            </apply>
         </apply>
         <apply>
            <eq/>
            <apply>
               <diff/>
               <bvar>
                  <ci>time</ci>
               </bvar>
               <ci>f_T</ci>
            </apply>
            <apply>
               <divide/>
               <apply>
                  <minus/>
                  <ci>f_T_infinity</ci>
                  <ci>f_T</ci>
               </apply>
               <ci>tau_f_T</ci>
            </apply>
         </apply>
      </math>
   </component>
   <component name="delayed_rectifying_potassium_current">
      <variable name="i_K" public_interface="out" units="nanoA"/>
      <variable name="g_K" units="microS"/>
      <variable name="E_K" public_interface="in" 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_b" public_interface="in" units="millimolar"/>
      <variable name="P_a" private_interface="in" units="dimensionless"/>
      <variable name="P_i" private_interface="in" units="dimensionless"/>
      <math xmlns="http://www.w3.org/1998/Math/MathML">
         <apply>
            <eq/>
            <ci>g_K</ci>
            <apply>
               <times/>
               <cn xmlns:cellml="http://www.cellml.org/cellml/1.0#" cellml:units="microS">0.00693</cn>
               <apply>
                  <power/>
                  <apply>
                     <divide/>
                     <ci>K_b</ci>
                     <cn xmlns:cellml="http://www.cellml.org/cellml/1.0#" cellml:units="millimolar">1</cn>
                  </apply>
                  <cn xmlns:cellml="http://www.cellml.org/cellml/1.0#" cellml:units="dimensionless">0.59</cn>
               </apply>
            </apply>
         </apply>
         <apply>
            <eq/>
            <ci>i_K</ci>
            <apply>
               <times/>
               <ci>g_K</ci>
               <ci>P_a</ci>
               <ci>P_i</ci>
               <apply>
                  <minus/>
                  <ci>V</ci>
                  <ci>E_K</ci>
               </apply>
            </apply>
         </apply>
      </math>
   </component>
   <component name="delayed_rectifying_potassium_current_P_a_gate">
      <variable initial_value="0.02302278" name="P_a" public_interface="out" units="dimensionless"/>
      <variable name="tau_P_a" units="second"/>
      <variable name="P_a_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>P_a_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>
                           <plus/>
                           <ci>V</ci>
                           <cn xmlns:cellml="http://www.cellml.org/cellml/1.0#" cellml:units="millivolt">5.1</cn>
                        </apply>
                        <apply>
                           <minus/>
                           <cn xmlns:cellml="http://www.cellml.org/cellml/1.0#" cellml:units="millivolt">7.4</cn>
                        </apply>
                     </apply>
                  </apply>
               </apply>
            </apply>
         </apply>
         <apply>
            <eq/>
            <ci>tau_P_a</ci>
            <apply>
               <divide/>
               <cn xmlns:cellml="http://www.cellml.org/cellml/1.0#" cellml:units="second">1</cn>
               <apply>
                  <plus/>
                  <apply>
                     <times/>
                     <cn xmlns:cellml="http://www.cellml.org/cellml/1.0#" cellml:units="dimensionless">17</cn>
                     <apply>
                        <exp/>
                        <apply>
                           <times/>
                           <cn xmlns:cellml="http://www.cellml.org/cellml/1.0#" cellml:units="per_millivolt">0.0398</cn>
                           <ci>V</ci>
                        </apply>
                     </apply>
                  </apply>
                  <apply>
                     <times/>
                     <cn xmlns:cellml="http://www.cellml.org/cellml/1.0#" cellml:units="dimensionless">2.11</cn>
                     <apply>
                        <exp/>
                        <apply>
                           <times/>
                           <apply>
                              <minus/>
                              <cn xmlns:cellml="http://www.cellml.org/cellml/1.0#" cellml:units="per_millivolt">0.051</cn>
                           </apply>
                           <ci>V</ci>
                        </apply>
                     </apply>
                  </apply>
               </apply>
            </apply>
         </apply>
         <apply>
            <eq/>
            <apply>
               <diff/>
               <bvar>
                  <ci>time</ci>
               </bvar>
               <ci>P_a</ci>
            </apply>
            <apply>
               <divide/>
               <apply>
                  <minus/>
                  <ci>P_a_infinity</ci>
                  <ci>P_a</ci>
               </apply>
               <ci>tau_P_a</ci>
            </apply>
         </apply>
      </math>
   </component>
   <component name="delayed_rectifying_potassium_current_P_i_gate">
      <variable initial_value="0.3777728" name="P_i" public_interface="out" units="dimensionless"/>
      <variable name="alpha_P_i" units="per_second"/>
      <variable name="beta_P_i" 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_P_i</ci>
            <apply>
               <times/>
               <cn xmlns:cellml="http://www.cellml.org/cellml/1.0#" cellml:units="per_second">100</cn>
               <apply>
                  <exp/>
                  <apply>
                     <times/>
                     <apply>
                        <minus/>
                        <cn xmlns:cellml="http://www.cellml.org/cellml/1.0#" cellml:units="per_millivolt">0.0183</cn>
                     </apply>
                     <ci>V</ci>
                  </apply>
               </apply>
            </apply>
         </apply>
         <apply>
            <eq/>
            <ci>beta_P_i</ci>
            <apply>
               <times/>
               <cn xmlns:cellml="http://www.cellml.org/cellml/1.0#" cellml:units="per_second">656</cn>
               <apply>
                  <exp/>
                  <apply>
                     <times/>
                     <cn xmlns:cellml="http://www.cellml.org/cellml/1.0#" cellml:units="per_millivolt">0.00942</cn>
                     <ci>V</ci>
                  </apply>
               </apply>
            </apply>
         </apply>
         <apply>
            <eq/>
            <apply>
               <diff/>
               <bvar>
                  <ci>time</ci>
               </bvar>
               <ci>P_i</ci>
            </apply>
            <apply>
               <minus/>
               <apply>
                  <times/>
                  <ci>alpha_P_i</ci>
                  <apply>
                     <minus/>
                     <cn xmlns:cellml="http://www.cellml.org/cellml/1.0#" cellml:units="dimensionless">1</cn>
                     <ci>P_i</ci>
                  </apply>
               </apply>
               <apply>
                  <times/>
                  <ci>beta_P_i</ci>
                  <ci>P_i</ci>
               </apply>
            </apply>
         </apply>
      </math>
   </component>
   <component name="linear_background_current">
      <variable name="i_B" public_interface="out" units="nanoA"/>
      <variable name="i_B_Na" public_interface="out" units="nanoA"/>
      <variable name="i_B_Ca" public_interface="out" units="nanoA"/>
      <variable name="i_B_K" public_interface="out" units="nanoA"/>
      <variable initial_value="0.00016" name="g_B_Na" units="microS"/>
      <variable initial_value="0.0000364" name="g_B_Ca" units="microS"/>
      <variable initial_value="0.0000694" name="g_B_K" units="microS"/>
      <variable name="E_Na" public_interface="in" units="millivolt"/>
      <variable name="E_Ca" public_interface="in" units="millivolt"/>
      <variable name="E_K" public_interface="in" units="millivolt"/>
      <variable name="time" public_interface="in" units="second"/>
      <variable name="V" public_interface="in" units="millivolt"/>
      <math xmlns="http://www.w3.org/1998/Math/MathML">
         <apply>
            <eq/>
            <ci>i_B_Na</ci>
            <apply>
               <times/>
               <ci>g_B_Na</ci>
               <apply>
                  <minus/>
                  <ci>V</ci>
                  <ci>E_Na</ci>
               </apply>
            </apply>
         </apply>
         <apply>
            <eq/>
            <ci>i_B_Ca</ci>
            <apply>
               <times/>
               <ci>g_B_Ca</ci>
               <apply>
                  <minus/>
                  <ci>V</ci>
                  <ci>E_Ca</ci>
               </apply>
            </apply>
         </apply>
         <apply>
            <eq/>
            <ci>i_B_K</ci>
            <apply>
               <times/>
               <ci>g_B_K</ci>
               <apply>
                  <minus/>
                  <ci>V</ci>
                  <ci>E_K</ci>
               </apply>
            </apply>
         </apply>
         <apply>
            <eq/>
            <ci>i_B</ci>
            <apply>
               <plus/>
               <ci>i_B_Na</ci>
               <ci>i_B_Ca</ci>
               <ci>i_B_K</ci>
            </apply>
         </apply>
      </math>
   </component>
   <component name="hyperpolarisation_activated_current">
      <variable name="i_f" public_interface="out" units="nanoA"/>
      <variable name="i_f_Na" public_interface="out" units="nanoA"/>
      <variable name="i_f_K" public_interface="out" units="nanoA"/>
      <variable initial_value="0.0067478" name="g_f_Na" units="microS"/>
      <variable initial_value="0.0128821" name="g_f_K" units="microS"/>
      <variable name="time" private_interface="out" public_interface="in" units="second"/>
      <variable name="V" private_interface="out" public_interface="in" units="millivolt"/>
      <variable name="y" private_interface="in" units="dimensionless"/>
      <math xmlns="http://www.w3.org/1998/Math/MathML">
         <apply>
            <eq/>
            <ci>i_f_Na</ci>
            <apply>
               <times/>
               <ci>g_f_Na</ci>
               <apply>
                  <power/>
                  <ci>y</ci>
                  <cn xmlns:cellml="http://www.cellml.org/cellml/1.0#" cellml:units="dimensionless">2</cn>
               </apply>
               <apply>
                  <minus/>
                  <ci>V</ci>
                  <cn xmlns:cellml="http://www.cellml.org/cellml/1.0#" cellml:units="millivolt">75</cn>
               </apply>
            </apply>
         </apply>
         <apply>
            <eq/>
            <ci>i_f_K</ci>
            <apply>
               <times/>
               <ci>g_f_K</ci>
               <apply>
                  <power/>
                  <ci>y</ci>
                  <cn xmlns:cellml="http://www.cellml.org/cellml/1.0#" cellml:units="dimensionless">2</cn>
               </apply>
               <apply>
                  <plus/>
                  <ci>V</ci>
                  <cn xmlns:cellml="http://www.cellml.org/cellml/1.0#" cellml:units="millivolt">85</cn>
               </apply>
            </apply>
         </apply>
         <apply>
            <eq/>
            <ci>i_f</ci>
            <apply>
               <plus/>
               <ci>i_f_Na</ci>
               <ci>i_f_K</ci>
            </apply>
         </apply>
      </math>
   </component>
   <component name="hyperpolarisation_activated_current_y_gate">
      <variable initial_value="0.09227776" 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>
               <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>
                           <plus/>
                           <ci>V</ci>
                           <cn xmlns:cellml="http://www.cellml.org/cellml/1.0#" cellml:units="millivolt">72.2</cn>
                        </apply>
                        <cn xmlns:cellml="http://www.cellml.org/cellml/1.0#" cellml:units="millivolt">9</cn>
                     </apply>
                  </apply>
               </apply>
            </apply>
         </apply>
         <apply>
            <eq/>
            <ci>tau_y</ci>
            <apply>
               <divide/>
               <cn xmlns:cellml="http://www.cellml.org/cellml/1.0#" cellml:units="second">1</cn>
               <apply>
                  <plus/>
                  <apply>
                     <times/>
                     <cn xmlns:cellml="http://www.cellml.org/cellml/1.0#" cellml:units="dimensionless">1.6483</cn>
                     <apply>
                        <exp/>
                        <apply>
                           <divide/>
                           <apply>
                              <plus/>
                              <ci>V</ci>
                              <cn xmlns:cellml="http://www.cellml.org/cellml/1.0#" cellml:units="millivolt">54.06</cn>
                           </apply>
                           <apply>
                              <minus/>
                              <cn xmlns:cellml="http://www.cellml.org/cellml/1.0#" cellml:units="millivolt">24.33</cn>
                           </apply>
                        </apply>
                     </apply>
                  </apply>
                  <apply>
                     <divide/>
                     <cn xmlns:cellml="http://www.cellml.org/cellml/1.0#" cellml:units="dimensionless">14.01055</cn>
                     <apply>
                        <plus/>
                        <cn xmlns:cellml="http://www.cellml.org/cellml/1.0#" cellml:units="dimensionless">0.7</cn>
                        <apply>
                           <exp/>
                           <apply>
                              <divide/>
                              <apply>
                                 <plus/>
                                 <ci>V</ci>
                                 <cn xmlns:cellml="http://www.cellml.org/cellml/1.0#" cellml:units="millivolt">60</cn>
                              </apply>
                              <apply>
                                 <minus/>
                                 <cn xmlns:cellml="http://www.cellml.org/cellml/1.0#" cellml:units="millivolt">5.5</cn>
                              </apply>
                           </apply>
                        </apply>
                     </apply>
                  </apply>
               </apply>
            </apply>
         </apply>
         <apply>
            <eq/>
            <apply>
               <diff/>
               <bvar>
                  <ci>time</ci>
               </bvar>
               <ci>y</ci>
            </apply>
            <apply>
               <divide/>
               <apply>
                  <minus/>
                  <ci>y_infinity</ci>
                  <ci>y</ci>
               </apply>
               <ci>tau_y</ci>
            </apply>
         </apply>
      </math>
   </component>
   <component name="sodium_potassium_pump">
      <variable name="i_NaK" public_interface="out" units="nanoA"/>
      <variable initial_value="5.46" name="K_m_Na" units="millimolar"/>
      <variable initial_value="0.621" name="K_m_K" units="millimolar"/>
      <variable initial_value="0.2192" name="i_NaK_max" units="nanoA"/>
      <variable name="Na_i" public_interface="in" units="millimolar"/>
      <variable name="K_c" public_interface="in" units="millimolar"/>
      <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>i_NaK</ci>
            <apply>
               <divide/>
               <apply>
                  <times/>
                  <ci>i_NaK_max</ci>
                  <apply>
                     <power/>
                     <apply>
                        <divide/>
                        <ci>Na_i</ci>
                        <apply>
                           <plus/>
                           <ci>K_m_Na</ci>
                           <ci>Na_i</ci>
                        </apply>
                     </apply>
                     <cn xmlns:cellml="http://www.cellml.org/cellml/1.0#" cellml:units="dimensionless">3</cn>
                  </apply>
                  <apply>
                     <power/>
                     <apply>
                        <divide/>
                        <ci>K_c</ci>
                        <apply>
                           <plus/>
                           <ci>K_m_K</ci>
                           <ci>K_c</ci>
                        </apply>
                     </apply>
                     <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">1.6</cn>
               </apply>
               <apply>
                  <plus/>
                  <cn xmlns:cellml="http://www.cellml.org/cellml/1.0#" cellml:units="dimensionless">1.5</cn>
                  <apply>
                     <exp/>
                     <apply>
                        <divide/>
                        <apply>
                           <plus/>
                           <ci>V</ci>
                           <cn xmlns:cellml="http://www.cellml.org/cellml/1.0#" cellml:units="millivolt">60</cn>
                        </apply>
                        <apply>
                           <minus/>
                           <cn xmlns:cellml="http://www.cellml.org/cellml/1.0#" cellml:units="millivolt">40</cn>
                        </apply>
                     </apply>
                  </apply>
               </apply>
            </apply>
         </apply>
      </math>
   </component>
   <component name="calcium_pump_current">
      <variable name="i_Ca_P" public_interface="out" units="nanoA"/>
      <variable initial_value="0.02869" name="i_Ca_P_max" units="nanoA"/>
      <variable name="Ca_i" public_interface="in" units="millimolar"/>
      <variable name="time" public_interface="in" units="second"/>
      <math xmlns="http://www.w3.org/1998/Math/MathML">
         <apply>
            <eq/>
            <ci>i_Ca_P</ci>
            <apply>
               <divide/>
               <apply>
                  <times/>
                  <ci>i_Ca_P_max</ci>
                  <ci>Ca_i</ci>
               </apply>
               <apply>
                  <plus/>
                  <ci>Ca_i</ci>
                  <cn xmlns:cellml="http://www.cellml.org/cellml/1.0#" cellml:units="millimolar">0.0004</cn>
               </apply>
            </apply>
         </apply>
      </math>
   </component>
   <component name="sodium_calcium_pump">
      <variable name="i_NaCa" public_interface="out" units="nanoA"/>
      <variable initial_value="0.00001248" name="K_NaCa" units="nanoA"/>
      <variable initial_value="0.0001" name="d_NaCa" units="dimensionless"/>
      <variable initial_value="0.5" name="gamma" units="dimensionless"/>
      <variable name="Na_i" public_interface="in" units="millimolar"/>
      <variable name="Na_c" public_interface="in" units="millimolar"/>
      <variable name="Ca_i" public_interface="in" units="millimolar"/>
      <variable name="Ca_c" public_interface="in" units="millimolar"/>
      <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>i_NaCa</ci>
            <apply>
               <divide/>
               <apply>
                  <times/>
                  <ci>K_NaCa</ci>
                  <apply>
                     <minus/>
                     <apply>
                        <times/>
                        <apply>
                           <power/>
                           <ci>Na_i</ci>
                           <cn xmlns:cellml="http://www.cellml.org/cellml/1.0#" cellml:units="dimensionless">3</cn>
                        </apply>
                        <ci>Ca_c</ci>
                        <apply>
                           <exp/>
                           <apply>
                              <times/>
                              <cn xmlns:cellml="http://www.cellml.org/cellml/1.0#" cellml:units="per_millivolt">0.03743</cn>
                              <ci>V</ci>
                              <ci>gamma</ci>
                           </apply>
                        </apply>
                     </apply>
                     <apply>
                        <times/>
                        <apply>
                           <power/>
                           <ci>Na_c</ci>
                           <cn xmlns:cellml="http://www.cellml.org/cellml/1.0#" cellml:units="dimensionless">3</cn>
                        </apply>
                        <ci>Ca_i</ci>
                        <apply>
                           <exp/>
                           <apply>
                              <times/>
                              <cn xmlns:cellml="http://www.cellml.org/cellml/1.0#" cellml:units="per_millivolt">0.03743</cn>
                              <ci>V</ci>
                              <apply>
                                 <minus/>
                                 <ci>gamma</ci>
                                 <cn xmlns:cellml="http://www.cellml.org/cellml/1.0#" cellml:units="dimensionless">1</cn>
                              </apply>
                           </apply>
                        </apply>
                     </apply>
                  </apply>
               </apply>
               <apply>
                  <plus/>
                  <cn xmlns:cellml="http://www.cellml.org/cellml/1.0#" cellml:units="millimolar4">1</cn>
                  <apply>
                     <times/>
                     <ci>d_NaCa</ci>
                     <apply>
                        <plus/>
                        <apply>
                           <times/>
                           <ci>Ca_i</ci>
                           <apply>
                              <power/>
                              <ci>Na_c</ci>
                              <cn xmlns:cellml="http://www.cellml.org/cellml/1.0#" cellml:units="dimensionless">3</cn>
                           </apply>
                        </apply>
                        <apply>
                           <times/>
                           <ci>Ca_c</ci>
                           <apply>
                              <power/>
                              <ci>Na_i</ci>
                              <cn xmlns:cellml="http://www.cellml.org/cellml/1.0#" cellml:units="dimensionless">3</cn>
                           </apply>
                        </apply>
                     </apply>
                  </apply>
               </apply>
            </apply>
         </apply>
      </math>
   </component>
   <component name="intracellular_concentrations_and_buffer_equations">
      <variable cmeta:id="intracellular_concentrations_and_buffer_equations_Na_i" initial_value="9.701621" name="Na_i" public_interface="out" units="millimolar"/>
      <variable cmeta:id="intracellular_concentrations_and_buffer_equations_Ca_i" initial_value="3.787018e-4" name="Ca_i" public_interface="out" units="millimolar"/>
      <variable cmeta:id="intracellular_concentrations_and_buffer_equations_K_i" initial_value="1.407347e2" name="K_i" public_interface="out" units="millimolar"/>
      <variable cmeta:id="intracellular_concentrations_and_buffer_equations_Ca_Calmod" initial_value="0.1411678" name="Ca_Calmod" units="dimensionless"/>
      <variable cmeta:id="intracellular_concentrations_and_buffer_equations_Ca_Trop" initial_value="0.07331396" name="Ca_Trop" units="dimensionless"/>
      <variable initial_value="0.7618549" name="Ca_Mg_Trop" units="dimensionless"/>
      <variable initial_value="0.2097049" name="Mg_Mg_Trop" units="dimensionless"/>
      <variable name="phi_C" units="per_second"/>
      <variable name="phi_TC" units="per_second"/>
      <variable name="phi_TMgC" units="per_second"/>
      <variable name="phi_TMgM" units="per_second"/>
      <variable name="phi_B" units="millimolar_per_second"/>
      <variable initial_value="2.5" name="Mg_i" units="millimolar"/>
      <variable name="F_C" units="millimolar_per_second"/>
      <variable name="F_TC" units="millimolar_per_second"/>
      <variable name="F_TMgC" units="millimolar_per_second"/>
      <variable name="Vol" public_interface="in" units="microLitre"/>
      <variable name="V_i" public_interface="out" units="microLitre"/>
      <variable name="i_NaK" public_interface="in" units="nanoA"/>
      <variable name="i_NaCa" public_interface="in" units="nanoA"/>
      <variable name="i_B_Na" public_interface="in" units="nanoA"/>
      <variable name="i_f_Na" public_interface="in" units="nanoA"/>
      <variable name="i_Na" public_interface="in" units="nanoA"/>
      <variable name="i_K" public_interface="in" units="nanoA"/>
      <variable name="i_B_K" public_interface="in" units="nanoA"/>
      <variable name="i_f_K" public_interface="in" units="nanoA"/>
      <variable name="i_Ca_L" public_interface="in" units="nanoA"/>
      <variable name="i_Ca_T" public_interface="in" units="nanoA"/>
      <variable name="i_Ca_P" public_interface="in" units="nanoA"/>
      <variable name="i_B_Ca" public_interface="in" units="nanoA"/>
      <variable name="i_up" public_interface="in" units="nanoA"/>
      <variable name="i_rel" public_interface="in" units="nanoA"/>
      <variable name="F" public_interface="in" units="coulomb_per_mole"/>
      <variable name="time" public_interface="in" units="second"/>
      <math xmlns="http://www.w3.org/1998/Math/MathML">
         <apply>
            <eq/>
            <ci>V_i</ci>
            <apply>
               <times/>
               <cn xmlns:cellml="http://www.cellml.org/cellml/1.0#" cellml:units="dimensionless">0.465</cn>
               <ci>Vol</ci>
            </apply>
         </apply>
         <apply>
            <eq/>
            <ci>phi_C</ci>
            <apply>
               <minus/>
               <apply>
                  <times/>
                  <cn xmlns:cellml="http://www.cellml.org/cellml/1.0#" cellml:units="per_millimolar_second">129000</cn>
                  <ci>Ca_i</ci>
                  <apply>
                     <minus/>
                     <cn xmlns:cellml="http://www.cellml.org/cellml/1.0#" cellml:units="dimensionless">1</cn>
                     <ci>Ca_Calmod</ci>
                  </apply>
               </apply>
               <apply>
                  <times/>
                  <cn xmlns:cellml="http://www.cellml.org/cellml/1.0#" cellml:units="per_second">307</cn>
                  <ci>Ca_Calmod</ci>
               </apply>
            </apply>
         </apply>
         <apply>
            <eq/>
            <apply>
               <diff/>
               <bvar>
                  <ci>time</ci>
               </bvar>
               <ci>Ca_Calmod</ci>
            </apply>
            <ci>phi_C</ci>
         </apply>
         <apply>
            <eq/>
            <ci>phi_TC</ci>
            <apply>
               <minus/>
               <apply>
                  <times/>
                  <cn xmlns:cellml="http://www.cellml.org/cellml/1.0#" cellml:units="per_millimolar_second">50500</cn>
                  <ci>Ca_i</ci>
                  <apply>
                     <minus/>
                     <cn xmlns:cellml="http://www.cellml.org/cellml/1.0#" cellml:units="dimensionless">1</cn>
                     <ci>Ca_Trop</ci>
                  </apply>
               </apply>
               <apply>
                  <times/>
                  <cn xmlns:cellml="http://www.cellml.org/cellml/1.0#" cellml:units="per_second">252</cn>
                  <ci>Ca_Trop</ci>
               </apply>
            </apply>
         </apply>
         <apply>
            <eq/>
            <apply>
               <diff/>
               <bvar>
                  <ci>time</ci>
               </bvar>
               <ci>Ca_Trop</ci>
            </apply>
            <ci>phi_TC</ci>
         </apply>
         <apply>
            <eq/>
            <ci>phi_TMgC</ci>
            <apply>
               <minus/>
               <apply>
                  <times/>
                  <cn xmlns:cellml="http://www.cellml.org/cellml/1.0#" cellml:units="per_millimolar_second">129000</cn>
                  <ci>Ca_i</ci>
                  <apply>
                     <minus/>
                     <cn xmlns:cellml="http://www.cellml.org/cellml/1.0#" cellml:units="dimensionless">1</cn>
                     <apply>
                        <plus/>
                        <ci>Ca_Mg_Trop</ci>
                        <ci>Mg_Mg_Trop</ci>
                     </apply>
                  </apply>
               </apply>
               <apply>
                  <times/>
                  <cn xmlns:cellml="http://www.cellml.org/cellml/1.0#" cellml:units="per_second">4.25</cn>
                  <ci>Ca_Mg_Trop</ci>
               </apply>
            </apply>
         </apply>
         <apply>
            <eq/>
            <apply>
               <diff/>
               <bvar>
                  <ci>time</ci>
               </bvar>
               <ci>Ca_Mg_Trop</ci>
            </apply>
            <ci>phi_TMgC</ci>
         </apply>
         <apply>
            <eq/>
            <ci>phi_TMgM</ci>
            <apply>
               <minus/>
               <apply>
                  <times/>
                  <cn xmlns:cellml="http://www.cellml.org/cellml/1.0#" cellml:units="per_millimolar_second">1290</cn>
                  <ci>Mg_i</ci>
                  <apply>
                     <minus/>
                     <cn xmlns:cellml="http://www.cellml.org/cellml/1.0#" cellml:units="dimensionless">1</cn>
                     <apply>
                        <plus/>
                        <ci>Ca_Mg_Trop</ci>
                        <ci>Mg_Mg_Trop</ci>
                     </apply>
                  </apply>
               </apply>
               <apply>
                  <times/>
                  <cn xmlns:cellml="http://www.cellml.org/cellml/1.0#" cellml:units="per_second">429</cn>
                  <ci>Mg_Mg_Trop</ci>
               </apply>
            </apply>
         </apply>
         <apply>
            <eq/>
            <apply>
               <diff/>
               <bvar>
                  <ci>time</ci>
               </bvar>
               <ci>Mg_Mg_Trop</ci>
            </apply>
            <ci>phi_TMgM</ci>
         </apply>
         <apply>
            <eq/>
            <ci>F_C</ci>
            <apply>
               <times/>
               <cn xmlns:cellml="http://www.cellml.org/cellml/1.0#" cellml:units="millimolar">0.09</cn>
               <ci>phi_C</ci>
            </apply>
         </apply>
         <apply>
            <eq/>
            <ci>F_TC</ci>
            <apply>
               <times/>
               <cn xmlns:cellml="http://www.cellml.org/cellml/1.0#" cellml:units="millimolar">0.031</cn>
               <ci>phi_TC</ci>
            </apply>
         </apply>
         <apply>
            <eq/>
            <ci>F_TMgC</ci>
            <apply>
               <times/>
               <cn xmlns:cellml="http://www.cellml.org/cellml/1.0#" cellml:units="millimolar">0.062</cn>
               <ci>phi_TMgC</ci>
            </apply>
         </apply>
         <apply>
            <eq/>
            <ci>phi_B</ci>
            <apply>
               <plus/>
               <ci>F_C</ci>
               <ci>F_TC</ci>
               <ci>F_TMgC</ci>
            </apply>
         </apply>
         <apply>
            <eq/>
            <apply>
               <diff/>
               <bvar>
                  <ci>time</ci>
               </bvar>
               <ci>Na_i</ci>
            </apply>
            <apply>
               <divide/>
               <apply>
                  <minus/>
                  <apply>
                     <plus/>
                     <apply>
                        <times/>
                        <cn xmlns:cellml="http://www.cellml.org/cellml/1.0#" cellml:units="dimensionless">3</cn>
                        <ci>i_NaK</ci>
                     </apply>
                     <apply>
                        <times/>
                        <cn xmlns:cellml="http://www.cellml.org/cellml/1.0#" cellml:units="dimensionless">3</cn>
                        <ci>i_NaCa</ci>
                     </apply>
                     <ci>i_B_Na</ci>
                     <ci>i_f_Na</ci>
                     <ci>i_Na</ci>
                  </apply>
               </apply>
               <apply>
                  <times/>
                  <ci>F</ci>
                  <ci>V_i</ci>
               </apply>
            </apply>
         </apply>
         <apply>
            <eq/>
            <apply>
               <diff/>
               <bvar>
                  <ci>time</ci>
               </bvar>
               <ci>K_i</ci>
            </apply>
            <apply>
               <divide/>
               <apply>
                  <minus/>
                  <apply>
                     <times/>
                     <cn xmlns:cellml="http://www.cellml.org/cellml/1.0#" cellml:units="dimensionless">2</cn>
                     <ci>i_NaK</ci>
                  </apply>
                  <apply>
                     <plus/>
                     <ci>i_K</ci>
                     <ci>i_f_K</ci>
                     <ci>i_B_K</ci>
                  </apply>
               </apply>
               <apply>
                  <times/>
                  <ci>F</ci>
                  <ci>V_i</ci>
               </apply>
            </apply>
         </apply>
         <apply>
            <eq/>
            <apply>
               <diff/>
               <bvar>
                  <ci>time</ci>
               </bvar>
               <ci>Ca_i</ci>
            </apply>
            <apply>
               <minus/>
               <apply>
                  <divide/>
                  <apply>
                     <minus/>
                     <apply>
                        <plus/>
                        <apply>
                           <times/>
                           <cn xmlns:cellml="http://www.cellml.org/cellml/1.0#" cellml:units="dimensionless">2</cn>
                           <ci>i_NaCa</ci>
                        </apply>
                        <ci>i_rel</ci>
                     </apply>
                     <apply>
                        <plus/>
                        <ci>i_Ca_L</ci>
                        <ci>i_Ca_T</ci>
                        <ci>i_Ca_P</ci>
                        <ci>i_B_Ca</ci>
                        <ci>i_up</ci>
                     </apply>
                  </apply>
                  <apply>
                     <times/>
                     <cn xmlns:cellml="http://www.cellml.org/cellml/1.0#" cellml:units="dimensionless">2</cn>
                     <ci>V_i</ci>
                     <ci>F</ci>
                  </apply>
               </apply>
               <ci>phi_B</ci>
            </apply>
         </apply>
      </math>
   </component>
   <component name="cleft_space_equations">
      <variable cmeta:id="cleft_space_equations_Na_c" initial_value="139.9988" name="Na_c" public_interface="out" units="millimolar"/>
      <variable cmeta:id="cleft_space_equations_Ca_c" initial_value="2.00474" name="Ca_c" public_interface="out" units="millimolar"/>
      <variable cmeta:id="cleft_space_equations_K_c" initial_value="5.389014" name="K_c" public_interface="out" units="millimolar"/>
      <variable initial_value="5.4" name="K_b" public_interface="out" units="millimolar"/>
      <variable initial_value="140" name="Na_b" units="millimolar"/>
      <variable initial_value="2" name="Ca_b" units="millimolar"/>
      <variable initial_value="3.497e-6" name="Vol" public_interface="out" units="microLitre"/>
      <variable name="V_c" units="microLitre"/>
      <variable initial_value="0.01" name="tau_p" units="second"/>
      <variable name="i_NaK" public_interface="in" units="nanoA"/>
      <variable name="i_NaCa" public_interface="in" units="nanoA"/>
      <variable name="i_B_Na" public_interface="in" units="nanoA"/>
      <variable name="i_f_Na" public_interface="in" units="nanoA"/>
      <variable name="i_Na" public_interface="in" units="nanoA"/>
      <variable name="i_K" public_interface="in" units="nanoA"/>
      <variable name="i_B_K" public_interface="in" units="nanoA"/>
      <variable name="i_f_K" public_interface="in" units="nanoA"/>
      <variable name="i_Ca_L" public_interface="in" units="nanoA"/>
      <variable name="i_Ca_T" public_interface="in" units="nanoA"/>
      <variable name="i_Ca_P" public_interface="in" units="nanoA"/>
      <variable name="i_B_Ca" public_interface="in" units="nanoA"/>
      <variable name="F" public_interface="in" units="coulomb_per_mole"/>
      <variable name="time" public_interface="in" units="second"/>
      <math xmlns="http://www.w3.org/1998/Math/MathML">
         <apply>
            <eq/>
            <ci>V_c</ci>
            <apply>
               <times/>
               <cn xmlns:cellml="http://www.cellml.org/cellml/1.0#" cellml:units="dimensionless">0.136</cn>
               <ci>Vol</ci>
            </apply>
         </apply>
         <apply>
            <eq/>
            <apply>
               <diff/>
               <bvar>
                  <ci>time</ci>
               </bvar>
               <ci>Na_c</ci>
            </apply>
            <apply>
               <plus/>
               <apply>
                  <divide/>
                  <apply>
                     <minus/>
                     <ci>Na_b</ci>
                     <ci>Na_c</ci>
                  </apply>
                  <ci>tau_p</ci>
               </apply>
               <apply>
                  <divide/>
                  <apply>
                     <plus/>
                     <ci>i_Na</ci>
                     <apply>
                        <times/>
                        <cn xmlns:cellml="http://www.cellml.org/cellml/1.0#" cellml:units="dimensionless">3</cn>
                        <ci>i_NaCa</ci>
                     </apply>
                     <apply>
                        <times/>
                        <cn xmlns:cellml="http://www.cellml.org/cellml/1.0#" cellml:units="dimensionless">3</cn>
                        <ci>i_NaK</ci>
                     </apply>
                     <ci>i_B_Na</ci>
                     <ci>i_f_Na</ci>
                  </apply>
                  <apply>
                     <times/>
                     <ci>F</ci>
                     <ci>V_c</ci>
                  </apply>
               </apply>
            </apply>
         </apply>
         <apply>
            <eq/>
            <apply>
               <diff/>
               <bvar>
                  <ci>time</ci>
               </bvar>
               <ci>K_c</ci>
            </apply>
            <apply>
               <plus/>
               <apply>
                  <divide/>
                  <apply>
                     <minus/>
                     <ci>K_b</ci>
                     <ci>K_c</ci>
                  </apply>
                  <ci>tau_p</ci>
               </apply>
               <apply>
                  <divide/>
                  <apply>
                     <plus/>
                     <apply>
                        <times/>
                        <apply>
                           <minus/>
                           <cn xmlns:cellml="http://www.cellml.org/cellml/1.0#" cellml:units="dimensionless">2</cn>
                        </apply>
                        <ci>i_NaK</ci>
                     </apply>
                     <ci>i_K</ci>
                     <ci>i_B_K</ci>
                     <ci>i_f_K</ci>
                  </apply>
                  <apply>
                     <times/>
                     <ci>F</ci>
                     <ci>V_c</ci>
                  </apply>
               </apply>
            </apply>
         </apply>
         <apply>
            <eq/>
            <apply>
               <diff/>
               <bvar>
                  <ci>time</ci>
               </bvar>
               <ci>Ca_c</ci>
            </apply>
            <apply>
               <plus/>
               <apply>
                  <divide/>
                  <apply>
                     <minus/>
                     <ci>Ca_b</ci>
                     <ci>Ca_c</ci>
                  </apply>
                  <ci>tau_p</ci>
               </apply>
               <apply>
                  <divide/>
                  <apply>
                     <plus/>
                     <apply>
                        <times/>
                        <apply>
                           <minus/>
                           <cn xmlns:cellml="http://www.cellml.org/cellml/1.0#" cellml:units="dimensionless">2</cn>
                        </apply>
                        <ci>i_NaCa</ci>
                     </apply>
                     <ci>i_Ca_L</ci>
                     <ci>i_Ca_T</ci>
                     <ci>i_Ca_P</ci>
                     <ci>i_B_Ca</ci>
                  </apply>
                  <apply>
                     <times/>
                     <cn xmlns:cellml="http://www.cellml.org/cellml/1.0#" cellml:units="dimensionless">2</cn>
                     <ci>F</ci>
                     <ci>V_c</ci>
                  </apply>
               </apply>
            </apply>
         </apply>
      </math>
   </component>
   <component name="SR_Ca_uptake_and_release">
      <variable cmeta:id="SR_Ca_uptake_and_release_i_rel" name="i_rel" public_interface="out" units="nanoA"/>
      <variable cmeta:id="SR_Ca_uptake_and_release_i_up" name="i_up" public_interface="out" units="nanoA"/>
      <variable cmeta:id="SR_Ca_uptake_and_release_i_tr" name="i_tr" units="nanoA"/>
      <variable initial_value="16.95311" name="Ca_up" units="millimolar"/>
      <variable initial_value="16.85024" name="Ca_rel" units="millimolar"/>
      <variable name="Ca_i" public_interface="in" units="millimolar"/>
      <variable initial_value="0.08" name="alpha_up" units="nanoA"/>
      <variable initial_value="0.072" name="beta_up" units="nanoA"/>
      <variable initial_value="0.5" name="alpha_rel" units="nanoA_per_millimolar"/>
      <variable name="K1" units="dimensionless"/>
      <variable name="K2" units="millimolar"/>
      <variable initial_value="0.00005" name="k_cyca" units="millimolar"/>
      <variable initial_value="0.9" name="k_xcs" units="dimensionless"/>
      <variable initial_value="22" name="k_SRCa" units="millimolar"/>
      <variable initial_value="0.004" name="k_rel" units="millimolar"/>
      <variable name="r_act" units="per_second"/>
      <variable name="r_inact" units="per_second"/>
      <variable initial_value="0.9528726" name="Ca_Calse" units="dimensionless"/>
      <variable name="phi_Calse" units="per_second"/>
      <variable initial_value="0.1133251" name="F1" units="dimensionless"/>
      <variable initial_value="0.0007594214" name="F2" units="dimensionless"/>
      <variable initial_value="0.8859153" name="F3" units="dimensionless"/>
      <variable name="V_i" public_interface="in" units="microLitre"/>
      <variable name="V_up" units="microLitre"/>
      <variable name="V_rel" units="microLitre"/>
      <variable name="F" public_interface="in" units="coulomb_per_mole"/>
      <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>V_up</ci>
            <apply>
               <times/>
               <cn xmlns:cellml="http://www.cellml.org/cellml/1.0#" cellml:units="dimensionless">0.01166</cn>
               <ci>V_i</ci>
            </apply>
         </apply>
         <apply>
            <eq/>
            <ci>V_rel</ci>
            <apply>
               <times/>
               <cn xmlns:cellml="http://www.cellml.org/cellml/1.0#" cellml:units="dimensionless">0.001296</cn>
               <ci>V_i</ci>
            </apply>
         </apply>
         <apply>
            <eq/>
            <ci>r_act</ci>
            <apply>
               <plus/>
               <apply>
                  <times/>
                  <cn xmlns:cellml="http://www.cellml.org/cellml/1.0#" cellml:units="per_second">240</cn>
                  <apply>
                     <exp/>
                     <apply>
                        <times/>
                        <apply>
                           <minus/>
                           <ci>V</ci>
                           <cn xmlns:cellml="http://www.cellml.org/cellml/1.0#" cellml:units="millivolt">40</cn>
                        </apply>
                        <cn xmlns:cellml="http://www.cellml.org/cellml/1.0#" cellml:units="per_millivolt">0.08</cn>
                     </apply>
                  </apply>
               </apply>
               <apply>
                  <times/>
                  <cn xmlns:cellml="http://www.cellml.org/cellml/1.0#" cellml:units="per_second">240</cn>
                  <apply>
                     <power/>
                     <apply>
                        <divide/>
                        <ci>Ca_i</ci>
                        <apply>
                           <plus/>
                           <ci>Ca_i</ci>
                           <ci>k_rel</ci>
                        </apply>
                     </apply>
                     <cn xmlns:cellml="http://www.cellml.org/cellml/1.0#" cellml:units="dimensionless">4</cn>
                  </apply>
               </apply>
            </apply>
         </apply>
         <apply>
            <eq/>
            <ci>r_inact</ci>
            <apply>
               <plus/>
               <cn xmlns:cellml="http://www.cellml.org/cellml/1.0#" cellml:units="per_second">40</cn>
               <apply>
                  <times/>
                  <cn xmlns:cellml="http://www.cellml.org/cellml/1.0#" cellml:units="per_second">240</cn>
                  <apply>
                     <power/>
                     <apply>
                        <divide/>
                        <ci>Ca_i</ci>
                        <apply>
                           <plus/>
                           <ci>Ca_i</ci>
                           <ci>k_rel</ci>
                        </apply>
                     </apply>
                     <cn xmlns:cellml="http://www.cellml.org/cellml/1.0#" cellml:units="dimensionless">4</cn>
                  </apply>
               </apply>
            </apply>
         </apply>
         <apply>
            <eq/>
            <ci>phi_Calse</ci>
            <apply>
               <minus/>
               <apply>
                  <times/>
                  <cn xmlns:cellml="http://www.cellml.org/cellml/1.0#" cellml:units="per_millimolar_second">770</cn>
                  <ci>Ca_rel</ci>
                  <apply>
                     <minus/>
                     <cn xmlns:cellml="http://www.cellml.org/cellml/1.0#" cellml:units="dimensionless">1</cn>
                     <ci>Ca_Calse</ci>
                  </apply>
               </apply>
               <apply>
                  <times/>
                  <cn xmlns:cellml="http://www.cellml.org/cellml/1.0#" cellml:units="per_second">641</cn>
                  <ci>Ca_Calse</ci>
               </apply>
            </apply>
         </apply>
         <apply>
            <eq/>
            <apply>
               <diff/>
               <bvar>
                  <ci>time</ci>
               </bvar>
               <ci>Ca_Calse</ci>
            </apply>
            <ci>phi_Calse</ci>
         </apply>
         <apply>
            <eq/>
            <apply>
               <diff/>
               <bvar>
                  <ci>time</ci>
               </bvar>
               <ci>F1</ci>
            </apply>
            <apply>
               <minus/>
               <apply>
                  <times/>
                  <cn xmlns:cellml="http://www.cellml.org/cellml/1.0#" cellml:units="per_second">0.96</cn>
                  <ci>F3</ci>
               </apply>
               <apply>
                  <times/>
                  <ci>r_act</ci>
                  <ci>F1</ci>
               </apply>
            </apply>
         </apply>
         <apply>
            <eq/>
            <apply>
               <diff/>
               <bvar>
                  <ci>time</ci>
               </bvar>
               <ci>F2</ci>
            </apply>
            <apply>
               <minus/>
               <apply>
                  <times/>
                  <ci>r_act</ci>
                  <ci>F1</ci>
               </apply>
               <apply>
                  <times/>
                  <ci>r_inact</ci>
                  <ci>F2</ci>
               </apply>
            </apply>
         </apply>
         <apply>
            <eq/>
            <apply>
               <diff/>
               <bvar>
                  <ci>time</ci>
               </bvar>
               <ci>F3</ci>
            </apply>
            <apply>
               <minus/>
               <apply>
                  <times/>
                  <ci>r_inact</ci>
                  <ci>F2</ci>
               </apply>
               <apply>
                  <times/>
                  <cn xmlns:cellml="http://www.cellml.org/cellml/1.0#" cellml:units="per_second">0.96</cn>
                  <ci>F3</ci>
               </apply>
            </apply>
         </apply>
         <apply>
            <eq/>
            <ci>K1</ci>
            <apply>
               <divide/>
               <apply>
                  <times/>
                  <ci>k_cyca</ci>
                  <ci>k_xcs</ci>
               </apply>
               <ci>k_SRCa</ci>
            </apply>
         </apply>
         <apply>
            <eq/>
            <ci>K2</ci>
            <apply>
               <plus/>
               <ci>Ca_i</ci>
               <apply>
                  <times/>
                  <ci>Ca_up</ci>
                  <ci>K1</ci>
               </apply>
               <apply>
                  <times/>
                  <ci>k_cyca</ci>
                  <ci>k_xcs</ci>
               </apply>
               <ci>k_cyca</ci>
            </apply>
         </apply>
         <apply>
            <eq/>
            <ci>i_up</ci>
            <apply>
               <divide/>
               <apply>
                  <minus/>
                  <apply>
                     <times/>
                     <ci>alpha_up</ci>
                     <ci>Ca_i</ci>
                  </apply>
                  <apply>
                     <times/>
                     <ci>beta_up</ci>
                     <ci>Ca_up</ci>
                     <ci>K1</ci>
                  </apply>
               </apply>
               <ci>K2</ci>
            </apply>
         </apply>
         <apply>
            <eq/>
            <ci>i_rel</ci>
            <apply>
               <times/>
               <ci>alpha_rel</ci>
               <apply>
                  <power/>
                  <apply>
                     <divide/>
                     <ci>F2</ci>
                     <apply>
                        <plus/>
                        <ci>F2</ci>
                        <cn xmlns:cellml="http://www.cellml.org/cellml/1.0#" cellml:units="dimensionless">0.25</cn>
                     </apply>
                  </apply>
                  <cn xmlns:cellml="http://www.cellml.org/cellml/1.0#" cellml:units="dimensionless">2</cn>
               </apply>
               <ci>Ca_rel</ci>
            </apply>
         </apply>
         <apply>
            <eq/>
            <ci>i_tr</ci>
            <apply>
               <divide/>
               <apply>
                  <times/>
                  <apply>
                     <minus/>
                     <ci>Ca_up</ci>
                     <ci>Ca_rel</ci>
                  </apply>
                  <cn xmlns:cellml="http://www.cellml.org/cellml/1.0#" cellml:units="dimensionless">2</cn>
                  <ci>F</ci>
                  <ci>V_up</ci>
               </apply>
               <cn xmlns:cellml="http://www.cellml.org/cellml/1.0#" cellml:units="second">0.06418</cn>
            </apply>
         </apply>
         <apply>
            <eq/>
            <apply>
               <diff/>
               <bvar>
                  <ci>time</ci>
               </bvar>
               <ci>Ca_up</ci>
            </apply>
            <apply>
               <divide/>
               <apply>
                  <minus/>
                  <ci>i_up</ci>
                  <ci>i_tr</ci>
               </apply>
               <apply>
                  <times/>
                  <cn xmlns:cellml="http://www.cellml.org/cellml/1.0#" cellml:units="dimensionless">2</cn>
                  <ci>V_up</ci>
                  <ci>F</ci>
               </apply>
            </apply>
         </apply>
         <apply>
            <eq/>
            <apply>
               <diff/>
               <bvar>
                  <ci>time</ci>
               </bvar>
               <ci>Ca_rel</ci>
            </apply>
            <apply>
               <minus/>
               <apply>
                  <divide/>
                  <apply>
                     <minus/>
                     <ci>i_tr</ci>
                     <ci>i_rel</ci>
                  </apply>
                  <apply>
                     <times/>
                     <cn xmlns:cellml="http://www.cellml.org/cellml/1.0#" cellml:units="dimensionless">2</cn>
                     <ci>V_rel</ci>
                     <ci>F</ci>
                  </apply>
               </apply>
               <apply>
                  <times/>
                  <cn xmlns:cellml="http://www.cellml.org/cellml/1.0#" cellml:units="millimolar">11.48</cn>
                  <ci>phi_Calse</ci>
               </apply>
            </apply>
         </apply>
      </math>
   </component>
   <component name="reversal_potentials">
      <variable name="E_Na" public_interface="out" units="millivolt"/>
      <variable name="E_K" public_interface="out" units="millivolt"/>
      <variable name="E_Ca" public_interface="out" units="millivolt"/>
      <variable name="K_c" public_interface="in" units="millimolar"/>
      <variable name="Na_c" public_interface="in" units="millimolar"/>
      <variable name="K_i" public_interface="in" units="millimolar"/>
      <variable name="Na_i" public_interface="in" units="millimolar"/>
      <variable name="Ca_c" public_interface="in" units="millimolar"/>
      <variable name="Ca_i" public_interface="in" units="millimolar"/>
      <variable name="R" public_interface="in" units="joule_per_kilomole_kelvin"/>
      <variable name="T" public_interface="in" units="kelvin"/>
      <variable name="F" public_interface="in" units="coulomb_per_mole"/>
      <variable name="time" public_interface="in" units="second"/>
      <math xmlns="http://www.w3.org/1998/Math/MathML">
         <apply>
            <eq/>
            <ci>E_Na</ci>
            <apply>
               <times/>
               <apply>
                  <divide/>
                  <apply>
                     <times/>
                     <ci>R</ci>
                     <ci>T</ci>
                  </apply>
                  <ci>F</ci>
               </apply>
               <apply>
                  <ln/>
                  <apply>
                     <divide/>
                     <ci>Na_c</ci>
                     <ci>Na_i</ci>
                  </apply>
               </apply>
            </apply>
         </apply>
         <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_c</ci>
                     <ci>K_i</ci>
                  </apply>
               </apply>
            </apply>
         </apply>
         <apply>
            <eq/>
            <ci>E_Ca</ci>
            <apply>
               <times/>
               <apply>
                  <divide/>
                  <apply>
                     <times/>
                     <cn xmlns:cellml="http://www.cellml.org/cellml/1.0#" cellml:units="dimensionless">0.5</cn>
                     <ci>R</ci>
                     <ci>T</ci>
                  </apply>
                  <ci>F</ci>
               </apply>
               <apply>
                  <ln/>
                  <apply>
                     <divide/>
                     <ci>Ca_c</ci>
                     <ci>Ca_i</ci>
                  </apply>
               </apply>
            </apply>
         </apply>
      </math>
   </component>
   <group>
      <relationship_ref relationship="containment"/>
      <component_ref component="membrane">
         <component_ref component="sodium_current">
            <component_ref component="sodium_current_m_gate"/>
            <component_ref component="sodium_current_h_gate"/>
         </component_ref>
         <component_ref component="L_type_Ca_channel">
            <component_ref component="L_type_Ca_channel_d_gate"/>
            <component_ref component="L_type_Ca_channel_f_gate"/>
         </component_ref>
         <component_ref component="T_type_Ca_channel">
            <component_ref component="T_type_Ca_channel_d_gate"/>
            <component_ref component="T_type_Ca_channel_f_gate"/>
         </component_ref>
         <component_ref component="delayed_rectifying_potassium_current">
            <component_ref component="delayed_rectifying_potassium_current_P_a_gate"/>
            <component_ref component="delayed_rectifying_potassium_current_P_i_gate"/>
         </component_ref>
         <component_ref component="linear_background_current"/>
         <component_ref component="hyperpolarisation_activated_current">
            <component_ref component="hyperpolarisation_activated_current_y_gate"/>
         </component_ref>
         <component_ref component="sodium_potassium_pump"/>
         <component_ref component="calcium_pump_current"/>
         <component_ref component="sodium_calcium_pump"/>
         <component_ref component="intracellular_concentrations_and_buffer_equations"/>
         <component_ref component="cleft_space_equations"/>
         <component_ref component="SR_Ca_uptake_and_release"/>
         <component_ref component="reversal_potentials"/>
      </component_ref>
   </group>
   <group>
      <relationship_ref relationship="encapsulation"/>
      <component_ref component="sodium_current">
         <component_ref component="sodium_current_m_gate"/>
         <component_ref component="sodium_current_h_gate"/>
      </component_ref>
      <component_ref component="L_type_Ca_channel">
         <component_ref component="L_type_Ca_channel_d_gate"/>
         <component_ref component="L_type_Ca_channel_f_gate"/>
      </component_ref>
      <component_ref component="T_type_Ca_channel">
         <component_ref component="T_type_Ca_channel_d_gate"/>
         <component_ref component="T_type_Ca_channel_f_gate"/>
      </component_ref>
      <component_ref component="delayed_rectifying_potassium_current">
         <component_ref component="delayed_rectifying_potassium_current_P_a_gate"/>
         <component_ref component="delayed_rectifying_potassium_current_P_i_gate"/>
      </component_ref>
      <component_ref component="hyperpolarisation_activated_current">
         <component_ref component="hyperpolarisation_activated_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>
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