Location: Hilgemann, Noble, 1987 @ cf54a3e5e327 / hilgemann_noble_1987.cellml

Author:
rcai987 <devnull@localhost>
Date:
2015-02-12 15:16:07+13:00
Desc:
Added annotations to hilgemann_noble_1987.cellml model
Permanent Source URI:
https://models.cellml.org/workspace/hilgemann_noble_1987/rawfile/cf54a3e5e327900d267b3b8bca0591702d1435c2/hilgemann_noble_1987.cellml

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This CellML file was generated on 19/09/2007 at 14:06:50 using:

COR (0.9.31.769)
Copyright 2002-2007 Dr Alan Garny
http://COR.physiol.ox.ac.uk/ - COR@physiol.ox.ac.uk

CellML 1.0 was used to generate this cellular model
http://www.CellML.org/
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<documentation xmlns="http://cellml.org/tmp-documentation">
<article>
  <articleinfo>
  <title>Hilemann-Noble Atrial Cell Model 1987</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 model is known to run in OpenCell and COR and reproduce the published results.
          </para>
  </section>
  <sect1 id="sec_structure">
<title>Model Structure</title>

<para>
ABSTRACT: Interactions of electrogenic sodium-calcium exchange, calcium channel and sarcoplasmic reticulum in the mammalian heart have been explored by simulation of extracellular calcium transients measured with tetramethylmurexide in rabbit atrium. The approach has been to use the simplest possible formulations of these mechanisms, which together with a minimum number of additional mechanisms allow reconstruction of action potentials, intracellular calcium transients and extracellular calcium transients. A 3:1 sodium-calcium exchange stoichiometry is assumed. Calcium-channel inactivation is assumed to take place by a voltage-dependent mechanism, which is accelerated by a rise in intracellular calcium; intracellular calcium release becomes a major physiological regulator of calcium influx via calcium channels. A calcium release mechanism is assumed, which is both calcium- and voltage-sensitive, and which undergoes prolonged inactivation. 200 microM cytosolic calcium buffer is assumed. For most simulations only instantaneous potassium conductances are simulated so as to study the other mechanisms independently of time- and calcium-dependent outward current. Thus, the model reconstructs extracellular calcium transients and typical action-potential configuration changes during steady-state and non-steady-state stimulation from the mechanisms directly involved in trans-sarcolemmal calcium movements. The model predicts relatively small trans-sarcolemmal calcium movements during regular stimulation (ca. 2 mumol kg-1 fresh mass per excitation); calcium current is fully activated within 2 ms of excitation, inactivation is substantially complete within 30 ms, and sodium-calcium exchange significantly resists repolarization from approximately -30 mV. Net calcium movements many times larger are possible during non-steady-state stimulation. Long action potentials at premature excitations or after inhibition of calcium release can be supported almost exclusively by calcium current (net calcium influx 5-30 mumol kg-1 fresh mass); action potentials during potentiated post-stimulatory contractions can be supported almost exclusively by sodium-calcium exchange (net calcium efflux 4-20 mumol kg-1 fresh mass). Large calcium movements between the extracellular space and the sarcoplasmic reticulum can take place through the cytosol with virtually no contractile activation. The simulations provide integrated explanations of electrical activity, contractile function and trans-sarcolemmal calcium movements, which were outside the explanatory range of previous models.
</para>

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

<para>
Excitation-contraction coupling and extracellular calcium transients in rabbit atrium: reconstruction of the basic cellular mechanisms, Hilemann, D.W. and Noble, D. 1987,<emphasis>Proc. R. Soc. Lond.</emphasis>, B230, 163-205. <ulink url="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&amp;db=PubMed&amp;list_uids=2884668&amp;dopt=Abstract">PubMed ID: 2884668</ulink>
</para>

<informalfigure float="0" id="fig_cell_diagram">
<mediaobject>
  <imageobject>
    <objectinfo>
      <title>cell diagram of the Hilemann-Noble model showing ionic currents across the sarcolemma</title>
    </objectinfo>
    <imagedata fileref="hilgemann_noble_1987.png"/>
  </imageobject>
</mediaobject>
<caption>A schematic diagram describing the current flows across the cell membrane that are captured in the Hilemann-Noble model.</caption>
</informalfigure>


</sect1>
</article>
</documentation>
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            <ci>E_Ca</ci>
            <apply>
               <times/>
               <cn xmlns:cellml="http://www.cellml.org/cellml/1.0#" cellml:units="dimensionless">0.5</cn>
               <ci>RTONF</ci>
               <apply>
                  <ln/>
                  <apply>
                     <divide/>
                     <ci>Ca_o</ci>
                     <ci>Ca_i</ci>
                  </apply>
               </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>
      </math>
   </component>
   <component cmeta:id="id_00028" name="Na_Ca_exchanger">
      <variable cmeta:id="Na_Ca_exchanger_i_NaCa" name="i_NaCa" public_interface="out" units="nanoA"/>
      <variable cmeta:id="id_00029" initial_value="0.01" name="k_NaCa" units="nanoA"/>
      <variable cmeta:id="id_00030" initial_value="3" name="n_NaCa" units="dimensionless"/>
      <variable cmeta:id="id_00031" initial_value="0.0001" name="d_NaCa" units="dimensionless"/>
      <variable initial_value="0.5" name="gamma" units="dimensionless"/>
      <variable name="time" public_interface="in" units="second"/>
      <variable name="V" public_interface="in" units="millivolt"/>
      <variable name="RTONF" public_interface="in" units="millivolt"/>
      <variable name="Ca_o" public_interface="in" units="millimolar"/>
      <variable name="Ca_i" public_interface="in" units="millimolar"/>
      <variable name="Na_i" public_interface="in" units="millimolar"/>
      <variable name="Na_o" public_interface="in" units="millimolar"/>
      <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>
                           <exp/>
                           <apply>
                              <divide/>
                              <apply>
                                 <times/>
                                 <ci>gamma</ci>
                                 <apply>
                                    <minus/>
                                    <ci>n_NaCa</ci>
                                    <cn xmlns:cellml="http://www.cellml.org/cellml/1.0#" cellml:units="dimensionless">2</cn>
                                 </apply>
                                 <ci>V</ci>
                              </apply>
                              <ci>RTONF</ci>
                           </apply>
                        </apply>
                        <apply>
                           <power/>
                           <ci>Na_i</ci>
                           <ci>n_NaCa</ci>
                        </apply>
                        <ci>Ca_o</ci>
                     </apply>
                     <apply>
                        <times/>
                        <apply>
                           <exp/>
                           <apply>
                              <divide/>
                              <apply>
                                 <times/>
                                 <apply>
                                    <minus/>
                                    <ci>gamma</ci>
                                    <cn xmlns:cellml="http://www.cellml.org/cellml/1.0#" cellml:units="dimensionless">1</cn>
                                 </apply>
                                 <apply>
                                    <minus/>
                                    <ci>n_NaCa</ci>
                                    <cn xmlns:cellml="http://www.cellml.org/cellml/1.0#" cellml:units="dimensionless">2</cn>
                                 </apply>
                                 <ci>V</ci>
                              </apply>
                              <ci>RTONF</ci>
                           </apply>
                        </apply>
                        <apply>
                           <power/>
                           <ci>Na_o</ci>
                           <ci>n_NaCa</ci>
                        </apply>
                        <ci>Ca_i</ci>
                     </apply>
                  </apply>
               </apply>
               <apply>
                  <times/>
                  <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_o</ci>
                                 <ci>n_NaCa</ci>
                              </apply>
                           </apply>
                           <apply>
                              <times/>
                              <ci>Ca_o</ci>
                              <apply>
                                 <power/>
                                 <ci>Na_i</ci>
                                 <ci>n_NaCa</ci>
                              </apply>
                           </apply>
                        </apply>
                     </apply>
                  </apply>
                  <apply>
                     <plus/>
                     <cn xmlns:cellml="http://www.cellml.org/cellml/1.0#" cellml:units="dimensionless">1</cn>
                     <apply>
                        <divide/>
                        <ci>Ca_i</ci>
                        <cn xmlns:cellml="http://www.cellml.org/cellml/1.0#" cellml:units="millimolar">0.0069</cn>
                     </apply>
                  </apply>
               </apply>
            </apply>
         </apply>
      </math>
   </component>
   <component cmeta:id="id_00016" name="potassium_background_current">
      <variable cmeta:id="id_00017" name="E_K" public_interface="in" units="millivolt"/>
      <variable cmeta:id="id_00019" name="i_b_K" public_interface="out" units="nanoA"/>
      <variable cmeta:id="id_00018" initial_value="0.17" name="g_b_K" units="microS"/>
      <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_K</ci>
            <apply>
               <times/>
               <ci>g_b_K</ci>
               <apply>
                  <minus/>
                  <ci>V</ci>
                  <ci>E_K</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="nanoA"/>
      <variable name="E_K" public_interface="out" units="millivolt"/>
      <variable initial_value="1.7" name="g_K1" units="microS"/>
      <variable initial_value="10" name="K_m_K1" units="millimolar"/>
      <variable name="time" public_interface="in" units="second"/>
      <variable name="V" public_interface="in" units="millivolt"/>
      <variable name="RTONF" public_interface="in" units="millivolt"/>
      <variable name="K_c" public_interface="in" units="millimolar"/>
      <variable name="K_i" public_interface="in" units="millimolar"/>
      <math xmlns="http://www.w3.org/1998/Math/MathML">
         <apply>
            <eq/>
            <ci>E_K</ci>
            <apply>
               <times/>
               <ci>RTONF</ci>
               <apply>
                  <ln/>
                  <apply>
                     <divide/>
                     <ci>K_c</ci>
                     <ci>K_i</ci>
                  </apply>
               </apply>
            </apply>
         </apply>
         <apply>
            <eq/>
            <ci>i_K1</ci>
            <apply>
               <divide/>
               <apply>
                  <times/>
                  <apply>
                     <divide/>
                     <apply>
                        <times/>
                        <ci>g_K1</ci>
                        <ci>K_c</ci>
                     </apply>
                     <apply>
                        <plus/>
                        <ci>K_c</ci>
                        <ci>K_m_K1</ci>
                     </apply>
                  </apply>
                  <apply>
                     <minus/>
                     <ci>V</ci>
                     <ci>E_K</ci>
                  </apply>
               </apply>
               <apply>
                  <plus/>
                  <cn xmlns:cellml="http://www.cellml.org/cellml/1.0#" cellml:units="dimensionless">1</cn>
                  <apply>
                     <exp/>
                     <apply>
                        <divide/>
                        <apply>
                           <times/>
                           <apply>
                              <minus/>
                              <apply>
                                 <minus/>
                                 <ci>V</ci>
                                 <ci>E_K</ci>
                              </apply>
                              <cn xmlns:cellml="http://www.cellml.org/cellml/1.0#" cellml:units="millivolt">10</cn>
                           </apply>
                           <cn xmlns:cellml="http://www.cellml.org/cellml/1.0#" cellml:units="dimensionless">2</cn>
                        </apply>
                        <ci>RTONF</ci>
                     </apply>
                  </apply>
               </apply>
            </apply>
         </apply>
      </math>
   </component>
   <component cmeta:id="id_00032" name="second_inward_calcium_current">
      <variable cmeta:id="id_00033" name="i_si" public_interface="out" units="nanoA"/>
      <variable cmeta:id="id_00034" name="i_siCa" public_interface="out" units="nanoA"/>
      <variable name="i_siK" public_interface="out" units="nanoA"/>
      <variable name="i_siNa" public_interface="out" units="nanoA"/>
      <variable initial_value="5" name="P_si" units="nanoA_per_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="Ca_i" private_interface="out" public_interface="in" units="millimolar"/>
      <variable name="RTONF" public_interface="in" units="millivolt"/>
      <variable name="Na_i" public_interface="in" units="millimolar"/>
      <variable name="Na_o" public_interface="in" units="millimolar"/>
      <variable name="Ca_o" public_interface="in" units="millimolar"/>
      <variable name="K_i" public_interface="in" units="millimolar"/>
      <variable name="K_c" public_interface="in" units="millimolar"/>
      <variable name="d" private_interface="in" units="dimensionless"/>
      <variable name="f_Ca" private_interface="in" units="dimensionless"/>
      <variable name="CaChon" private_interface="in" units="dimensionless"/>
      <math xmlns="http://www.w3.org/1998/Math/MathML">
         <apply>
            <eq/>
            <ci>i_si</ci>
            <apply>
               <plus/>
               <ci>i_siCa</ci>
               <ci>i_siK</ci>
               <ci>i_siNa</ci>
            </apply>
         </apply>
         <apply>
            <eq/>
            <ci>i_siCa</ci>
            <apply>
               <times/>
               <apply>
                  <divide/>
                  <apply>
                     <divide/>
                     <apply>
                        <times/>
                        <cn xmlns:cellml="http://www.cellml.org/cellml/1.0#" cellml:units="dimensionless">4</cn>
                        <ci>P_si</ci>
                        <ci>d</ci>
                        <ci>CaChon</ci>
                        <apply>
                           <minus/>
                           <ci>V</ci>
                           <cn xmlns:cellml="http://www.cellml.org/cellml/1.0#" cellml:units="millivolt">50</cn>
                        </apply>
                     </apply>
                     <ci>RTONF</ci>
                  </apply>
                  <apply>
                     <minus/>
                     <cn xmlns:cellml="http://www.cellml.org/cellml/1.0#" cellml:units="dimensionless">1</cn>
                     <apply>
                        <exp/>
                        <apply>
                           <divide/>
                           <apply>
                              <times/>
                              <apply>
                                 <minus/>
                                 <cn xmlns:cellml="http://www.cellml.org/cellml/1.0#" cellml:units="dimensionless">1</cn>
                              </apply>
                              <apply>
                                 <minus/>
                                 <ci>V</ci>
                                 <cn xmlns:cellml="http://www.cellml.org/cellml/1.0#" cellml:units="millivolt">50</cn>
                              </apply>
                              <cn xmlns:cellml="http://www.cellml.org/cellml/1.0#" cellml:units="dimensionless">2</cn>
                           </apply>
                           <ci>RTONF</ci>
                        </apply>
                     </apply>
                  </apply>
               </apply>
               <apply>
                  <minus/>
                  <apply>
                     <times/>
                     <ci>Ca_i</ci>
                     <apply>
                        <exp/>
                        <apply>
                           <divide/>
                           <cn xmlns:cellml="http://www.cellml.org/cellml/1.0#" cellml:units="millivolt">100</cn>
                           <ci>RTONF</ci>
                        </apply>
                     </apply>
                  </apply>
                  <apply>
                     <times/>
                     <ci>Ca_o</ci>
                     <apply>
                        <exp/>
                        <apply>
                           <divide/>
                           <apply>
                              <times/>
                              <apply>
                                 <minus/>
                                 <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">50</cn>
                              </apply>
                           </apply>
                           <ci>RTONF</ci>
                        </apply>
                     </apply>
                  </apply>
               </apply>
            </apply>
         </apply>
         <apply>
            <eq/>
            <ci>i_siK</ci>
            <apply>
               <times/>
               <apply>
                  <divide/>
                  <apply>
                     <divide/>
                     <apply>
                        <times/>
                        <cn xmlns:cellml="http://www.cellml.org/cellml/1.0#" cellml:units="dimensionless">0.002</cn>
                        <ci>P_si</ci>
                        <ci>d</ci>
                        <ci>CaChon</ci>
                        <apply>
                           <minus/>
                           <ci>V</ci>
                           <cn xmlns:cellml="http://www.cellml.org/cellml/1.0#" cellml:units="millivolt">50</cn>
                        </apply>
                     </apply>
                     <ci>RTONF</ci>
                  </apply>
                  <apply>
                     <minus/>
                     <cn xmlns:cellml="http://www.cellml.org/cellml/1.0#" cellml:units="dimensionless">1</cn>
                     <apply>
                        <exp/>
                        <apply>
                           <divide/>
                           <apply>
                              <times/>
                              <apply>
                                 <minus/>
                                 <cn xmlns:cellml="http://www.cellml.org/cellml/1.0#" cellml:units="dimensionless">1</cn>
                              </apply>
                              <apply>
                                 <minus/>
                                 <ci>V</ci>
                                 <cn xmlns:cellml="http://www.cellml.org/cellml/1.0#" cellml:units="millivolt">50</cn>
                              </apply>
                           </apply>
                           <ci>RTONF</ci>
                        </apply>
                     </apply>
                  </apply>
               </apply>
               <apply>
                  <minus/>
                  <apply>
                     <times/>
                     <ci>K_i</ci>
                     <apply>
                        <exp/>
                        <apply>
                           <divide/>
                           <cn xmlns:cellml="http://www.cellml.org/cellml/1.0#" cellml:units="millivolt">50</cn>
                           <ci>RTONF</ci>
                        </apply>
                     </apply>
                  </apply>
                  <apply>
                     <times/>
                     <ci>K_c</ci>
                     <apply>
                        <exp/>
                        <apply>
                           <divide/>
                           <apply>
                              <times/>
                              <apply>
                                 <minus/>
                                 <cn xmlns:cellml="http://www.cellml.org/cellml/1.0#" cellml:units="dimensionless">1</cn>
                              </apply>
                              <apply>
                                 <minus/>
                                 <ci>V</ci>
                                 <cn xmlns:cellml="http://www.cellml.org/cellml/1.0#" cellml:units="millivolt">50</cn>
                              </apply>
                           </apply>
                           <ci>RTONF</ci>
                        </apply>
                     </apply>
                  </apply>
               </apply>
            </apply>
         </apply>
         <apply>
            <eq/>
            <ci>i_siNa</ci>
            <apply>
               <times/>
               <apply>
                  <divide/>
                  <apply>
                     <divide/>
                     <apply>
                        <times/>
                        <cn xmlns:cellml="http://www.cellml.org/cellml/1.0#" cellml:units="dimensionless">0.01</cn>
                        <ci>P_si</ci>
                        <ci>d</ci>
                        <ci>CaChon</ci>
                        <apply>
                           <minus/>
                           <ci>V</ci>
                           <cn xmlns:cellml="http://www.cellml.org/cellml/1.0#" cellml:units="millivolt">50</cn>
                        </apply>
                     </apply>
                     <ci>RTONF</ci>
                  </apply>
                  <apply>
                     <minus/>
                     <cn xmlns:cellml="http://www.cellml.org/cellml/1.0#" cellml:units="dimensionless">1</cn>
                     <apply>
                        <exp/>
                        <apply>
                           <divide/>
                           <apply>
                              <times/>
                              <apply>
                                 <minus/>
                                 <cn xmlns:cellml="http://www.cellml.org/cellml/1.0#" cellml:units="dimensionless">1</cn>
                              </apply>
                              <apply>
                                 <minus/>
                                 <ci>V</ci>
                                 <cn xmlns:cellml="http://www.cellml.org/cellml/1.0#" cellml:units="millivolt">50</cn>
                              </apply>
                           </apply>
                           <ci>RTONF</ci>
                        </apply>
                     </apply>
                  </apply>
               </apply>
               <apply>
                  <minus/>
                  <apply>
                     <times/>
                     <ci>Na_i</ci>
                     <apply>
                        <exp/>
                        <apply>
                           <divide/>
                           <cn xmlns:cellml="http://www.cellml.org/cellml/1.0#" cellml:units="millivolt">50</cn>
                           <ci>RTONF</ci>
                        </apply>
                     </apply>
                  </apply>
                  <apply>
                     <times/>
                     <ci>Na_o</ci>
                     <apply>
                        <exp/>
                        <apply>
                           <divide/>
                           <apply>
                              <times/>
                              <apply>
                                 <minus/>
                                 <cn xmlns:cellml="http://www.cellml.org/cellml/1.0#" cellml:units="dimensionless">1</cn>
                              </apply>
                              <apply>
                                 <minus/>
                                 <ci>V</ci>
                                 <cn xmlns:cellml="http://www.cellml.org/cellml/1.0#" cellml:units="millivolt">50</cn>
                              </apply>
                           </apply>
                           <ci>RTONF</ci>
                        </apply>
                     </apply>
                  </apply>
               </apply>
            </apply>
         </apply>
      </math>
   </component>
   <component cmeta:id="id_00035" name="second_inward_calcium_current_d_gate">
      <variable initial_value="0.0011" name="d" public_interface="out" units="dimensionless"/>
      <variable name="alpha_d" units="per_second"/>
      <variable name="beta_d" units="per_second"/>
      <variable name="V" public_interface="in" units="millivolt"/>
      <variable name="time" public_interface="in" units="second"/>
      <variable initial_value="0.0001" name="delta_d" units="millivolt"/>
      <variable name="E0_d" units="millivolt"/>
      <math xmlns="http://www.w3.org/1998/Math/MathML">
         <apply>
            <eq/>
            <ci>E0_d</ci>
            <apply>
               <minus/>
               <apply>
                  <plus/>
                  <ci>V</ci>
                  <cn xmlns:cellml="http://www.cellml.org/cellml/1.0#" cellml:units="millivolt">24</cn>
               </apply>
               <cn xmlns:cellml="http://www.cellml.org/cellml/1.0#" cellml:units="millivolt">5</cn>
            </apply>
         </apply>
         <apply>
            <eq/>
            <ci>alpha_d</ci>
            <piecewise>
               <piece>
                  <cn xmlns:cellml="http://www.cellml.org/cellml/1.0#" cellml:units="per_second">120</cn>
                  <apply>
                     <lt/>
                     <apply>
                        <abs/>
                        <ci>E0_d</ci>
                     </apply>
                     <ci>delta_d</ci>
                  </apply>
               </piece>
               <otherwise>
                  <apply>
                     <divide/>
                     <apply>
                        <times/>
                        <cn xmlns:cellml="http://www.cellml.org/cellml/1.0#" cellml:units="per_millivolt_second">30</cn>
                        <ci>E0_d</ci>
                     </apply>
                     <apply>
                        <minus/>
                        <cn xmlns:cellml="http://www.cellml.org/cellml/1.0#" cellml:units="dimensionless">1</cn>
                        <apply>
                           <exp/>
                           <apply>
                              <divide/>
                              <apply>
                                 <times/>
                                 <apply>
                                    <minus/>
                                    <cn xmlns:cellml="http://www.cellml.org/cellml/1.0#" cellml:units="dimensionless">1</cn>
                                 </apply>
                                 <ci>E0_d</ci>
                              </apply>
                              <cn xmlns:cellml="http://www.cellml.org/cellml/1.0#" cellml:units="millivolt">4</cn>
                           </apply>
                        </apply>
                     </apply>
                  </apply>
               </otherwise>
            </piecewise>
         </apply>
         <apply>
            <eq/>
            <ci>beta_d</ci>
            <piecewise>
               <piece>
                  <cn xmlns:cellml="http://www.cellml.org/cellml/1.0#" cellml:units="per_second">120</cn>
                  <apply>
                     <lt/>
                     <apply>
                        <abs/>
                        <ci>E0_d</ci>
                     </apply>
                     <ci>delta_d</ci>
                  </apply>
               </piece>
               <otherwise>
                  <apply>
                     <divide/>
                     <apply>
                        <times/>
                        <cn xmlns:cellml="http://www.cellml.org/cellml/1.0#" cellml:units="per_millivolt_second">12</cn>
                        <ci>E0_d</ci>
                     </apply>
                     <apply>
                        <minus/>
                        <apply>
                           <exp/>
                           <apply>
                              <divide/>
                              <ci>E0_d</ci>
                              <cn xmlns:cellml="http://www.cellml.org/cellml/1.0#" cellml:units="millivolt">10</cn>
                           </apply>
                        </apply>
                        <cn xmlns:cellml="http://www.cellml.org/cellml/1.0#" cellml:units="dimensionless">1</cn>
                     </apply>
                  </apply>
               </otherwise>
            </piecewise>
         </apply>
         <apply>
            <eq/>
            <apply>
               <diff/>
               <bvar>
                  <ci>time</ci>
               </bvar>
               <ci>d</ci>
            </apply>
            <apply>
               <minus/>
               <apply>
                  <times/>
                  <ci>alpha_d</ci>
                  <apply>
                     <minus/>
                     <cn xmlns:cellml="http://www.cellml.org/cellml/1.0#" cellml:units="dimensionless">1</cn>
                     <ci>d</ci>
                  </apply>
               </apply>
               <apply>
                  <times/>
                  <ci>beta_d</ci>
                  <ci>d</ci>
               </apply>
            </apply>
         </apply>
      </math>
   </component>
   <component cmeta:id="id_00036" name="second_inward_calcium_current_f_Ca_gate">
      <variable initial_value="0.785" name="f_Ca" public_interface="out" units="dimensionless"/>
      <variable name="alpha_f_Ca" units="per_second"/>
      <variable name="beta_f_Ca" units="per_second"/>
      <variable name="CaChoff" units="dimensionless"/>
      <variable name="CaChon" public_interface="out" units="dimensionless"/>
      <variable name="V" public_interface="in" units="millivolt"/>
      <variable name="time" public_interface="in" units="second"/>
      <variable name="Ca_i" public_interface="in" units="millimolar"/>
      <variable initial_value="0.0001" name="delta_f" units="millivolt"/>
      <variable name="E0_f" units="millivolt"/>
      <math xmlns="http://www.w3.org/1998/Math/MathML">
         <apply>
            <eq/>
            <ci>E0_f</ci>
            <apply>
               <plus/>
               <ci>V</ci>
               <cn xmlns:cellml="http://www.cellml.org/cellml/1.0#" cellml:units="millivolt">34</cn>
            </apply>
         </apply>
         <apply>
            <eq/>
            <ci>alpha_f_Ca</ci>
            <piecewise>
               <piece>
                  <cn xmlns:cellml="http://www.cellml.org/cellml/1.0#" cellml:units="per_second">25</cn>
                  <apply>
                     <lt/>
                     <apply>
                        <abs/>
                        <ci>E0_f</ci>
                     </apply>
                     <ci>delta_f</ci>
                  </apply>
               </piece>
               <otherwise>
                  <apply>
                     <divide/>
                     <apply>
                        <times/>
                        <cn xmlns:cellml="http://www.cellml.org/cellml/1.0#" cellml:units="per_millivolt_second">6.25</cn>
                        <ci>E0_f</ci>
                     </apply>
                     <apply>
                        <minus/>
                        <apply>
                           <exp/>
                           <apply>
                              <divide/>
                              <ci>E0_f</ci>
                              <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>
               </otherwise>
            </piecewise>
         </apply>
         <apply>
            <eq/>
            <ci>beta_f_Ca</ci>
            <apply>
               <divide/>
               <cn xmlns:cellml="http://www.cellml.org/cellml/1.0#" cellml:units="per_second">12</cn>
               <apply>
                  <plus/>
                  <cn xmlns:cellml="http://www.cellml.org/cellml/1.0#" cellml:units="dimensionless">1</cn>
                  <apply>
                     <exp/>
                     <apply>
                        <divide/>
                        <apply>
                           <minus/>
                           <ci>E0_f</ci>
                        </apply>
                        <cn xmlns:cellml="http://www.cellml.org/cellml/1.0#" cellml:units="millivolt">4</cn>
                     </apply>
                  </apply>
               </apply>
            </apply>
         </apply>
         <apply>
            <eq/>
            <apply>
               <diff/>
               <bvar>
                  <ci>time</ci>
               </bvar>
               <ci>f_Ca</ci>
            </apply>
            <apply>
               <minus/>
               <apply>
                  <times/>
                  <apply>
                     <plus/>
                     <apply>
                        <times/>
                        <cn xmlns:cellml="http://www.cellml.org/cellml/1.0#" cellml:units="dimensionless">120</cn>
                        <apply>
                           <minus/>
                           <cn xmlns:cellml="http://www.cellml.org/cellml/1.0#" cellml:units="dimensionless">1</cn>
                           <ci>f_Ca</ci>
                        </apply>
                        <ci>CaChoff</ci>
                     </apply>
                     <apply>
                        <times/>
                        <apply>
                           <minus/>
                           <cn xmlns:cellml="http://www.cellml.org/cellml/1.0#" cellml:units="dimensionless">1</cn>
                           <ci>f_Ca</ci>
                        </apply>
                        <apply>
                           <minus/>
                           <cn xmlns:cellml="http://www.cellml.org/cellml/1.0#" cellml:units="dimensionless">1</cn>
                           <ci>CaChoff</ci>
                        </apply>
                     </apply>
                  </apply>
                  <ci>beta_f_Ca</ci>
               </apply>
               <apply>
                  <times/>
                  <ci>alpha_f_Ca</ci>
                  <ci>f_Ca</ci>
               </apply>
            </apply>
         </apply>
         <apply>
            <eq/>
            <ci>CaChoff</ci>
            <apply>
               <divide/>
               <ci>Ca_i</ci>
               <apply>
                  <plus/>
                  <cn xmlns:cellml="http://www.cellml.org/cellml/1.0#" cellml:units="millimolar">0.001</cn>
                  <ci>Ca_i</ci>
               </apply>
            </apply>
         </apply>
         <apply>
            <eq/>
            <ci>CaChon</ci>
            <apply>
               <times/>
               <apply>
                  <minus/>
                  <cn xmlns:cellml="http://www.cellml.org/cellml/1.0#" cellml:units="dimensionless">1</cn>
                  <ci>f_Ca</ci>
               </apply>
               <apply>
                  <minus/>
                  <cn xmlns:cellml="http://www.cellml.org/cellml/1.0#" cellml:units="dimensionless">1</cn>
                  <ci>CaChoff</ci>
               </apply>
            </apply>
         </apply>
      </math>
   </component>
   <component cmeta:id="id_00038" name="sarcoplasmic_reticulum_calcium_pump">
      <variable cmeta:id="id_00039" name="i_up" public_interface="out" units="millimolar_per_second"/>
      <variable cmeta:id="id_00040" name="K_1" units="dimensionless"/>
      <variable cmeta:id="id_00041" name="K_2" units="millimolar"/>
      <variable cmeta:id="id_00042" initial_value="0.0003" name="K_cyca" units="millimolar"/>
      <variable cmeta:id="id_00043" initial_value="0.4" name="K_xcs" units="dimensionless"/>
      <variable cmeta:id="id_00044" initial_value="0.5" name="K_srca" units="millimolar"/>
      <variable initial_value="3" name="alpha_up" units="millimolar_per_second"/>
      <variable initial_value="0.23" name="beta_up" units="millimolar_per_second"/>
      <variable name="Ca_up" public_interface="in" units="millimolar"/>
      <variable name="time" public_interface="in" units="second"/>
      <variable name="Ca_i" public_interface="in" units="millimolar"/>
      <math xmlns="http://www.w3.org/1998/Math/MathML">
         <apply>
            <eq/>
            <ci>K_1</ci>
            <apply>
               <divide/>
               <apply>
                  <times/>
                  <ci>K_cyca</ci>
                  <ci>K_xcs</ci>
               </apply>
               <ci>K_srca</ci>
            </apply>
         </apply>
         <apply>
            <eq/>
            <ci>K_2</ci>
            <apply>
               <plus/>
               <ci>Ca_i</ci>
               <apply>
                  <times/>
                  <ci>Ca_up</ci>
                  <ci>K_1</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>
               <minus/>
               <apply>
                  <times/>
                  <apply>
                     <divide/>
                     <ci>Ca_i</ci>
                     <ci>K_2</ci>
                  </apply>
                  <ci>alpha_up</ci>
               </apply>
               <apply>
                  <times/>
                  <apply>
                     <divide/>
                     <apply>
                        <times/>
                        <ci>Ca_up</ci>
                        <ci>K_1</ci>
                     </apply>
                     <ci>K_2</ci>
                  </apply>
                  <ci>beta_up</ci>
               </apply>
            </apply>
         </apply>
      </math>
   </component>
   <component name="calcium_release">
      <variable cmeta:id="calcium_release_i_rel" name="i_rel" public_interface="out" units="millimolar_per_second"/>
      <variable name="VoltDep" units="dimensionless"/>
      <variable name="RegBindSite" units="dimensionless"/>
      <variable name="ActRate" units="per_second"/>
      <variable name="InactRate" units="per_second"/>
      <variable initial_value="0" name="K_leak_rate" units="per_second"/>
      <variable initial_value="250" name="K_m_rel" units="per_second"/>
      <variable name="PrecFrac" units="dimensionless"/>
      <variable initial_value="0" name="ActFrac" units="dimensionless"/>
      <variable initial_value="0" name="ProdFrac" units="dimensionless"/>
      <variable name="time" public_interface="in" units="second"/>
      <variable name="V" public_interface="in" units="millivolt"/>
      <variable name="Ca_i" public_interface="in" units="millimolar"/>
      <variable name="Ca_rel" public_interface="in" units="millimolar"/>
      <math xmlns="http://www.w3.org/1998/Math/MathML">
         <apply>
            <eq/>
            <ci>PrecFrac</ci>
            <apply>
               <minus/>
               <apply>
                  <minus/>
                  <cn xmlns:cellml="http://www.cellml.org/cellml/1.0#" cellml:units="dimensionless">1</cn>
                  <ci>ActFrac</ci>
               </apply>
               <ci>ProdFrac</ci>
            </apply>
         </apply>
         <apply>
            <eq/>
            <ci>VoltDep</ci>
            <apply>
               <exp/>
               <apply>
                  <times/>
                  <cn xmlns:cellml="http://www.cellml.org/cellml/1.0#" cellml:units="per_millivolt">0.08</cn>
                  <apply>
                     <minus/>
                     <ci>V</ci>
                     <cn xmlns:cellml="http://www.cellml.org/cellml/1.0#" cellml:units="millivolt">40</cn>
                  </apply>
               </apply>
            </apply>
         </apply>
         <apply>
            <eq/>
            <ci>RegBindSite</ci>
            <apply>
               <power/>
               <apply>
                  <divide/>
                  <ci>Ca_i</ci>
                  <apply>
                     <plus/>
                     <ci>Ca_i</ci>
                     <cn xmlns:cellml="http://www.cellml.org/cellml/1.0#" cellml:units="millimolar">0.0005</cn>
                  </apply>
               </apply>
               <cn xmlns:cellml="http://www.cellml.org/cellml/1.0#" cellml:units="dimensionless">2</cn>
            </apply>
         </apply>
         <apply>
            <eq/>
            <ci>ActRate</ci>
            <apply>
               <plus/>
               <apply>
                  <times/>
                  <cn xmlns:cellml="http://www.cellml.org/cellml/1.0#" cellml:units="per_second">600</cn>
                  <ci>VoltDep</ci>
               </apply>
               <apply>
                  <times/>
                  <cn xmlns:cellml="http://www.cellml.org/cellml/1.0#" cellml:units="per_second">500</cn>
                  <ci>RegBindSite</ci>
               </apply>
            </apply>
         </apply>
         <apply>
            <eq/>
            <ci>InactRate</ci>
            <apply>
               <plus/>
               <cn xmlns:cellml="http://www.cellml.org/cellml/1.0#" cellml:units="per_second">60</cn>
               <apply>
                  <times/>
                  <cn xmlns:cellml="http://www.cellml.org/cellml/1.0#" cellml:units="per_second">500</cn>
                  <ci>RegBindSite</ci>
               </apply>
            </apply>
         </apply>
         <apply>
            <eq/>
            <apply>
               <diff/>
               <bvar>
                  <ci>time</ci>
               </bvar>
               <ci>ActFrac</ci>
            </apply>
            <apply>
               <minus/>
               <apply>
                  <times/>
                  <ci>PrecFrac</ci>
                  <ci>ActRate</ci>
               </apply>
               <apply>
                  <times/>
                  <ci>ActFrac</ci>
                  <ci>InactRate</ci>
               </apply>
            </apply>
         </apply>
         <apply>
            <eq/>
            <apply>
               <diff/>
               <bvar>
                  <ci>time</ci>
               </bvar>
               <ci>ProdFrac</ci>
            </apply>
            <apply>
               <minus/>
               <apply>
                  <times/>
                  <ci>ActFrac</ci>
                  <ci>InactRate</ci>
               </apply>
               <apply>
                  <times/>
                  <cn xmlns:cellml="http://www.cellml.org/cellml/1.0#" cellml:units="per_second">0.6</cn>
                  <ci>ProdFrac</ci>
               </apply>
            </apply>
         </apply>
         <apply>
            <eq/>
            <ci>i_rel</ci>
            <apply>
               <times/>
               <apply>
                  <plus/>
                  <apply>
                     <times/>
                     <apply>
                        <power/>
                        <apply>
                           <divide/>
                           <ci>ActFrac</ci>
                           <apply>
                              <plus/>
                              <ci>ActFrac</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>K_m_rel</ci>
                  </apply>
                  <ci>K_leak_rate</ci>
               </apply>
               <ci>Ca_rel</ci>
            </apply>
         </apply>
      </math>
   </component>
   <component name="calcium_translocation">
      <variable cmeta:id="calcium_translocation_i_trans" name="i_trans" public_interface="out" units="millimolar_per_second"/>
      <variable name="Ca_rel" public_interface="in" units="millimolar"/>
      <variable name="Ca_up" public_interface="in" units="millimolar"/>
      <variable initial_value="50" name="alpha_tr" units="per_second"/>
      <variable name="time" public_interface="in" units="second"/>
      <math xmlns="http://www.w3.org/1998/Math/MathML">
         <apply>
            <eq/>
            <ci>i_trans</ci>
            <apply>
               <times/>
               <apply>
                  <minus/>
                  <ci>Ca_up</ci>
                  <ci>Ca_rel</ci>
               </apply>
               <ci>alpha_tr</ci>
            </apply>
         </apply>
      </math>
   </component>
   <component cmeta:id="id_00050" name="extracellular_sodium_concentration">
      <variable cmeta:id="id_00051" initial_value="140" name="Na_o" public_interface="out" units="millimolar"/>
   </component>
   <component cmeta:id="id_00052" name="intracellular_sodium_concentration">
      <variable cmeta:id="id_00053" initial_value="6.5" name="Na_i" public_interface="out" units="millimolar"/>
      <variable name="V_i" public_interface="in" units="micrometre3"/>
      <variable name="time" public_interface="in" units="second"/>
      <variable name="F" public_interface="in" units="coulomb_per_mole"/>
      <variable cmeta:id="id_00054" name="i_Na" public_interface="in" units="nanoA"/>
      <variable cmeta:id="id_00057" name="i_b_Na" public_interface="in" units="nanoA"/>
      <variable name="i_siNa" public_interface="in" units="nanoA"/>
      <variable cmeta:id="id_00055" name="i_NaK" public_interface="in" units="nanoA"/>
      <variable cmeta:id="id_00056" name="i_NaCa" public_interface="in" units="nanoA"/>
      <math xmlns="http://www.w3.org/1998/Math/MathML">
         <apply>
            <eq/>
            <apply>
               <diff/>
               <bvar>
                  <ci>time</ci>
               </bvar>
               <ci>Na_i</ci>
            </apply>
            <apply>
               <times/>
               <apply>
                  <divide/>
                  <apply>
                     <minus/>
                     <cn xmlns:cellml="http://www.cellml.org/cellml/1.0#" cellml:units="mA_nA">1</cn>
                  </apply>
                  <apply>
                     <times/>
                     <cn xmlns:cellml="http://www.cellml.org/cellml/1.0#" cellml:units="litre_micrometre3">1</cn>
                     <ci>V_i</ci>
                     <ci>F</ci>
                  </apply>
               </apply>
               <apply>
                  <plus/>
                  <ci>i_Na</ci>
                  <ci>i_b_Na</ci>
                  <apply>
                     <times/>
                     <ci>i_NaK</ci>
                     <cn xmlns:cellml="http://www.cellml.org/cellml/1.0#" cellml:units="dimensionless">3</cn>
                  </apply>
                  <apply>
                     <times/>
                     <ci>i_NaCa</ci>
                     <cn xmlns:cellml="http://www.cellml.org/cellml/1.0#" cellml:units="dimensionless">3</cn>
                  </apply>
                  <ci>i_siNa</ci>
               </apply>
            </apply>
         </apply>
      </math>
   </component>
   <component cmeta:id="id_00048" name="extracellular_calcium_concentration">
      <variable cmeta:id="id_00049" initial_value="2" name="Ca_o" public_interface="out" units="millimolar"/>
      <variable name="i_NaCa" public_interface="in" units="nanoA"/>
      <variable initial_value="2" name="Cab" units="millimolar"/>
      <variable initial_value="0.0005" name="K_diff" units="per_second"/>
      <variable name="Ve" public_interface="in" units="micrometre3"/>
      <variable name="F" public_interface="in" units="coulomb_per_mole"/>
      <variable name="time" public_interface="in" units="second"/>
      <variable cmeta:id="id_00058" name="i_siCa" public_interface="in" units="nanoA"/>
      <variable cmeta:id="id_00059" name="i_b_Ca" public_interface="in" units="nanoA"/>
      <math xmlns="http://www.w3.org/1998/Math/MathML">
         <apply>
            <eq/>
            <apply>
               <diff/>
               <bvar>
                  <ci>time</ci>
               </bvar>
               <ci>Ca_o</ci>
            </apply>
            <apply>
               <minus/>
               <apply>
                  <times/>
                  <apply>
                     <minus/>
                     <ci>Cab</ci>
                     <ci>Ca_o</ci>
                  </apply>
                  <ci>K_diff</ci>
               </apply>
               <apply>
                  <divide/>
                  <apply>
                     <times/>
                     <cn xmlns:cellml="http://www.cellml.org/cellml/1.0#" cellml:units="mA_nA">1</cn>
                     <apply>
                        <plus/>
                        <ci>i_siCa</ci>
                        <ci>i_NaCa</ci>
                        <ci>i_b_Ca</ci>
                     </apply>
                  </apply>
                  <apply>
                     <times/>
                     <cn xmlns:cellml="http://www.cellml.org/cellml/1.0#" cellml:units="dimensionless">2</cn>
                     <cn xmlns:cellml="http://www.cellml.org/cellml/1.0#" cellml:units="litre_micrometre3">1</cn>
                     <ci>Ve</ci>
                     <ci>F</ci>
                  </apply>
               </apply>
            </apply>
         </apply>
      </math>
   </component>
   <component cmeta:id="id_00047" name="extracellular_potassium_concentration">
      <variable initial_value="4" name="K_c" public_interface="out" units="millimolar"/>
   </component>
   <component cmeta:id="id_00046" name="intracellular_potassium_concentration">
      <variable initial_value="140" name="K_i" public_interface="out" units="millimolar"/>
      <variable name="V_i" public_interface="in" units="micrometre3"/>
      <variable name="i_K1" public_interface="in" units="nanoA"/>
      <variable name="i_siK" public_interface="in" units="nanoA"/>
      <variable name="i_b_K" public_interface="in" units="nanoA"/>
      <variable name="i_NaK" public_interface="in" units="nanoA"/>
      <variable name="time" public_interface="in" units="second"/>
      <variable name="F" public_interface="in" units="coulomb_per_mole"/>
      <math xmlns="http://www.w3.org/1998/Math/MathML">
         <apply>
            <eq/>
            <apply>
               <diff/>
               <bvar>
                  <ci>time</ci>
               </bvar>
               <ci>K_i</ci>
            </apply>
            <apply>
               <times/>
               <apply>
                  <divide/>
                  <apply>
                     <minus/>
                     <cn xmlns:cellml="http://www.cellml.org/cellml/1.0#" cellml:units="mA_nA">1</cn>
                  </apply>
                  <apply>
                     <times/>
                     <cn xmlns:cellml="http://www.cellml.org/cellml/1.0#" cellml:units="litre_micrometre3">1</cn>
                     <ci>V_i</ci>
                     <ci>F</ci>
                  </apply>
               </apply>
               <apply>
                  <minus/>
                  <apply>
                     <plus/>
                     <ci>i_K1</ci>
                     <ci>i_siK</ci>
                     <ci>i_b_K</ci>
                  </apply>
                  <apply>
                     <times/>
                     <cn xmlns:cellml="http://www.cellml.org/cellml/1.0#" cellml:units="dimensionless">2</cn>
                     <ci>i_NaK</ci>
                  </apply>
               </apply>
            </apply>
         </apply>
      </math>
   </component>
   <component cmeta:id="id_00045" name="intracellular_calcium_concentration">
      <variable cmeta:id="intracellular_calcium_concentration_Ca_i" initial_value="1e-5" name="Ca_i" public_interface="out" units="millimolar"/>
      <variable initial_value="0.3" name="Ca_up" public_interface="out" units="millimolar"/>
      <variable initial_value="0.3" name="Ca_rel" public_interface="out" units="millimolar"/>
      <variable cmeta:id="id_00063" initial_value="0.0005" name="Ca_Calmod" units="millimolar"/>
      <variable cmeta:id="id_00068" initial_value="0.0015" name="Ca_Trop" units="millimolar"/>
      <variable cmeta:id="id_00064" initial_value="0.02" name="Calmod" units="millimolar"/>
      <variable cmeta:id="id_00069" initial_value="0.15" name="Trop" units="millimolar"/>
      <variable cmeta:id="id_00065" initial_value="100000" name="alpha_Calmod" units="per_millimolar_second"/>
      <variable cmeta:id="id_00066" initial_value="50" name="beta_Calmod" units="per_second"/>
      <variable cmeta:id="id_00070" initial_value="100000" name="alpha_Trop" units="per_millimolar_second"/>
      <variable cmeta:id="id_00071" initial_value="200" name="beta_Trop" units="per_second"/>
      <variable initial_value="0.08" name="radius" units="micrometre"/>
      <variable initial_value="0.08" name="length" units="micrometre"/>
      <variable name="V_i" public_interface="out" units="micrometre3"/>
      <variable name="Ve" public_interface="out" units="micrometre3"/>
      <variable name="V_Cell" units="micrometre3"/>
      <variable name="V_i_ratio" units="dimensionless"/>
      <variable initial_value="0.1" name="V_rel_ratio" units="dimensionless"/>
      <variable initial_value="0.4" name="V_e_ratio" units="dimensionless"/>
      <variable initial_value="0.01" name="V_up_ratio" units="dimensionless"/>
      <variable name="i_up" public_interface="in" units="millimolar_per_second"/>
      <variable name="i_trans" public_interface="in" units="millimolar_per_second"/>
      <variable name="i_rel" public_interface="in" units="millimolar_per_second"/>
      <variable cmeta:id="id_00062" name="i_NaCa" public_interface="in" units="nanoA"/>
      <variable cmeta:id="id_00060" name="i_siCa" public_interface="in" units="nanoA"/>
      <variable cmeta:id="id_00061" 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_Cell</ci>
            <apply>
               <times/>
               <cn xmlns:cellml="http://www.cellml.org/cellml/1.0#" cellml:units="dimensionless">3.141592654</cn>
               <apply>
                  <power/>
                  <ci>radius</ci>
                  <cn xmlns:cellml="http://www.cellml.org/cellml/1.0#" cellml:units="dimensionless">2</cn>
               </apply>
               <ci>length</ci>
            </apply>
         </apply>
         <apply>
            <eq/>
            <ci>V_i_ratio</ci>
            <apply>
               <minus/>
               <apply>
                  <minus/>
                  <apply>
                     <minus/>
                     <cn xmlns:cellml="http://www.cellml.org/cellml/1.0#" cellml:units="dimensionless">1</cn>
                     <ci>V_e_ratio</ci>
                  </apply>
                  <ci>V_up_ratio</ci>
               </apply>
               <ci>V_rel_ratio</ci>
            </apply>
         </apply>
         <apply>
            <eq/>
            <ci>V_i</ci>
            <apply>
               <times/>
               <ci>V_Cell</ci>
               <ci>V_i_ratio</ci>
            </apply>
         </apply>
         <apply>
            <eq/>
            <ci>Ve</ci>
            <apply>
               <times/>
               <ci>V_Cell</ci>
               <ci>V_e_ratio</ci>
            </apply>
         </apply>
         <apply>
        <eq/>
        <apply>
          <diff/>
          <bvar>
            <ci>time</ci>
          </bvar>
          <ci>Ca_i</ci>
        </apply>
        <apply>
          <minus/>
          <apply>
            <minus/>
            <apply>
              <minus/>
              <apply>
                <plus/>
                <apply>
                  <times/>
                  <apply>
                    <divide/>
                    <apply>
                      <minus/>
                      <cn xmlns:cellml="http://www.cellml.org/cellml/1.0#" cellml:units="mA_nA">1</cn>
                    </apply>
                    <apply>
                      <times/>
                      <cn xmlns:cellml="http://www.cellml.org/cellml/1.0#" cellml:units="dimensionless">2</cn>
                      <cn xmlns:cellml="http://www.cellml.org/cellml/1.0#" cellml:units="litre_micrometre3">1</cn>
                      <ci>V_i</ci>
                      <ci>F</ci>
                    </apply>
                  </apply>
                  <apply>
                    <minus/>
                    <apply>
                      <plus/>
                      <ci>i_siCa</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>i_NaCa</ci>
                    </apply>
                  </apply>
                </apply>
                <apply>
                  <divide/>
                  <apply>
                    <times/>
                    <ci>i_rel</ci>
                    <ci>V_rel_ratio</ci>
                  </apply>
                  <ci>V_i_ratio</ci>
                </apply>
              </apply>
              <ci>dCaCalmoddt</ci>
            </apply>
            <ci>dCaTropdt</ci>
          </apply>
          <ci>i_up</ci>
        </apply>
      </apply>
         <apply>
            <eq/>
            <apply>
               <diff/>
               <bvar>
                  <ci>time</ci>
               </bvar>
               <ci>Ca_up</ci>
            </apply>
            <apply>
               <minus/>
               <apply>
                  <times/>
                  <apply>
                     <divide/>
                     <ci>V_i_ratio</ci>
                     <ci>V_up_ratio</ci>
                  </apply>
                  <ci>i_up</ci>
               </apply>
               <ci>i_trans</ci>
            </apply>
         </apply>
         <apply>
            <eq/>
            <apply>
               <diff/>
               <bvar>
                  <ci>time</ci>
               </bvar>
               <ci>Ca_rel</ci>
            </apply>
            <apply>
               <minus/>
               <apply>
                  <times/>
                  <apply>
                     <divide/>
                     <ci>V_up_ratio</ci>
                     <ci>V_rel_ratio</ci>
                  </apply>
                  <ci>i_trans</ci>
               </apply>
               <ci>i_rel</ci>
            </apply>
         </apply>
         <apply>
            <eq/>
            <apply>
               <diff/>
               <bvar>
                  <ci>time</ci>
               </bvar>
               <ci>Ca_Calmod</ci>
            </apply>
            <apply>
               <minus/>
               <apply>
                  <times/>
                  <ci>alpha_Calmod</ci>
                  <ci>Ca_i</ci>
                  <apply>
                     <minus/>
                     <ci>Calmod</ci>
                     <ci>Ca_Calmod</ci>
                  </apply>
               </apply>
               <apply>
                  <times/>
                  <ci>beta_Calmod</ci>
                  <ci>Ca_Calmod</ci>
               </apply>
            </apply>
         </apply>
         <apply>
            <eq/>
            <apply>
               <diff/>
               <bvar>
                  <ci>time</ci>
               </bvar>
               <ci>Ca_Trop</ci>
            </apply>
            <apply>
               <minus/>
               <apply>
                  <times/>
                  <ci>alpha_Trop</ci>
                  <ci>Ca_i</ci>
                  <apply>
                     <minus/>
                     <ci>Trop</ci>
                     <ci>Ca_Trop</ci>
                  </apply>
               </apply>
               <apply>
                  <times/>
                  <ci>beta_Trop</ci>
                  <ci>Ca_Trop</ci>
               </apply>
            </apply>
         </apply>
      <apply>
        <eq/>
        <ci>dCaCalmoddt</ci>
        <apply>
          <minus/>
          <apply>
            <times/>
            <ci>alpha_Calmod</ci>
            <ci>Ca_i</ci>
            <apply>
              <minus/>
              <ci>Calmod</ci>
              <ci>Ca_Calmod</ci>
            </apply>
          </apply>
          <apply>
            <times/>
            <ci>beta_Calmod</ci>
            <ci>Ca_Calmod</ci>
          </apply>
        </apply>
      </apply>
      <apply>
        <eq/>
        <ci>dCaTropdt</ci>
        <apply>
          <minus/>
          <apply>
            <times/>
            <ci>alpha_Trop</ci>
            <ci>Ca_i</ci>
            <apply>
              <minus/>
              <ci>Trop</ci>
              <ci>Ca_Trop</ci>
            </apply>
          </apply>
          <apply>
            <times/>
            <ci>beta_Trop</ci>
            <ci>Ca_Trop</ci>
          </apply>
        </apply>
      </apply>
    </math>
   <variable cmeta:id="id_00067" name="dCaCalmoddt" units="millimolar_per_second"/>
    <variable cmeta:id="id_00072" name="dCaTropdt" units="millimolar_per_second"/>
  </component>
   <group>
      <relationship_ref relationship="containment"/>
      <component_ref component="membrane">
         <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_ref component="sodium_potassium_pump"/>
         <component_ref component="sodium_background_current"/>
         <component_ref component="calcium_background_current"/>
         <component_ref component="potassium_background_current"/>
         <component_ref component="Na_Ca_exchanger"/>
         <component_ref component="time_independent_potassium_current"/>
         <component_ref component="second_inward_calcium_current">
            <component_ref component="second_inward_calcium_current_d_gate"/>
            <component_ref component="second_inward_calcium_current_f_Ca_gate"/>
         </component_ref>
         <component_ref component="sarcoplasmic_reticulum_calcium_pump"/>
         <component_ref component="intracellular_calcium_concentration"/>
         <component_ref component="calcium_release"/>
         <component_ref component="calcium_translocation"/>
         <component_ref component="extracellular_calcium_concentration"/>
         <component_ref component="intracellular_sodium_concentration"/>
         <component_ref component="extracellular_sodium_concentration"/>
         <component_ref component="intracellular_potassium_concentration"/>
         <component_ref component="extracellular_potassium_concentration"/>
      </component_ref>
   </group>
   <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_ref component="second_inward_calcium_current">
         <component_ref component="second_inward_calcium_current_d_gate"/>
         <component_ref component="second_inward_calcium_current_f_Ca_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="sodium_potassium_pump" 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="calcium_background_current" component_2="environment"/>
      <map_variables variable_1="time" variable_2="time"/>
   </connection>
   <connection>
      <map_components component_1="potassium_background_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="time_independent_potassium_current" component_2="environment"/>
      <map_variables variable_1="time" variable_2="time"/>
   </connection>
   <connection>
      <map_components component_1="second_inward_calcium_current" component_2="environment"/>
      <map_variables variable_1="time" variable_2="time"/>
   </connection>
   <connection>
      <map_components component_1="sarcoplasmic_reticulum_calcium_pump" component_2="environment"/>
      <map_variables variable_1="time" variable_2="time"/>
   </connection>
   <connection>
      <map_components component_1="calcium_release" component_2="environment"/>
      <map_variables variable_1="time" variable_2="time"/>
   </connection>
   <connection>
      <map_components component_1="calcium_translocation" component_2="environment"/>
      <map_variables variable_1="time" variable_2="time"/>
   </connection>
   <connection>
      <map_components component_1="extracellular_calcium_concentration" component_2="environment"/>
      <map_variables variable_1="time" variable_2="time"/>
   </connection>
   <connection>
      <map_components component_1="intracellular_calcium_concentration" component_2="environment"/>
      <map_variables variable_1="time" variable_2="time"/>
   </connection>
   <connection>
      <map_components component_1="intracellular_sodium_concentration" component_2="environment"/>
      <map_variables variable_1="time" variable_2="time"/>
   </connection>
   <connection>
      <map_components component_1="intracellular_potassium_concentration" component_2="environment"/>
      <map_variables variable_1="time" variable_2="time"/>
   </connection>
   <connection>
      <map_components component_1="fast_sodium_current" component_2="membrane"/>
      <map_variables variable_1="i_Na" variable_2="i_Na"/>
      <map_variables variable_1="V" variable_2="V"/>
      <map_variables variable_1="RTONF" variable_2="RTONF"/>
   </connection>
   <connection>
      <map_components component_1="sodium_potassium_pump" component_2="membrane"/>
      <map_variables variable_1="i_NaK" variable_2="i_NaK"/>
      <map_variables variable_1="V" variable_2="V"/>
   </connection>
   <connection>
      <map_components component_1="sodium_background_current" component_2="membrane"/>
      <map_variables variable_1="i_b_Na" variable_2="i_b_Na"/>
      <map_variables variable_1="V" variable_2="V"/>
      <map_variables variable_1="RTONF" variable_2="RTONF"/>
   </connection>
   <connection>
      <map_components component_1="calcium_background_current" component_2="membrane"/>
      <map_variables variable_1="i_b_Ca" variable_2="i_b_Ca"/>
      <map_variables variable_1="V" variable_2="V"/>
      <map_variables variable_1="RTONF" variable_2="RTONF"/>
   </connection>
   <connection>
      <map_components component_1="potassium_background_current" component_2="membrane"/>
      <map_variables variable_1="i_b_K" variable_2="i_b_K"/>
      <map_variables variable_1="V" variable_2="V"/>
   </connection>
   <connection>
      <map_components component_1="Na_Ca_exchanger" component_2="membrane"/>
      <map_variables variable_1="V" variable_2="V"/>
      <map_variables variable_1="i_NaCa" variable_2="i_NaCa"/>
      <map_variables variable_1="RTONF" variable_2="RTONF"/>
   </connection>
   <connection>
      <map_components component_1="time_independent_potassium_current" component_2="membrane"/>
      <map_variables variable_1="i_K1" variable_2="i_K1"/>
      <map_variables variable_1="V" variable_2="V"/>
      <map_variables variable_1="RTONF" variable_2="RTONF"/>
   </connection>
   <connection>
      <map_components component_1="second_inward_calcium_current" component_2="membrane"/>
      <map_variables variable_1="i_si" variable_2="i_si"/>
      <map_variables variable_1="V" variable_2="V"/>
      <map_variables variable_1="RTONF" variable_2="RTONF"/>
   </connection>
   <connection>
      <map_components component_1="calcium_release" component_2="membrane"/>
      <map_variables variable_1="V" variable_2="V"/>
   </connection>
   <connection>
      <map_components component_1="intracellular_calcium_concentration" component_2="membrane"/>
      <map_variables variable_1="F" variable_2="F"/>
   </connection>
   <connection>
      <map_components component_1="intracellular_sodium_concentration" component_2="membrane"/>
      <map_variables variable_1="F" variable_2="F"/>
   </connection>
   <connection>
      <map_components component_1="intracellular_potassium_concentration" component_2="membrane"/>
      <map_variables variable_1="F" variable_2="F"/>
   </connection>
   <connection>
      <map_components component_1="extracellular_calcium_concentration" component_2="membrane"/>
      <map_variables variable_1="F" variable_2="F"/>
   </connection>
   <connection>
      <map_components component_1="fast_sodium_current" component_2="extracellular_sodium_concentration"/>
      <map_variables variable_1="Na_o" variable_2="Na_o"/>
   </connection>
   <connection>
      <map_components component_1="fast_sodium_current" component_2="intracellular_sodium_concentration"/>
      <map_variables variable_1="Na_i" variable_2="Na_i"/>
      <map_variables variable_1="i_Na" variable_2="i_Na"/>
   </connection>
   <connection>
      <map_components component_1="fast_sodium_current" component_2="extracellular_potassium_concentration"/>
      <map_variables variable_1="K_c" variable_2="K_c"/>
   </connection>
   <connection>
      <map_components component_1="fast_sodium_current" component_2="intracellular_potassium_concentration"/>
      <map_variables variable_1="K_i" variable_2="K_i"/>
   </connection>
   <connection>
      <map_components component_1="sodium_potassium_pump" component_2="intracellular_sodium_concentration"/>
      <map_variables variable_1="Na_i" variable_2="Na_i"/>
      <map_variables variable_1="i_NaK" variable_2="i_NaK"/>
   </connection>
   <connection>
      <map_components component_1="sodium_potassium_pump" component_2="extracellular_potassium_concentration"/>
      <map_variables variable_1="K_c" variable_2="K_c"/>
   </connection>
   <connection>
      <map_components component_1="sodium_potassium_pump" component_2="intracellular_potassium_concentration"/>
      <map_variables variable_1="i_NaK" variable_2="i_NaK"/>
   </connection>
   <connection>
      <map_components component_1="extracellular_calcium_concentration" component_2="Na_Ca_exchanger"/>
      <map_variables variable_1="Ca_o" variable_2="Ca_o"/>
      <map_variables variable_1="i_NaCa" variable_2="i_NaCa"/>
   </connection>
   <connection>
      <map_components component_1="intracellular_calcium_concentration" component_2="Na_Ca_exchanger"/>
      <map_variables variable_1="Ca_i" variable_2="Ca_i"/>
      <map_variables variable_1="i_NaCa" variable_2="i_NaCa"/>
   </connection>
   <connection>
      <map_components component_1="extracellular_sodium_concentration" component_2="Na_Ca_exchanger"/>
      <map_variables variable_1="Na_o" variable_2="Na_o"/>
   </connection>
   <connection>
      <map_components component_1="sodium_background_current" component_2="extracellular_sodium_concentration"/>
      <map_variables variable_1="Na_o" variable_2="Na_o"/>
   </connection>
   <connection>
      <map_components component_1="potassium_background_current" component_2="intracellular_potassium_concentration"/>
      <map_variables variable_1="i_b_K" variable_2="i_b_K"/>
   </connection>
   <connection>
      <map_components component_1="calcium_background_current" component_2="extracellular_calcium_concentration"/>
      <map_variables variable_1="Ca_o" variable_2="Ca_o"/>
      <map_variables variable_1="i_b_Ca" variable_2="i_b_Ca"/>
   </connection>
   <connection>
      <map_components component_1="calcium_background_current" component_2="intracellular_calcium_concentration"/>
      <map_variables variable_1="Ca_i" variable_2="Ca_i"/>
      <map_variables variable_1="i_b_Ca" variable_2="i_b_Ca"/>
   </connection>
   <connection>
      <map_components component_1="time_independent_potassium_current" component_2="extracellular_potassium_concentration"/>
      <map_variables variable_1="K_c" variable_2="K_c"/>
   </connection>
   <connection>
      <map_components component_1="time_independent_potassium_current" component_2="intracellular_potassium_concentration"/>
      <map_variables variable_1="K_i" variable_2="K_i"/>
      <map_variables variable_1="i_K1" variable_2="i_K1"/>
   </connection>
   <connection>
      <map_components component_1="time_independent_potassium_current" component_2="potassium_background_current"/>
      <map_variables variable_1="E_K" variable_2="E_K"/>
   </connection>
   <connection>
      <map_components component_1="second_inward_calcium_current" component_2="extracellular_calcium_concentration"/>
      <map_variables variable_1="Ca_o" variable_2="Ca_o"/>
      <map_variables variable_1="i_siCa" variable_2="i_siCa"/>
   </connection>
   <connection>
      <map_components component_1="second_inward_calcium_current" component_2="extracellular_sodium_concentration"/>
      <map_variables variable_1="Na_o" variable_2="Na_o"/>
   </connection>
   <connection>
      <map_components component_1="second_inward_calcium_current" component_2="intracellular_calcium_concentration"/>
      <map_variables variable_1="Ca_i" variable_2="Ca_i"/>
      <map_variables variable_1="i_siCa" variable_2="i_siCa"/>
   </connection>
   <connection>
      <map_components component_1="second_inward_calcium_current" component_2="extracellular_potassium_concentration"/>
      <map_variables variable_1="K_c" variable_2="K_c"/>
   </connection>
   <connection>
      <map_components component_1="second_inward_calcium_current" component_2="intracellular_potassium_concentration"/>
      <map_variables variable_1="K_i" variable_2="K_i"/>
      <map_variables variable_1="i_siK" variable_2="i_siK"/>
   </connection>
   <connection>
      <map_components component_1="sarcoplasmic_reticulum_calcium_pump" component_2="intracellular_calcium_concentration"/>
      <map_variables variable_1="i_up" variable_2="i_up"/>
      <map_variables variable_1="Ca_i" variable_2="Ca_i"/>
      <map_variables variable_1="Ca_up" variable_2="Ca_up"/>
   </connection>
   <connection>
      <map_components component_1="calcium_release" component_2="intracellular_calcium_concentration"/>
      <map_variables variable_1="i_rel" variable_2="i_rel"/>
      <map_variables variable_1="Ca_i" variable_2="Ca_i"/>
      <map_variables variable_1="Ca_rel" variable_2="Ca_rel"/>
   </connection>
   <connection>
      <map_components component_1="calcium_translocation" component_2="intracellular_calcium_concentration"/>
      <map_variables variable_1="Ca_up" variable_2="Ca_up"/>
      <map_variables variable_1="Ca_rel" variable_2="Ca_rel"/>
      <map_variables variable_1="i_trans" variable_2="i_trans"/>
   </connection>
   <connection>
      <map_components component_1="intracellular_sodium_concentration" component_2="intracellular_calcium_concentration"/>
      <map_variables variable_1="V_i" variable_2="V_i"/>
   </connection>
   <connection>
      <map_components component_1="intracellular_potassium_concentration" component_2="intracellular_calcium_concentration"/>
      <map_variables variable_1="V_i" variable_2="V_i"/>
   </connection>
   <connection>
      <map_components component_1="fast_sodium_current" component_2="fast_sodium_current_m_gate"/>
      <map_variables variable_1="m" variable_2="m"/>
      <map_variables variable_1="time" variable_2="time"/>
      <map_variables variable_1="V" variable_2="V"/>
   </connection>
   <connection>
      <map_components component_1="fast_sodium_current" component_2="fast_sodium_current_h_gate"/>
      <map_variables variable_1="h" variable_2="h"/>
      <map_variables variable_1="time" variable_2="time"/>
      <map_variables variable_1="V" variable_2="V"/>
   </connection>
   <connection>
      <map_components component_1="second_inward_calcium_current" component_2="second_inward_calcium_current_d_gate"/>
      <map_variables variable_1="d" variable_2="d"/>
      <map_variables variable_1="time" variable_2="time"/>
      <map_variables variable_1="V" variable_2="V"/>
   </connection>
   <connection>
      <map_components component_1="second_inward_calcium_current" component_2="second_inward_calcium_current_f_Ca_gate"/>
      <map_variables variable_1="f_Ca" variable_2="f_Ca"/>
      <map_variables variable_1="time" variable_2="time"/>
      <map_variables variable_1="V" variable_2="V"/>
      <map_variables variable_1="Ca_i" variable_2="Ca_i"/>
      <map_variables variable_1="CaChon" variable_2="CaChon"/>
   </connection>
   <connection>
      <map_components component_1="sodium_background_current" component_2="intracellular_sodium_concentration"/>
      <map_variables variable_1="Na_i" variable_2="Na_i"/>
      <map_variables variable_1="i_b_Na" variable_2="i_b_Na"/>
   </connection>
   <connection>
      <map_components component_1="second_inward_calcium_current" component_2="intracellular_sodium_concentration"/>
      <map_variables variable_1="Na_i" variable_2="Na_i"/>
      <map_variables variable_1="i_siNa" variable_2="i_siNa"/>
   </connection>
   <connection>
      <map_components component_1="intracellular_sodium_concentration" component_2="Na_Ca_exchanger"/>
      <map_variables variable_1="Na_i" variable_2="Na_i"/>
      <map_variables variable_1="i_NaCa" variable_2="i_NaCa"/>
   </connection>
   <connection>
      <map_components component_1="extracellular_calcium_concentration" component_2="intracellular_calcium_concentration"/>
      <map_variables variable_1="Ve" variable_2="Ve"/>
   </connection>


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