Location: Hilgemann, Noble, 1987 @ c3ea94a104be / hilgemann_noble_1987.cellml

Author:
Hanne <Hanne@hanne-nielsens-macbook.local>
Date:
2009-12-08 13:41:03+13:00
Desc:
Added images in ai and svg format Removed non pub med references
Permanent Source URI:
https://models.cellml.org/workspace/hilgemann_noble_1987/rawfile/c3ea94a104bef8f00f5f42442006f8375b91ad05/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>Bioengineering Institute, University of Auckland</shortaffil>
    </affiliation>
  </author>
</articleinfo>
  <section id="sec_status">
    <title>Model Status</title>
    <para>
            This model has been curated by Penny Noble of Oxford University and is known to run in PCEnv and COR and reproduce the results published in the paper it is based on.
          </para>
  </section>
  <sect1 id="sec_structure">
<title>Model Structure</title>

<para>
In 1987, D.W. Hilemann and D. Noble published a mathematical model of the atrial action potential.  This built upon the Di Francesco-Noble 1985 model and attempted to correct its main deficiency by considering intracellular calcium buffering.  Although their model was directed towards atrial cells, it also provided a basis for modelling ventricular cells in species (rat, mouse) with short ventricular action potentials.  This model (see the figure below) addressed a number of important questions concerning calcium balance.
</para>

<para>
The complete 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>

<informalfigure float="0" id="fig_cellml_rendering">
<mediaobject>
  <imageobject>
    <objectinfo>
      <title>the cellml rendering of the Hilemann-Noble model</title>
    </objectinfo>
    <imagedata fileref="cellml_rendering.gif"/>
  </imageobject>
</mediaobject>
<caption>The network defined in the CellML description of the Hilemann-Noble model. A key describing the significance of the shapes of the components and the colours of the connections between them is in the <ulink url="${HTML_EXMPL_GRAPHICAL_NOTATION}">notation guide</ulink>.  For simplicity, not all the variables are shown.</caption>
</informalfigure>

<para>
The membrane physically contains the currents, pumps and exchangers as indicated by the blue arrows in <xref linkend="fig_cellml_rendering"/>. The currents act independently and are not connected to each other. Several of the channels encapsulate <emphasis>and</emphasis> contain further components which represent activation and inactivation gates. The addition of an encapsulation relationship informs modellers and processing software that the gates are important parts of the current model. It also prevents any other components that aren't also encapsulated by the parent component from connecting to its gates, effectively hiding them from the rest of the model.
</para>

<para>
The breakdown of the model into components and the definition of encapsulation and containment relationships between them is somewhat arbitrary. When considering how a model should be broken into components, modellers are encouraged to consider which parts of a model might be re-used and how the physiological elements of the system being modelled are naturally bounded. Containment relationships should be used to provide simple rendering information for processing software (ideally, this will correspond to the layout of the physical system), and encapsulation should be used to group sets of components into sub-models.
</para>

</sect1>
</article>
</documentation>
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                                 <ci>gamma</ci>
                                 <apply>
                                    <minus/>
                                    <ci>n_NaCa</ci>
                                    <cn 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 cellml:units="dimensionless">1</cn>
                                 </apply>
                                 <apply>
                                    <minus/>
                                    <ci>n_NaCa</ci>
                                    <cn 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 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 cellml:units="dimensionless">1</cn>
                     <apply>
                        <divide/>
                        <ci>Ca_i</ci>
                        <cn cellml:units="millimolar">0.0069</cn>
                     </apply>
                  </apply>
               </apply>
            </apply>
         </apply>
      </math>
   </component>
   <component name="potassium_background_current">
      <variable units="millivolt" public_interface="in" name="E_K"/>
      <variable units="nanoA" public_interface="out" name="i_b_K"/>
      <variable units="microS" name="g_b_K" initial_value="0.17"/>
      <variable units="second" public_interface="in" name="time"/>
      <variable units="millivolt" public_interface="in" name="V"/>
      <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 units="nanoA" public_interface="out" name="i_K1"/>
      <variable units="millivolt" public_interface="out" name="E_K"/>
      <variable units="microS" name="g_K1" initial_value="1.7"/>
      <variable units="millimolar" name="K_m_K1" initial_value="10"/>
      <variable units="second" public_interface="in" name="time"/>
      <variable units="millivolt" public_interface="in" name="V"/>
      <variable units="millivolt" public_interface="in" name="RTONF"/>
      <variable units="millimolar" public_interface="in" name="K_c"/>
      <variable units="millimolar" public_interface="in" name="K_i"/>
      <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 cellml:units="dimensionless">1</cn>
                  <apply>
                     <exp/>
                     <apply>
                        <divide/>
                        <apply>
                           <times/>
                           <apply>
                              <minus/>
                              <apply>
                                 <minus/>
                                 <ci>V</ci>
                                 <ci>E_K</ci>
                              </apply>
                              <cn cellml:units="millivolt">10</cn>
                           </apply>
                           <cn cellml:units="dimensionless">2</cn>
                        </apply>
                        <ci>RTONF</ci>
                     </apply>
                  </apply>
               </apply>
            </apply>
         </apply>
      </math>
   </component>
   <component name="second_inward_calcium_current">
      <variable units="nanoA" public_interface="out" name="i_si"/>
      <variable units="nanoA" public_interface="out" name="i_siCa"/>
      <variable units="nanoA" public_interface="out" name="i_siK"/>
      <variable units="nanoA" public_interface="out" name="i_siNa"/>
      <variable units="nanoA_per_millimolar" name="P_si" initial_value="5"/>
      <variable units="second" public_interface="in" private_interface="out" name="time"/>
      <variable units="millivolt" public_interface="in" private_interface="out" name="V"/>
      <variable units="millimolar" public_interface="in" private_interface="out" name="Ca_i"/>
      <variable units="millivolt" public_interface="in" name="RTONF"/>
      <variable units="millimolar" public_interface="in" name="Na_i"/>
      <variable units="millimolar" public_interface="in" name="Na_o"/>
      <variable units="millimolar" public_interface="in" name="Ca_o"/>
      <variable units="millimolar" public_interface="in" name="K_i"/>
      <variable units="millimolar" public_interface="in" name="K_c"/>
      <variable units="dimensionless" private_interface="in" name="d"/>
      <variable units="dimensionless" private_interface="in" name="f_Ca"/>
      <variable units="dimensionless" private_interface="in" name="CaChon"/>
      <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 cellml:units="dimensionless">4</cn>
                        <ci>P_si</ci>
                        <ci>d</ci>
                        <ci>CaChon</ci>
                        <apply>
                           <minus/>
                           <ci>V</ci>
                           <cn cellml:units="millivolt">50</cn>
                        </apply>
                     </apply>
                     <ci>RTONF</ci>
                  </apply>
                  <apply>
                     <minus/>
                     <cn cellml:units="dimensionless">1</cn>
                     <apply>
                        <exp/>
                        <apply>
                           <divide/>
                           <apply>
                              <times/>
                              <apply>
                                 <minus/>
                                 <cn cellml:units="dimensionless">1</cn>
                              </apply>
                              <apply>
                                 <minus/>
                                 <ci>V</ci>
                                 <cn cellml:units="millivolt">50</cn>
                              </apply>
                              <cn 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 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 cellml:units="dimensionless">2</cn>
                              </apply>
                              <apply>
                                 <minus/>
                                 <ci>V</ci>
                                 <cn 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 cellml:units="dimensionless">0.002</cn>
                        <ci>P_si</ci>
                        <ci>d</ci>
                        <ci>CaChon</ci>
                        <apply>
                           <minus/>
                           <ci>V</ci>
                           <cn cellml:units="millivolt">50</cn>
                        </apply>
                     </apply>
                     <ci>RTONF</ci>
                  </apply>
                  <apply>
                     <minus/>
                     <cn cellml:units="dimensionless">1</cn>
                     <apply>
                        <exp/>
                        <apply>
                           <divide/>
                           <apply>
                              <times/>
                              <apply>
                                 <minus/>
                                 <cn cellml:units="dimensionless">1</cn>
                              </apply>
                              <apply>
                                 <minus/>
                                 <ci>V</ci>
                                 <cn 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 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 cellml:units="dimensionless">1</cn>
                              </apply>
                              <apply>
                                 <minus/>
                                 <ci>V</ci>
                                 <cn 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 cellml:units="dimensionless">0.01</cn>
                        <ci>P_si</ci>
                        <ci>d</ci>
                        <ci>CaChon</ci>
                        <apply>
                           <minus/>
                           <ci>V</ci>
                           <cn cellml:units="millivolt">50</cn>
                        </apply>
                     </apply>
                     <ci>RTONF</ci>
                  </apply>
                  <apply>
                     <minus/>
                     <cn cellml:units="dimensionless">1</cn>
                     <apply>
                        <exp/>
                        <apply>
                           <divide/>
                           <apply>
                              <times/>
                              <apply>
                                 <minus/>
                                 <cn cellml:units="dimensionless">1</cn>
                              </apply>
                              <apply>
                                 <minus/>
                                 <ci>V</ci>
                                 <cn 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 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 cellml:units="dimensionless">1</cn>
                              </apply>
                              <apply>
                                 <minus/>
                                 <ci>V</ci>
                                 <cn cellml:units="millivolt">50</cn>
                              </apply>
                           </apply>
                           <ci>RTONF</ci>
                        </apply>
                     </apply>
                  </apply>
               </apply>
            </apply>
         </apply>
      </math>
   </component>
   <component name="second_inward_calcium_current_d_gate">
      <variable units="dimensionless" public_interface="out" name="d" initial_value="0.0011"/>
      <variable units="per_second" name="alpha_d"/>
      <variable units="per_second" name="beta_d"/>
      <variable units="millivolt" public_interface="in" name="V"/>
      <variable units="second" public_interface="in" name="time"/>
      <variable units="millivolt" name="delta_d" initial_value="0.0001"/>
      <variable units="millivolt" name="E0_d"/>
      <math xmlns="http://www.w3.org/1998/Math/MathML">
         <apply>
            <eq/>
            <ci>E0_d</ci>
            <apply>
               <minus/>
               <apply>
                  <plus/>
                  <ci>V</ci>
                  <cn cellml:units="millivolt">24</cn>
               </apply>
               <cn cellml:units="millivolt">5</cn>
            </apply>
         </apply>
         <apply>
            <eq/>
            <ci>alpha_d</ci>
            <piecewise>
               <piece>
                  <cn 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 cellml:units="per_millivolt_second">30</cn>
                        <ci>E0_d</ci>
                     </apply>
                     <apply>
                        <minus/>
                        <cn cellml:units="dimensionless">1</cn>
                        <apply>
                           <exp/>
                           <apply>
                              <divide/>
                              <apply>
                                 <times/>
                                 <apply>
                                    <minus/>
                                    <cn cellml:units="dimensionless">1</cn>
                                 </apply>
                                 <ci>E0_d</ci>
                              </apply>
                              <cn cellml:units="millivolt">4</cn>
                           </apply>
                        </apply>
                     </apply>
                  </apply>
               </otherwise>
            </piecewise>
         </apply>
         <apply>
            <eq/>
            <ci>beta_d</ci>
            <piecewise>
               <piece>
                  <cn 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 cellml:units="per_millivolt_second">12</cn>
                        <ci>E0_d</ci>
                     </apply>
                     <apply>
                        <minus/>
                        <apply>
                           <exp/>
                           <apply>
                              <divide/>
                              <ci>E0_d</ci>
                              <cn cellml:units="millivolt">10</cn>
                           </apply>
                        </apply>
                        <cn 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 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 name="second_inward_calcium_current_f_Ca_gate">
      <variable units="dimensionless" public_interface="out" name="f_Ca" initial_value="0.785"/>
      <variable units="per_second" name="alpha_f_Ca"/>
      <variable units="per_second" name="beta_f_Ca"/>
      <variable units="dimensionless" name="CaChoff"/>
      <variable units="dimensionless" public_interface="out" name="CaChon"/>
      <variable units="millivolt" public_interface="in" name="V"/>
      <variable units="second" public_interface="in" name="time"/>
      <variable units="millimolar" public_interface="in" name="Ca_i"/>
      <variable units="millivolt" name="delta_f" initial_value="0.0001"/>
      <variable units="millivolt" name="E0_f"/>
      <math xmlns="http://www.w3.org/1998/Math/MathML">
         <apply>
            <eq/>
            <ci>E0_f</ci>
            <apply>
               <plus/>
               <ci>V</ci>
               <cn cellml:units="millivolt">34</cn>
            </apply>
         </apply>
         <apply>
            <eq/>
            <ci>alpha_f_Ca</ci>
            <piecewise>
               <piece>
                  <cn 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 cellml:units="per_millivolt_second">6.25</cn>
                        <ci>E0_f</ci>
                     </apply>
                     <apply>
                        <minus/>
                        <apply>
                           <exp/>
                           <apply>
                              <divide/>
                              <ci>E0_f</ci>
                              <cn cellml:units="millivolt">4</cn>
                           </apply>
                        </apply>
                        <cn cellml:units="dimensionless">1</cn>
                     </apply>
                  </apply>
               </otherwise>
            </piecewise>
         </apply>
         <apply>
            <eq/>
            <ci>beta_f_Ca</ci>
            <apply>
               <divide/>
               <cn cellml:units="per_second">12</cn>
               <apply>
                  <plus/>
                  <cn cellml:units="dimensionless">1</cn>
                  <apply>
                     <exp/>
                     <apply>
                        <divide/>
                        <apply>
                           <minus/>
                           <ci>E0_f</ci>
                        </apply>
                        <cn 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 cellml:units="dimensionless">120</cn>
                        <apply>
                           <minus/>
                           <cn cellml:units="dimensionless">1</cn>
                           <ci>f_Ca</ci>
                        </apply>
                        <ci>CaChoff</ci>
                     </apply>
                     <apply>
                        <times/>
                        <apply>
                           <minus/>
                           <cn cellml:units="dimensionless">1</cn>
                           <ci>f_Ca</ci>
                        </apply>
                        <apply>
                           <minus/>
                           <cn 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 cellml:units="millimolar">0.001</cn>
                  <ci>Ca_i</ci>
               </apply>
            </apply>
         </apply>
         <apply>
            <eq/>
            <ci>CaChon</ci>
            <apply>
               <times/>
               <apply>
                  <minus/>
                  <cn cellml:units="dimensionless">1</cn>
                  <ci>f_Ca</ci>
               </apply>
               <apply>
                  <minus/>
                  <cn cellml:units="dimensionless">1</cn>
                  <ci>CaChoff</ci>
               </apply>
            </apply>
         </apply>
      </math>
   </component>
   <component name="sarcoplasmic_reticulum_calcium_pump">
      <variable units="millimolar_per_second" public_interface="out" name="i_up"/>
      <variable units="dimensionless" name="K_1"/>
      <variable units="millimolar" name="K_2"/>
      <variable units="millimolar" name="K_cyca" initial_value="0.0003"/>
      <variable units="dimensionless" name="K_xcs" initial_value="0.4"/>
      <variable units="millimolar" name="K_srca" initial_value="0.5"/>
      <variable units="millimolar_per_second" name="alpha_up" initial_value="3"/>
      <variable units="millimolar_per_second" name="beta_up" initial_value="0.23"/>
      <variable units="millimolar" public_interface="in" name="Ca_up"/>
      <variable units="second" public_interface="in" name="time"/>
      <variable units="millimolar" public_interface="in" name="Ca_i"/>
      <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 units="millimolar_per_second" public_interface="out" name="i_rel" cmeta:id="calcium_release_i_rel"/>
      <variable units="dimensionless" name="VoltDep"/>
      <variable units="dimensionless" name="RegBindSite"/>
      <variable units="per_second" name="ActRate"/>
      <variable units="per_second" name="InactRate"/>
      <variable units="per_second" name="K_leak_rate" initial_value="0"/>
      <variable units="per_second" name="K_m_rel" initial_value="250"/>
      <variable units="dimensionless" name="PrecFrac"/>
      <variable units="dimensionless" name="ActFrac" initial_value="0"/>
      <variable units="dimensionless" name="ProdFrac" initial_value="0"/>
      <variable units="second" public_interface="in" name="time"/>
      <variable units="millivolt" public_interface="in" name="V"/>
      <variable units="millimolar" public_interface="in" name="Ca_i"/>
      <variable units="millimolar" public_interface="in" name="Ca_rel"/>
      <math xmlns="http://www.w3.org/1998/Math/MathML">
         <apply>
            <eq/>
            <ci>PrecFrac</ci>
            <apply>
               <minus/>
               <apply>
                  <minus/>
                  <cn cellml:units="dimensionless">1</cn>
                  <ci>ActFrac</ci>
               </apply>
               <ci>ProdFrac</ci>
            </apply>
         </apply>
         <apply>
            <eq/>
            <ci>VoltDep</ci>
            <apply>
               <exp/>
               <apply>
                  <times/>
                  <cn cellml:units="per_millivolt">0.08</cn>
                  <apply>
                     <minus/>
                     <ci>V</ci>
                     <cn 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 cellml:units="millimolar">0.0005</cn>
                  </apply>
               </apply>
               <cn cellml:units="dimensionless">2</cn>
            </apply>
         </apply>
         <apply>
            <eq/>
            <ci>ActRate</ci>
            <apply>
               <plus/>
               <apply>
                  <times/>
                  <cn cellml:units="per_second">600</cn>
                  <ci>VoltDep</ci>
               </apply>
               <apply>
                  <times/>
                  <cn cellml:units="per_second">500</cn>
                  <ci>RegBindSite</ci>
               </apply>
            </apply>
         </apply>
         <apply>
            <eq/>
            <ci>InactRate</ci>
            <apply>
               <plus/>
               <cn cellml:units="per_second">60</cn>
               <apply>
                  <times/>
                  <cn 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 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 cellml:units="dimensionless">0.25</cn>
                           </apply>
                        </apply>
                        <cn 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 units="millimolar_per_second" public_interface="out" name="i_trans" cmeta:id="calcium_translocation_i_trans"/>
      <variable units="millimolar" public_interface="in" name="Ca_rel"/>
      <variable units="millimolar" public_interface="in" name="Ca_up"/>
      <variable units="per_second" name="alpha_tr" initial_value="50"/>
      <variable units="second" public_interface="in" name="time"/>
      <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 name="extracellular_sodium_concentration">
      <variable units="millimolar" public_interface="out" name="Na_o" initial_value="140"/>
   </component>
   <component name="intracellular_sodium_concentration">
      <variable units="millimolar" public_interface="out" name="Na_i" initial_value="6.5"/>
      <variable units="micrometre3" public_interface="in" name="V_i"/>
      <variable units="second" public_interface="in" name="time"/>
      <variable units="coulomb_per_mole" public_interface="in" name="F"/>
      <variable units="nanoA" public_interface="in" name="i_Na"/>
      <variable units="nanoA" public_interface="in" name="i_b_Na"/>
      <variable units="nanoA" public_interface="in" name="i_siNa"/>
      <variable units="nanoA" public_interface="in" name="i_NaK"/>
      <variable units="nanoA" public_interface="in" name="i_NaCa"/>
      <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 cellml:units="mA_nA">1</cn>
                  </apply>
                  <apply>
                     <times/>
                     <cn 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 cellml:units="dimensionless">3</cn>
                  </apply>
                  <apply>
                     <times/>
                     <ci>i_NaCa</ci>
                     <cn cellml:units="dimensionless">3</cn>
                  </apply>
                  <ci>i_siNa</ci>
               </apply>
            </apply>
         </apply>
      </math>
   </component>
   <component name="extracellular_calcium_concentration">
      <variable units="millimolar" public_interface="out" name="Ca_o" initial_value="2"/>
      <variable units="nanoA" public_interface="in" name="i_NaCa"/>
      <variable units="millimolar" name="Cab" initial_value="2"/>
      <variable units="per_second" name="K_diff" initial_value="0.0005"/>
      <variable units="micrometre3" public_interface="in" name="Ve"/>
      <variable units="coulomb_per_mole" public_interface="in" name="F"/>
      <variable units="second" public_interface="in" name="time"/>
      <variable units="nanoA" public_interface="in" name="i_siCa"/>
      <variable units="nanoA" public_interface="in" name="i_b_Ca"/>
      <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 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 cellml:units="dimensionless">2</cn>
                     <cn cellml:units="litre_micrometre3">1</cn>
                     <ci>Ve</ci>
                     <ci>F</ci>
                  </apply>
               </apply>
            </apply>
         </apply>
      </math>
   </component>
   <component name="extracellular_potassium_concentration">
      <variable units="millimolar" public_interface="out" name="K_c" initial_value="4"/>
   </component>
   <component name="intracellular_potassium_concentration">
      <variable units="millimolar" public_interface="out" name="K_i" initial_value="140"/>
      <variable units="micrometre3" public_interface="in" name="V_i"/>
      <variable units="nanoA" public_interface="in" name="i_K1"/>
      <variable units="nanoA" public_interface="in" name="i_siK"/>
      <variable units="nanoA" public_interface="in" name="i_b_K"/>
      <variable units="nanoA" public_interface="in" name="i_NaK"/>
      <variable units="second" public_interface="in" name="time"/>
      <variable units="coulomb_per_mole" public_interface="in" name="F"/>
      <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 cellml:units="mA_nA">1</cn>
                  </apply>
                  <apply>
                     <times/>
                     <cn 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 cellml:units="dimensionless">2</cn>
                     <ci>i_NaK</ci>
                  </apply>
               </apply>
            </apply>
         </apply>
      </math>
   </component>
   <component name="intracellular_calcium_concentration">
      <variable units="millimolar" public_interface="out" cmeta:id="intracellular_calcium_concentration_Ca_i" name="Ca_i" initial_value="1e-5"/>
      <variable units="millimolar" public_interface="out" name="Ca_up" initial_value="0.3"/>
      <variable units="millimolar" public_interface="out" name="Ca_rel" initial_value="0.3"/>
      <variable units="millimolar" name="Ca_Calmod" initial_value="0.0005"/>
      <variable units="millimolar" name="Ca_Trop" initial_value="0.0015"/>
      <variable units="millimolar" name="Calmod" initial_value="0.02"/>
      <variable units="millimolar" name="Trop" initial_value="0.15"/>
      <variable units="per_millimolar_second" name="alpha_Calmod" initial_value="100000"/>
      <variable units="per_second" name="beta_Calmod" initial_value="50"/>
      <variable units="per_millimolar_second" name="alpha_Trop" initial_value="100000"/>
      <variable units="per_second" name="beta_Trop" initial_value="200"/>
      <variable units="micrometre" name="radius" initial_value="0.08"/>
      <variable units="micrometre" name="length" initial_value="0.08"/>
      <variable units="micrometre3" public_interface="out" name="V_i"/>
      <variable units="micrometre3" public_interface="out" name="Ve"/>
      <variable units="micrometre3" name="V_Cell"/>
      <variable units="dimensionless" name="V_i_ratio"/>
      <variable units="dimensionless" name="V_rel_ratio" initial_value="0.1"/>
      <variable units="dimensionless" name="V_e_ratio" initial_value="0.4"/>
      <variable units="dimensionless" name="V_up_ratio" initial_value="0.01"/>
      <variable units="millimolar_per_second" public_interface="in" name="i_up"/>
      <variable units="millimolar_per_second" public_interface="in" name="i_trans"/>
      <variable units="millimolar_per_second" public_interface="in" name="i_rel"/>
      <variable units="nanoA" public_interface="in" name="i_NaCa"/>
      <variable units="nanoA" public_interface="in" name="i_siCa"/>
      <variable units="nanoA" public_interface="in" name="i_b_Ca"/>
      <variable units="coulomb_per_mole" public_interface="in" name="F"/>
      <variable units="second" public_interface="in" name="time"/>
      <math xmlns="http://www.w3.org/1998/Math/MathML">
         <apply>
            <eq/>
            <ci>V_Cell</ci>
            <apply>
               <times/>
               <cn cellml:units="dimensionless">3.141592654</cn>
               <apply>
                  <power/>
                  <ci>radius</ci>
                  <cn 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 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 cellml:units="mA_nA">1</cn>
                    </apply>
                    <apply>
                      <times/>
                      <cn cellml:units="dimensionless">2</cn>
                      <cn 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 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 units="millimolar_per_second" name="dCaCalmoddt"/>
    <variable units="millimolar_per_second" name="dCaTropdt"/>
  </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_2="environment" component_1="membrane"/>
      <map_variables variable_2="time" variable_1="time"/>
   </connection>
   <connection>
      <map_components component_2="environment" component_1="fast_sodium_current"/>
      <map_variables variable_2="time" variable_1="time"/>
   </connection>
   <connection>
      <map_components component_2="environment" component_1="sodium_potassium_pump"/>
      <map_variables variable_2="time" variable_1="time"/>
   </connection>
   <connection>
      <map_components component_2="environment" component_1="sodium_background_current"/>
      <map_variables variable_2="time" variable_1="time"/>
   </connection>
   <connection>
      <map_components component_2="environment" component_1="calcium_background_current"/>
      <map_variables variable_2="time" variable_1="time"/>
   </connection>
   <connection>
      <map_components component_2="environment" component_1="potassium_background_current"/>
      <map_variables variable_2="time" variable_1="time"/>
   </connection>
   <connection>
      <map_components component_2="environment" component_1="Na_Ca_exchanger"/>
      <map_variables variable_2="time" variable_1="time"/>
   </connection>
   <connection>
      <map_components component_2="environment" component_1="time_independent_potassium_current"/>
      <map_variables variable_2="time" variable_1="time"/>
   </connection>
   <connection>
      <map_components component_2="environment" component_1="second_inward_calcium_current"/>
      <map_variables variable_2="time" variable_1="time"/>
   </connection>
   <connection>
      <map_components component_2="environment" component_1="sarcoplasmic_reticulum_calcium_pump"/>
      <map_variables variable_2="time" variable_1="time"/>
   </connection>
   <connection>
      <map_components component_2="environment" component_1="calcium_release"/>
      <map_variables variable_2="time" variable_1="time"/>
   </connection>
   <connection>
      <map_components component_2="environment" component_1="calcium_translocation"/>
      <map_variables variable_2="time" variable_1="time"/>
   </connection>
   <connection>
      <map_components component_2="environment" component_1="extracellular_calcium_concentration"/>
      <map_variables variable_2="time" variable_1="time"/>
   </connection>
   <connection>
      <map_components component_2="environment" component_1="intracellular_calcium_concentration"/>
      <map_variables variable_2="time" variable_1="time"/>
   </connection>
   <connection>
      <map_components component_2="environment" component_1="intracellular_sodium_concentration"/>
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    <dc:title>Proceedings of the Royal Society of London - Series B</dc:title>
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