Location: Faville, Pullan, Sanders, Smith, 2008 @ 19e3365b8f8c / faville_pullan_sanders_smith_2008.cellml

Author:
pmr2.import <nobody@models.cellml.org>
Date:
2008-03-25 03:42:26+13:00
Desc:
committing version02 of faville_pullan_sanders_smith_2008
Permanent Source URI:
https://models.cellml.org/workspace/faville_pullan_sanders_smith_2008/rawfile/19e3365b8f8cee2041ce1cfd1e61d690416d9d9b/faville_pullan_sanders_smith_2008.cellml

<?xml version='1.0' encoding='utf-8'?>
<!--  FILE :  faville_model_2008.xml

CREATED :  4th October 2007

LAST MODIFIED : 20th March 2008

AUTHOR :  Catherine Lloyd
          Bioengineering Institute
          The University of Auckland
          
MODEL STATUS :  This model conforms to the CellML 1.1 Specification.

DESCRIPTION :  This file contains a CellML description of Richard Faville et al.'s 2008 biophysically based mathematical model of unitary potential activity in interstitial cells of Cajal.

CHANGES:  
  
--><model xmlns="http://www.cellml.org/cellml/1.0#" xmlns:cmeta="http://www.cellml.org/metadata/1.0#" xmlns:dc="http://purl.org/dc/elements/1.1/" xmlns:rdf="http://www.w3.org/1999/02/22-rdf-syntax-ns#" xmlns:bqs="http://www.cellml.org/bqs/1.0#" xmlns:cellml="http://www.cellml.org/cellml/1.0#" xmlns:dcterms="http://purl.org/dc/terms/" xmlns:vCard="http://www.w3.org/2001/vcard-rdf/3.0#" cmeta:id="faville_model_2008" name="faville_model_2008">

<documentation xmlns="http://cellml.org/tmp-documentation">
<article>
  <articleinfo>
  <title>A Biophysically Based Mathematical Model of Unitary Potential Activity in Interstitial Cells of Cajal</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 CellML model is known to run in both COR and PCEnv to replicate the published results.  The units have been checked and are consistent.  We'd like to acknowledge Richard Faville for his help in getting the CellML model to replicate his published model.
          </para>
  </section>
  <sect1 id="sec_structure">
  <title>Model Structure</title>

<para>
Phasic gastrointestinal (GI) muscle is able to autonomously generate rhythmic contractions independent of the enteric nervous system.  The electrical activity that generates these rhythmic contractions are called slow waves, or pacemaker potentials (PP), and they are produced by a specialised group of pacemaker cells called Interstitial Cells of Cajal (ICC).  They pass via gap junctions from the ICC to smooth muscle cells (SMC), activating L-type Ca2+ channels, Ca2+ influx and the contraction of the SMC.  Full slow waves result from the summation of a large number of localised cellular membrane fluctuations, and are know as unitary potentials (UPs).  These are generated at intracellular sites called pacemaker units, and are known to play an essential role in driving the coordinated contraction of GI muscles. 
</para>

<para>
In the study described here, Richard Faville <emphasis>et al.</emphasis> have developed a mathematical model which quantitatively describes the transmembrane ion flows and intracellular Ca2+ dynamics from a single ICC pacemaker unit.  They have combined experimental data with a theoretical hypothesis to produce a biophysically-based computational modelling framework that simulates ICC pacemaker activity on the pacemaker unit spatial scale.
</para>

<informalfigure float="0" id="fig_reaction_diagram">
<mediaobject>
  <imageobject>
    <objectinfo>
      <title>model diagram</title>
    </objectinfo>
    <imagedata fileref="faville_2008.png"/>
  </imageobject>
</mediaobject>
<caption>A schematic diagram of the pacemaker unit illustrating all the compartmental volumes and ionic conductances, together with their interactions.</caption>
</informalfigure>

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

<para>
<ulink url="http://www.springerlink.com/content/652t4456624w2502/">A Biophysically Based Mathematical Model of Unitary Potential Activity in Interstitial Cells of Cajal</ulink>, R.A. Faville, A.J. Pullan, K.M. Sanders, and N.P. Smith, 2008, <ulink url="http://www.biophysj.org/">
            <emphasis>Biophysical Journal</emphasis>
          </ulink>.  (A <ulink url="http://www.biophysj.org/cgi/rapidpdf/biophysj.107.122507v1">PDF</ulink> version of the article are available to journal subscribers on the <emphasis>Biophysical Journal</emphasis> website.)  <ulink url="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&amp;cmd=Retrieve&amp;dopt=AbstractPlus&amp;list_uids=18339738&amp;query_hl=1&amp;itool=pubmed_docsum">PubMed ID: 18339738</ulink>
</para>

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



 
 
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        <dcterms:alternative>plasma membrane Ca2+-ATPase current</dcterms:alternative>  
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    </math>
  </component>

  <component cmeta:id="JIPR" name="JIPR">
    <rdf:RDF xmlns:rdf="http://www.w3.org/1999/02/22-rdf-syntax-ns#">
      <rdf:Description rdf:about="JIPR">
        <dc:title>JIPR</dc:title>
        <dcterms:alternative>IP3R Ca2+ flux</dcterms:alternative>  
      </rdf:Description>
    </rdf:RDF>  
    <variable units="flux" public_interface="out" name="JIPR"/>
    
    <variable units="first_order_rate_constant" name="kIPR" initial_value="2000.0"/>
    <variable units="flux" name="k_1" initial_value="6.4"/>
    <variable units="first_order_rate_constant" name="k1" initial_value="0.0"/>
    <variable units="first_order_rate_constant" name="k2" initial_value="4.0"/>
    <variable units="first_order_rate_constant" name="r2" initial_value="200.0"/>
    <variable units="flux" name="r_2" initial_value="0.0"/>
    <variable units="first_order_rate_constant" name="r4" initial_value="750.0"/>
    <variable units="micromolar" name="R1" initial_value="36.0"/>      
    <variable units="micromolar" name="R3" initial_value="300.0"/>
    <variable units="first_order_rate_constant" name="phi1"/>
    <variable units="flux" name="phi_1"/>
    <variable units="first_order_rate_constant" name="phi2"/>
    <variable units="first_order_rate_constant" name="phi3" initial_value="0.306"/> 
    <variable units="dimensionless" name="H" initial_value="0.787"/>
    <variable units="first_order_rate_constant" name="g_beta" initial_value="300.0"/>
    <variable units="dimensionless" name="h_beta" initial_value="2.0"/>
    <variable units="per_second_squared" name="g_alpha" initial_value="0.02"/>
    <variable units="micromolar" name="K_beta" initial_value="2.0"/>
    <variable units="per_second_squared" name="alpha_phi3"/>
    <variable units="first_order_rate_constant" name="beta_phi3"/>
    
    <variable units="micromolar" public_interface="in" name="CER"/>
    <variable units="micromolar" public_interface="in" name="CS2"/>
    <variable units="micromolar" public_interface="in" name="P"/>
    <variable units="second" public_interface="in" name="time"/>
    
    <math xmlns="http://www.w3.org/1998/Math/MathML">
      <apply>
        <eq/> 
        <apply>
          <diff/> 
          <bvar>
            <ci>time</ci>
          </bvar> 
          <ci> H </ci> 
        </apply>
        <apply>
          <minus/>
          <apply>
            <times/>
            <ci> phi3 </ci>
            <apply>
              <minus/>
              <cn cellml:units="dimensionless"> 1.0 </cn>
              <ci> H </ci>
            </apply>
          </apply>
          <apply>
            <times/>
            <apply>
              <divide/>
              <apply>
                <times/>
                <ci> P </ci>
                <ci> phi1 </ci>
                <ci> phi2 </ci>
              </apply>
              <apply>
                <plus/>
                <apply>
                  <times/>
                  <ci> P </ci>
                  <ci> phi1 </ci>
                </apply>
                <ci> phi_1 </ci>
              </apply>
            </apply>
            <ci> H </ci>
          </apply>
        </apply>
      </apply>

      <apply>
        <eq/>
        <ci> JIPR </ci>
        <apply>
          <times/>
          <ci> kIPR </ci>
          <apply>
            <power/>
            <apply>
              <divide/>
              <apply>
                <times/>
                <ci> P </ci>
                <ci> phi1 </ci>
                <ci> H </ci>
              </apply>
              <apply>
                <plus/>
                <apply>
                  <times/>
                  <ci> P </ci>
                  <ci> phi1 </ci>
                </apply>
                <ci> phi_1 </ci>
              </apply>
            </apply>
            <cn cellml:units="dimensionless"> 4.0 </cn>
          </apply>
          <apply>
            <minus/>
            <ci> CER </ci>
            <ci> CS2 </ci>
          </apply>
        </apply>
      </apply>

      <apply>
        <eq/>
        <ci> phi1 </ci>
        <apply>
          <divide/>
          <apply>
            <plus/>
            <apply>
              <times/>
              <ci> k1 </ci>
              <ci> R1 </ci>
            </apply>
            <apply>
              <times/>
              <ci> r2 </ci>
              <ci> CS2 </ci>
            </apply>
          </apply>
          <apply>
            <plus/>
            <ci> R1 </ci>
            <ci> CS2 </ci>
          </apply>
        </apply>
      </apply>

      <apply>
        <eq/>
        <ci> phi_1 </ci>
        <apply>
          <divide/>
          <apply>
            <times/>
            <apply>
              <plus/>
              <ci> k_1 </ci>
              <ci> r_2 </ci>
            </apply>
            <ci> R3 </ci>
          </apply>
          <apply>
            <plus/>
            <ci> R3 </ci>
            <ci> CS2 </ci>
          </apply>
        </apply>
      </apply>

      <apply>
        <eq/>
        <ci> phi2 </ci>
        <apply>
          <divide/>
          <apply>
            <plus/>
            <apply>
              <times/>
              <ci> k2 </ci>
              <ci> R3 </ci>
            </apply>
            <apply>
              <times/>
              <ci> r4 </ci>
              <ci> CS2 </ci>
            </apply>
          </apply>
          <apply>
            <plus/>
            <ci> R3 </ci>
            <ci> CS2 </ci>
          </apply>
        </apply>
      </apply>

      <apply>
        <eq/> 
        <apply>
          <diff/> 
          <bvar>
            <ci>time</ci>
          </bvar> 
          <ci> phi3 </ci> 
        </apply>
        <apply>
          <minus/>
          <ci> alpha_phi3 </ci>
          <apply>
            <times/>
            <ci> beta_phi3 </ci>
            <ci> phi3 </ci>
          </apply>
        </apply>
      </apply>

      <apply>
        <eq/>
        <ci> alpha_phi3 </ci>
        <ci> g_alpha </ci>
      </apply>

      <apply>
        <eq/>
        <ci> beta_phi3 </ci>
        <apply>
          <times/>
          <ci> g_beta </ci>
          <apply>
            <divide/>
            <apply>
              <power/>
              <ci> CS2 </ci>
              <ci> h_beta </ci>
            </apply>
            <apply>
              <plus/>
              <apply>
                <power/>
                <ci> K_beta </ci>
                <ci> h_beta </ci>
              </apply>
              <apply>
                <power/>
                <ci> CS2 </ci>
                <ci> h_beta </ci>
              </apply>
            </apply>
          </apply>
        </apply>
      </apply>
    </math>
  </component>

  <component cmeta:id="CS1" name="CS1">
    <rdf:RDF xmlns:rdf="http://www.w3.org/1999/02/22-rdf-syntax-ns#">
      <rdf:Description rdf:about="CS1">
        <dc:title>CS1</dc:title>
        <dcterms:alternative>calcium concentration in cytoplasmic subspace 1</dcterms:alternative>  
      </rdf:Description>
    </rdf:RDF>  
    <variable units="micromolar" public_interface="out" name="CS1" initial_value="0.120"/>
    
    <variable units="dimensionless" name="lambda_MT_S1"/>
    <variable units="dimensionless" name="lambda_ER_S1"/>      
    
    <variable units="flux" public_interface="in" name="JS1S2"/>
    <variable units="flux" public_interface="in" name="JNCX"/>
    <variable units="flux" public_interface="in" name="JSERCA"/>
    <variable units="picoampere" public_interface="in" name="I_iCa"/>
    <variable units="micromolar_coulomb" public_interface="in" name="delta_s"/>
    <variable units="dimensionless" public_interface="in" name="gamma_S1"/>
    <variable units="dimensionless" public_interface="in" name="gamma_MT"/>
    <variable units="dimensionless" public_interface="in" name="gamma_ER"/>
    <variable units="second" public_interface="in" name="time"/>
    
    <math xmlns="http://www.w3.org/1998/Math/MathML">
      <apply>
        <eq/> 
        <apply>
          <diff/> 
          <bvar>
            <ci>time</ci>
          </bvar> 
          <ci> CS1 </ci> 
        </apply>
        <apply>
          <minus/>
          <apply>
            <plus/>
            <ci> JS1S2 </ci>
            <apply>
              <times/>
              <ci> lambda_MT_S1 </ci>
              <ci> JNCX </ci>
            </apply>
          </apply>
          <apply>
            <plus/>
            <apply>
              <times/>
              <apply>
                <divide/>
                <ci> delta_s </ci>
                <cn cellml:units="dimensionless"> 2.0 </cn>
              </apply>
              <ci> I_iCa </ci>
            </apply>
            <apply>
              <times/>
              <ci> lambda_ER_S1 </ci>
              <ci> JSERCA </ci>
            </apply>
          </apply>
        </apply>
      </apply>

      <apply>
        <eq/>
        <ci> lambda_MT_S1 </ci>
        <apply>
          <divide/>
          <ci> gamma_MT </ci>
          <ci> gamma_S1 </ci>
        </apply>
      </apply>

      <apply>
        <eq/>
        <ci> lambda_ER_S1 </ci>
        <apply>
          <divide/>
          <ci> gamma_ER </ci>
          <ci> gamma_S1 </ci>
        </apply>
      </apply>
    </math>
  </component>

  <component cmeta:id="CS2" name="CS2">
    <rdf:RDF xmlns:rdf="http://www.w3.org/1999/02/22-rdf-syntax-ns#">
      <rdf:Description rdf:about="CS2">
        <dc:title>CS2</dc:title>
        <dcterms:alternative>calcium concentration in cytoplasmic subspace 2</dcterms:alternative>  
      </rdf:Description>
    </rdf:RDF>  
    <variable units="micromolar" public_interface="out" name="CS2" initial_value="0.023"/>
    
    <variable units="dimensionless" name="lambda_MT_S2"/>
    <variable units="dimensionless" name="lambda_ER_S2"/>
    <variable units="dimensionless" name="lambda_S1_S2"/>      
    
    <variable units="flux" public_interface="in" name="JS1S2"/>
    <variable units="flux" public_interface="in" name="JMCU"/>
    <variable units="flux" public_interface="in" name="JIPR"/>
    <variable units="dimensionless" public_interface="in" name="gamma_S1"/>
    <variable units="dimensionless" public_interface="in" name="gamma_S2"/>
    <variable units="dimensionless" public_interface="in" name="gamma_MT"/>
    <variable units="dimensionless" public_interface="in" name="gamma_ER"/>
    <variable units="second" public_interface="in" name="time"/>
    
    <math xmlns="http://www.w3.org/1998/Math/MathML">
      <apply>
        <eq/> 
        <apply>
          <diff/> 
          <bvar>
            <ci>time</ci>
          </bvar> 
          <ci> CS2 </ci> 
        </apply>
        <apply>
          <minus/>
          <apply>
            <times/>
            <ci> lambda_ER_S2 </ci>
            <ci> JIPR </ci>
          </apply>
          <apply>
            <plus/>
            <apply>
              <times/>
              <ci> lambda_S1_S2 </ci>
              <ci> JS1S2 </ci>
            </apply>
            <apply>
              <times/>
              <ci> lambda_MT_S2 </ci>
              <ci> JMCU </ci>
            </apply>
          </apply>
        </apply>
      </apply>

      <apply>
        <eq/>
        <ci> lambda_MT_S2 </ci>
        <apply>
          <divide/>
          <ci> gamma_MT </ci>
          <ci> gamma_S2 </ci>
        </apply>
      </apply>

      <apply>
        <eq/>
        <ci> lambda_ER_S2 </ci>
        <apply>
          <divide/>
          <ci> gamma_ER </ci>
          <ci> gamma_S2 </ci>
        </apply>
      </apply>

      <apply>
        <eq/>
        <ci> lambda_S1_S2 </ci>
        <apply>
          <divide/>
          <ci> gamma_S1 </ci>
          <ci> gamma_S2 </ci>
        </apply>
      </apply>
    </math>
  </component>

  <component cmeta:id="CER" name="CER">
    <rdf:RDF xmlns:rdf="http://www.w3.org/1999/02/22-rdf-syntax-ns#">
      <rdf:Description rdf:about="CER">
        <dc:title>CER</dc:title>
        <dcterms:alternative>calcium concentration in the endoplasmic reticulum</dcterms:alternative>  
      </rdf:Description>
    </rdf:RDF>  
    <variable units="micromolar" public_interface="out" name="CER" initial_value="203.0"/>
    
    <variable units="flux" public_interface="in" name="JSERCA"/>
    <variable units="flux" public_interface="in" name="JIPR"/>
    <variable units="second" public_interface="in" name="time"/>
    
    <math xmlns="http://www.w3.org/1998/Math/MathML">
      <apply>
        <eq/> 
        <apply>
          <diff/> 
          <bvar>
            <ci>time</ci>
          </bvar> 
          <ci> CER </ci> 
        </apply>
        <apply>
          <minus/>
          <ci> JSERCA </ci>
          <ci> JIPR </ci>
        </apply>
      </apply>
    </math>
  </component>

  <component cmeta:id="CMT" name="CMT">
    <rdf:RDF xmlns:rdf="http://www.w3.org/1999/02/22-rdf-syntax-ns#">
      <rdf:Description rdf:about="CMT">
        <dc:title>CMT</dc:title>
        <dcterms:alternative>calcium concentration in the mitochondria</dcterms:alternative>  
      </rdf:Description>
    </rdf:RDF>  
    <variable units="micromolar" public_interface="out" name="CMT" initial_value="0.220"/>
    
    <variable units="dimensionless" name="fm"/>
    <variable units="micromolar" name="Km" initial_value="0.01"/>      
    <variable units="micromolar" name="Bm" initial_value="100.0"/>
    
    <variable units="flux" public_interface="in" name="JMCU"/>
    <variable units="flux" public_interface="in" name="JNCX"/>
    <variable units="second" public_interface="in" name="time"/>
    
    <math xmlns="http://www.w3.org/1998/Math/MathML">
      <apply>
        <eq/> 
        <apply>
          <diff/> 
          <bvar>
            <ci>time</ci>
          </bvar> 
          <ci> CMT </ci> 
        </apply>
        <apply>
          <times/>
          <ci> fm </ci>
          <apply>
            <minus/>
            <ci> JMCU </ci>
            <ci> JNCX </ci>
          </apply>
        </apply>
      </apply>

      <apply>
        <eq/>
        <ci> fm </ci>
        <apply>
          <divide/>
          <cn cellml:units="dimensionless"> 1.0 </cn>
          <apply>
            <plus/>
            <cn cellml:units="dimensionless"> 1.0 </cn>
            <apply>
              <divide/>
              <apply>
                <times/>
                <ci> Km </ci>
                <ci> Bm </ci>
              </apply>
              <apply>
                <power/>
                <apply>
                  <plus/>
                  <ci> Km </ci>
                  <ci> CMT </ci>
                </apply>
                <cn cellml:units="dimensionless"> 2.0 </cn>
              </apply>
            </apply>
          </apply>
        </apply>
      </apply>
    </math>
  </component>

  <component cmeta:id="NS1" name="NS1">
    <rdf:RDF xmlns:rdf="http://www.w3.org/1999/02/22-rdf-syntax-ns#">
      <rdf:Description rdf:about="NS1">
        <dc:title>NS1</dc:title>
        <dcterms:alternative>sodium concentration in cytoplasmic subspace 1</dcterms:alternative>  
      </rdf:Description>
    </rdf:RDF>  
    <variable units="micromolar" public_interface="out" name="NS1" initial_value="1.01E4"/>
    
    <variable units="micromolar_coulomb" public_interface="in" name="delta_s"/>
    <variable units="picoampere" public_interface="in" name="I_iNa"/>
    <variable units="second" public_interface="in" name="time"/>
    
    <math xmlns="http://www.w3.org/1998/Math/MathML">
      <apply>
        <eq/> 
        <apply>
          <diff/> 
          <bvar>
            <ci>time</ci>
          </bvar> 
          <ci> NS1 </ci> 
        </apply>
        <apply>
          <times/>
          <apply>
            <minus/>
            <apply>
              <divide/>
              <ci> delta_s </ci>
              <cn cellml:units="dimensionless"> 1.0 </cn>
            </apply>
          </apply>
          <ci> I_iNa </ci>
        </apply>
      </apply>
    </math>
  </component>

  <component name="model_parameters">
    <variable units="attojoule_per_zeptomole_kelvin" public_interface="out" name="R" initial_value="8.314E-3"/> 
    <variable units="femtocoulomb_per_zeptomole" public_interface="out" name="F" initial_value="0.09649"/>
    <variable units="kelvin" public_interface="out" name="T" initial_value="310.16"/>
    <variable units="micromolar" public_interface="out" name="CO" initial_value="1.8E3"/>
    <variable units="micromolar" public_interface="out" name="P" initial_value="1.0"/>
    <variable units="micromolar_coulomb" public_interface="out" name="delta_s" initial_value="26.0"/>
    <variable units="dimensionless" public_interface="out" name="gamma_S1" initial_value="100.0"/>
    <variable units="dimensionless" public_interface="out" name="gamma_S2" initial_value="1.0"/>
    <variable units="dimensionless" public_interface="out" name="gamma_MT" initial_value="200.0"/>
    <variable units="dimensionless" public_interface="out" name="gamma_ER" initial_value="20.0"/>
    <variable units="micromolar" public_interface="out" name="KNSCC" initial_value="0.12"/>
    <variable units="millivolt" public_interface="out" name="ENSCC" initial_value="0.0"/>
    <variable units="dimensionless" public_interface="out" name="hNSCC" initial_value="3.0"/>
  </component>

 
  <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="CS1"/>
    <map_variables variable_2="time" variable_1="time"/>
  </connection>

  <connection>
    <map_components component_2="environment" component_1="CS2"/>
    <map_variables variable_2="time" variable_1="time"/>
  </connection>

  <connection>
    <map_components component_2="environment" component_1="CER"/>
    <map_variables variable_2="time" variable_1="time"/>
  </connection>
  
  <connection>
    <map_components component_2="environment" component_1="CMT"/>
    <map_variables variable_2="time" variable_1="time"/>
  </connection>
  
  <connection>
    <map_components component_2="environment" component_1="NS1"/>
    <map_variables variable_2="time" variable_1="time"/>
  </connection>

  <connection>
    <map_components component_2="environment" component_1="JIPR"/>
    <map_variables variable_2="time" variable_1="time"/>
  </connection> 

  <connection>
    <map_components component_2="CS1" component_1="membrane"/>
    <map_variables variable_2="I_iCa" variable_1="I_iCa"/>
  </connection>

  <connection>
    <map_components component_2="NS1" component_1="membrane"/>
    <map_variables variable_2="I_iNa" variable_1="I_iNa"/>
  </connection>

  <connection>
    <map_components component_2="CS1" component_1="JS1S2"/>
    <map_variables variable_2="CS1" variable_1="CS1"/>
    <map_variables variable_2="JS1S2" variable_1="JS1S2"/>
  </connection>

  <connection>
    <map_components component_2="CS1" component_1="JSERCA"/>
    <map_variables variable_2="CS1" variable_1="CS1"/>
    <map_variables variable_2="JSERCA" variable_1="JSERCA"/>
  </connection>

  <connection>
    <map_components component_2="CS1" component_1="JNCX"/>
    <map_variables variable_2="JNCX" variable_1="JNCX"/>
  </connection>

  <connection>
    <map_components component_2="CS1" component_1="I_PM"/>
    <map_variables variable_2="CS1" variable_1="CS1"/>
  </connection>

  <connection>
    <map_components component_2="CS1" component_1="I_NSCC_Ca"/>
    <map_variables variable_2="CS1" variable_1="CS1"/>
  </connection>

  <connection>
    <map_components component_2="CS1" component_1="I_NSCC_Na"/>
    <map_variables variable_2="CS1" variable_1="CS1"/>
  </connection>

  <connection>
    <map_components component_2="CS1" component_1="model_parameters"/>
    <map_variables variable_2="delta_s" variable_1="delta_s"/>
    <map_variables variable_2="gamma_MT" variable_1="gamma_MT"/>
    <map_variables variable_2="gamma_S1" variable_1="gamma_S1"/>
    <map_variables variable_2="gamma_ER" variable_1="gamma_ER"/>
  </connection>

  <connection>
    <map_components component_2="CS2" component_1="JS1S2"/>
    <map_variables variable_2="CS2" variable_1="CS2"/>
    <map_variables variable_2="JS1S2" variable_1="JS1S2"/>
  </connection>

  <connection>
    <map_components component_2="CS2" component_1="JMCU"/>
    <map_variables variable_2="CS2" variable_1="CS2"/>
    <map_variables variable_2="JMCU" variable_1="JMCU"/>
  </connection>

  <connection>
    <map_components component_2="CS2" component_1="JIPR"/>
    <map_variables variable_2="CS2" variable_1="CS2"/>
    <map_variables variable_2="JIPR" variable_1="JIPR"/>
  </connection>
  
  <connection>
    <map_components component_2="model_parameters" component_1="JIPR"/>
    <map_variables variable_2="P" variable_1="P"/>
  </connection>

  <connection>
    <map_components component_2="CS2" component_1="model_parameters"/>
    <map_variables variable_2="gamma_MT" variable_1="gamma_MT"/>
    <map_variables variable_2="gamma_S1" variable_1="gamma_S1"/>
    <map_variables variable_2="gamma_S2" variable_1="gamma_S2"/>
    <map_variables variable_2="gamma_ER" variable_1="gamma_ER"/>
  </connection>

   <connection>
    <map_components component_2="CER" component_1="JSERCA"/>
    <map_variables variable_2="CER" variable_1="CER"/>
    <map_variables variable_2="JSERCA" variable_1="JSERCA"/>
  </connection>

  <connection>
    <map_components component_2="CER" component_1="JIPR"/>
    <map_variables variable_2="CER" variable_1="CER"/>
    <map_variables variable_2="JIPR" variable_1="JIPR"/>
  </connection>

  <connection>
    <map_components component_2="CMT" component_1="JNCX"/>
    <map_variables variable_2="CMT" variable_1="CMT"/>
    <map_variables variable_2="JNCX" variable_1="JNCX"/>
  </connection>
  
  <connection>
    <map_components component_2="CMT" component_1="JMCU"/>
    <map_variables variable_2="CMT" variable_1="CMT"/>
    <map_variables variable_2="JMCU" variable_1="JMCU"/>
  </connection>

  <connection>
    <map_components component_2="NS1" component_1="model_parameters"/>
    <map_variables variable_2="delta_s" variable_1="delta_s"/>
  </connection>

  <connection>
    <map_components component_2="I_Ca" component_1="membrane"/>
    <map_variables variable_2="I_Ca" variable_1="I_Ca"/>
    <map_variables variable_2="Vm" variable_1="Vm"/>
  </connection>

  <connection>
    <map_components component_2="I_PM" component_1="membrane"/>
    <map_variables variable_2="I_PM" variable_1="I_PM"/>
  </connection>

  <connection>
    <map_components component_2="I_NSCC_Ca" component_1="membrane"/>
    <map_variables variable_2="I_NSCC_Ca" variable_1="I_NSCC_Ca"/>
    <map_variables variable_2="Vm" variable_1="Vm"/>
  </connection>
  
  <connection>
    <map_components component_2="I_NSCC_Ca" component_1="model_parameters"/>
    <map_variables variable_2="hNSCC" variable_1="hNSCC"/>
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