Location: Warashina, Ogura, 2004 @ bef0f389168b / warashina_ogura_2004.cellml

Author:
Hanne <Hanne@hanne-nielsens-macbook.local>
Date:
2009-12-15 11:50:17+13:00
Desc:
Added images in ai and svg format, removed non pub med references
Permanent Source URI:
https://models.physiomeproject.org/workspace/warashina_ogura_2004/rawfile/bef0f389168b730b4d9e70c89f5f3b34bb49adb7/warashina_ogura_2004.cellml

<?xml version='1.0' encoding='utf-8'?>
<!-- FILE : warashina_model_2004.xml

CREATED : 3rd February 2004 

LAST MODIFIED : 27th April 2005

AUTHOR : Catherine Lloyd
         Bioengineering Instute
         The University of Auckland
         
MODEL STATUS : This model conforms to the CellML 1.0 Specification released on
10th August 2001, and the 16/01/2002 CellML Metadata 1.0 Specification.

DESCRIPTION : This file contains a CellML description of Warashina and Ogura's 2004 mathematical model of stimulation-secretion coupling in a chromaffin cell.

CHANGES: 
  27/04/2005 - PJV - Made MathML id's unique. Changed unit dimension
                     to correct inconsistancy. Removed undefined
                     initial values.
--><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="warashina_ogura_2004_version01" name="warashina_ogura_2004_version01">
<documentation xmlns="http://cellml.org/tmp-documentation">
<article>
  <articleinfo>
  <title>Modelling Stimulation-Sectretion Coupling in a Chromaffin Cell</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 is the original unchecked version of the model imported from the previous
            CellML model repository, 24-Jan-2006.
          </para>
  </section>
  <sect1 id="sec_structure">
<title>Model Structure</title>

<para>
Adrenal chromaffin cells have been used extensively for studying the mechanisms involved in stimulation-secretion coupling, namely electrophysiological progesses, signal transduction pathways, calcium homeostasis, and exocytotic processes.  However, despite the accululation of large quantities of experimental data, a clear understanding of how these processes interact is lacking.  In the Warashina and Ogura 2004 publication described here, the authors present a mathematical model which describes a chromaffin cell (see the figure below).  This model is able to simulate the cell's secretory responses, including the process of stimulation-secretion coupling.
</para>

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

<para>
Modeling of stimulation-secretion coupling in a chromaffin cell, A. Warashina and T. Ogura, 2004, <emphasis>European Journal of Physiology</emphasis>, 448, 369-391.  <ulink url="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&amp;db=PubMed&amp;list_uids=14730449&amp;dopt=Abstract">PubMed ID: 14730449</ulink> 
</para>

<informalfigure float="0" id="fig_cell_diagram">
<mediaobject>
  <imageobject>
    <objectinfo>
      <title>cell diagram</title>
    </objectinfo>
    <imagedata fileref="warashina_2004.png"/>
  </imageobject>
</mediaobject>
<caption>The model chromaffin cell includes mechanisms involved in the excitatory synapse, Hodgkin-Huxley type Na<superscript>+</superscript> and K<superscript>+</superscript> channels, volatage-dependent Ca<superscript>2+</superscript> channels, Ca<superscript>2+</superscript>-dependent K<superscript>+</superscript> channels, Ca<superscript>2+</superscript> extrusion, buffered diffusion of intracellular Ca<superscript>2+</superscript>, Ca<superscript>2+</superscript> indication with a fluorescent dye, and Ca<superscript>2+</superscript>-triggered secretion.</caption>
</informalfigure>

<para>
Model simulations were carried out using the <ulink url="http://www.neuron.yale.edu/">NEURON</ulink> simulation environment.  The simulations were able to reproduce several of the experimental results reported in the literature.
</para>

</sect1>
</article>
</documentation>
  
  
  
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                  <apply>
                    <times/>
                    <cn cellml:units="dimensionless"> 2.0 </cn>
                    <ci> V </ci>
                    <ci> F </ci>
                  </apply>
                  <apply>
                    <times/>
                    <ci> R </ci>
                    <ci> T </ci>
                  </apply>
                </apply>
              </apply>
            </apply>
          </apply>
        </apply>
      </apply>
    </math>
  </component>
  
  <component name="calcium_channel_m_gate">
    <variable units="dimensionless" public_interface="out" name="m"/>
    
    <variable units="per_millisecond" name="alpha_m"/>
    <variable units="per_millisecond" name="beta_m"/>
    
    <variable units="millivolt" public_interface="in" name="V"/>
    <variable units="millisecond" public_interface="in" name="time"/>
   
    <math xmlns="http://www.w3.org/1998/Math/MathML">
      <apply id="calcium_channel_m_gate_alpha_m_calculation">
        <eq/>
        <ci> alpha_m </ci>
        <apply>
          <divide/>
          <cn cellml:units="per_millisecond"> 5.0 </cn>
          <apply>
            <plus/>
            <cn cellml:units="dimensionless"> 1.0 </cn>
            <apply>
              <exp/>
              <apply>
                <times/>
                <cn cellml:units="dimensionless"> -0.075 </cn>
                <apply>
                  <minus/>
                  <ci> V </ci> 
                  <cn cellml:units="millivolt"> 5.0 </cn>
                </apply>
              </apply>
            </apply>
          </apply>
        </apply>
      </apply>
      
      <apply id="calcium_channel_m_gate_beta_m_calculation">
        <eq/>
        <ci> beta_m </ci>
        <apply>
          <divide/>
          <apply>
            <times/>
            <cn cellml:units="per_millisecond"> 0.05 </cn>
            <apply>
              <minus/>
              <ci> V </ci>
              <cn cellml:units="millivolt"> 2.0 </cn>
            </apply>
          </apply>
          <apply>
            <minus/>
            <cn cellml:units="dimensionless"> 1.0 </cn>
            <apply>
              <exp/>
              <apply>
                <divide/>
                <apply>
                  <minus/>
                  <ci> V </ci> 
                  <cn cellml:units="millivolt"> 2.0 </cn>
                </apply>
                <cn cellml:units="millivolt"> 8.0 </cn>
              </apply>
            </apply>
          </apply>
        </apply>
      </apply>
      
      <apply id="calcium_channel_m_gate_dm_dt">
        <eq/>
        <apply>
          <diff/>
          <bvar>
            <ci> time </ci>
          </bvar>
          <ci> m </ci>
        </apply>
        <apply>
          <minus/>
          <apply>
            <times/>
            <ci> alpha_m </ci>
            <apply>
              <minus/>
              <cn cellml:units="dimensionless"> 1.0 </cn>
              <ci> m </ci>
            </apply>
          </apply>
          <apply>
            <times/>
            <ci> beta_m </ci>
            <ci> m </ci>
          </apply>
        </apply>
      </apply>
    </math>
  </component>
  
  <component name="calcium_channel_h_gate">
    <variable units="dimensionless" public_interface="out" name="h"/>
    
    <variable units="dimensionless" name="Fr"/>
    <variable units="dimensionless" name="Ff" initial_value="0.79"/>
    <variable units="dimensionless" name="Fm" initial_value="0.0"/>
    <variable units="dimensionless" name="Fs" initial_value="0.0"/>
    <variable units="millisecond" name="tau_f" initial_value="500.0"/>
    <variable units="millisecond" name="tau_m"/>
    <variable units="millisecond" name="tau_s"/>
    
    <variable units="millisecond" public_interface="in" name="time"/>
   
    <math xmlns="http://www.w3.org/1998/Math/MathML">
      <apply id="h_calculation">
        <eq/>
        <ci> h </ci>
        <apply>
          <plus/>
          <apply>
            <times/>
            <ci> Ff </ci>
            <apply>
              <exp/>
              <apply>
                <divide/>
                <apply>
                  <minus/> 
                  <ci> time </ci>
                </apply>
                <ci> tau_f </ci> 
              </apply>
            </apply>
          </apply>
          <apply>
            <times/>
            <ci> Fm </ci>
            <apply>
              <exp/>
              <apply>
                <divide/>
                <apply>
                  <minus/> 
                  <ci> time </ci>
                </apply>
                <ci> tau_m </ci> 
              </apply>
            </apply>
          </apply>
          <apply>
            <times/>
            <ci> Fs </ci>
            <apply>
              <exp/>
              <apply>
                <divide/>
                <apply>
                  <minus/> 
                  <ci> time </ci>
                </apply>
                <ci> tau_s </ci> 
              </apply>
            </apply>
          </apply>
          <ci> Fr </ci>
        </apply>
      </apply>
    </math>
  </component>
  
  <component name="calcium_dependent_potassium_channel">
    <variable units="microA_per_cm2" public_interface="out" name="i_SK"/>

    <variable units="milliS_per_cm2" name="g_SK" initial_value="3.0"/>
    
    <variable units="millisecond" 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="Ca0"/>
    <variable units="millivolt" public_interface="in" name="E_K"/>
    
    <variable units="dimensionless" private_interface="in" name="m"/>
    
    <math xmlns="http://www.w3.org/1998/Math/MathML">
      <apply id="i_SK_calculation">
        <eq/>
        <ci> i_SK </ci>
        <apply>
          <times/>
          <ci> g_SK </ci>
          <apply>
            <power/>
            <ci> m </ci>
            <cn cellml:units="dimensionless"> 2.0 </cn>
          </apply>
          <apply>
            <minus/>
            <ci> V </ci>
            <ci> E_K </ci>
          </apply>
        </apply>
      </apply>
    </math>
  </component>
  
  <component name="calcium_dependent_potassium_channel_m_gate">
    <variable units="dimensionless" public_interface="out" name="m"/>
    
    <variable units="dimensionless" name="m_infinity"/>
    <variable units="metre_per_second" name="beta_k" initial_value="0.1"/>
    <variable units="dimensionless" name="n_SK" initial_value="1.7"/>
    <variable units="millisecond" name="tau_m"/>
    <variable units="millimolar" name="Car"/>
    <variable units="nanomolar" name="Cac" initial_value="700.0"/>
    
    <variable units="millimolar" public_interface="in" name="Ca0"/>
    <variable units="millisecond" public_interface="in" name="time"/>
   
    <math xmlns="http://www.w3.org/1998/Math/MathML">
      <apply id="m_infinity_calculation">
        <eq/>
        <ci> m_infinity </ci>
        <apply>
          <divide/>
          <ci> Car </ci>
          <apply>
            <plus/>
            <cn cellml:units="dimensionless"> 1.0 </cn>
            <ci> Car </ci>
          </apply>
        </apply>
      </apply>
      
      <apply id="tau_m_calculation">
        <eq/>
        <ci> tau_m </ci>
        <apply>
          <divide/>
          <cn cellml:units="millisecond"> 1.0 </cn>
          <apply>
            <times/>
            <ci> beta_k </ci>
            <apply>
              <plus/>
              <cn cellml:units="millimolar"> 1.0 </cn>
              <ci> Car </ci>
            </apply>
          </apply>
        </apply>
      </apply>
      
      <apply id="Car_calculation">
        <eq/>
        <ci> Car </ci>
        <apply>
          <power/>
          <apply>
            <divide/>
            <ci> Ca0 </ci>
            <ci> Cac </ci> 
          </apply>
          <ci> n_SK </ci> 
        </apply>
      </apply>
      
      <apply id="calcium_dependent_potassium_channel_m_gate_dm_dt">
        <eq/>
        <apply>
          <diff/>
          <bvar>
            <ci> time </ci>
          </bvar>
          <ci> m </ci>
        </apply>
        <apply>
          <divide/>
          <apply>
            <minus/>
            <apply>
              <minus/>
              <ci> m </ci>
              <ci> m_infinity </ci>
            </apply>
          </apply>
          <ci> tau_m </ci>
        </apply>
      </apply>
    </math>
  </component>
  
  <component name="buffered_calcium_diffusion">
    <variable units="millimolar" public_interface="out" name="Bu"/>
    <variable units="millimolar" public_interface="out" name="CaBu"/>
    <variable units="per_millimolar_per_millisecond" public_interface="out" name="k1b" initial_value="100.0"/>
    <variable units="per_millisecond" public_interface="out" name="k2b" initial_value="10.0"/>
    <variable units="per_millisecond" public_interface="out" name="kfc"/>
    <variable units="per_millisecond" public_interface="out" name="kbc"/>
    
    <variable units="millimolar" name="Cai"/>
    <variable units="millimolar" name="Cai2"/>
    <variable units="micrometre2_per_millisecond" name="DCa" initial_value="0.22"/>
    <variable units="micromolar_per_millisecond" name="FCai"/>
    <variable units="millimolar" name="TBu" initial_value="4.0"/>
    
    <variable units="micrometre" public_interface="in" name="delta_r"/>
    <variable units="micrometre2" public_interface="in" name="Ai2"/>
    <variable units="micrometre3" public_interface="in" name="vol_i"/>
     
    <math xmlns="http://www.w3.org/1998/Math/MathML">
      <apply id="Cai_calculation">
        <eq/>
        <ci> Cai </ci>
        <apply>
          <minus/>
          <apply>
            <times/>
            <ci> CaBu </ci>
            <ci> k2b </ci>
          </apply>
          <apply>
            <times/>
            <ci> Cai </ci>
            <ci> Bu </ci>
            <ci> k1b </ci>
          </apply> 
        </apply>
      </apply>
      
      <apply id="Bu_calculation">
        <eq/>
        <ci> Bu </ci>
        <apply>
          <minus/>
          <apply>
            <times/>
            <ci> CaBu </ci>
            <ci> k2b </ci>
          </apply>
          <apply>
            <times/>
            <ci> Cai </ci>
            <ci> Bu </ci>
            <ci> k1b </ci>
          </apply> 
        </apply>
      </apply>
      
      <apply id="CaBu_calculation">
        <eq/>
        <ci> CaBu </ci>
        <apply>
          <minus/>
          <apply>
            <times/>
            <ci> Cai </ci>
            <ci> Bu </ci>
            <ci> k1b </ci>
          </apply>
          <apply>
            <times/>
            <ci> CaBu </ci>
            <ci> k2b </ci>
          </apply>
        </apply>
      </apply>
      
      <apply id="FCai_calculation">
        <eq/>
        <ci> FCai </ci>
        <apply>
          <times/>
          <apply>
            <minus/>
            <ci> Cai2 </ci>
            <ci> Cai </ci>
          </apply>
          <ci> DCa </ci>
          <apply>
            <divide/>
            <ci> Ai2 </ci>
            <ci> delta_r </ci>
          </apply> 
        </apply>
      </apply>
      
      <apply id="kfc_calculation">
        <eq/>
        <ci> kfc </ci>
        <apply>
          <divide/>
          <apply>
            <times/>
            <ci> DCa </ci>
            <ci> Ai2 </ci>
          </apply>
          <apply>
            <times/>
            <ci> delta_r </ci>
            <ci> vol_i </ci>
          </apply> 
        </apply>
      </apply>
      
      <apply id="kbc_calculation">
        <eq/>
        <ci> kbc </ci>
        <apply>
          <divide/>
          <apply>
            <times/>
            <ci> DCa </ci>
            <ci> Ai2 </ci>
          </apply>
          <apply>
            <times/>
            <ci> delta_r </ci>
            <ci> vol_i </ci>
          </apply> 
        </apply>
      </apply>
    </math>
  </component>
  
  <component name="calcium_extrusion">
    <variable units="microA_per_cm2" public_interface="out" name="i_ex"/>
    
    <variable units="microA_per_cm2" name="Vmax" initial_value="3.0"/>
    <variable units="nanomolar" name="Kex" initial_value="830.0"/>
    <variable units="nanomolar" name="Ca_rest" initial_value="100.0"/>
    
    <variable units="millimolar" public_interface="in" name="Ca0"/>
    
    <math xmlns="http://www.w3.org/1998/Math/MathML">
      <apply id="i_ex_calculation">
        <eq/>
        <ci> i_ex </ci>
        <apply>
          <minus/>
          <apply>
            <times/>
            <ci> Vmax </ci>
            <apply>
              <divide/>
              <ci> Ca0 </ci>
              <apply>
                <plus/>
                <ci> Kex </ci>
                <ci> Ca0 </ci>
              </apply>
            </apply>
          </apply>
          <apply>
            <times/>
            <ci> Vmax </ci>
            <apply>
              <divide/>
              <ci> Ca_rest </ci>
              <apply>
                <plus/>
                <ci> Kex </ci>
                <ci> Ca_rest </ci>
              </apply>
            </apply>
          </apply>
        </apply>
      </apply>
    </math>
  </component>
  
  <component name="calcium_triggered_exocytosis">
    <variable units="millimolar_per_millisecond" name="SR"/>
    <variable units="per_millisecond" name="k1f"/>
    <variable units="per_millisecond" name="k1b"/>
    <variable units="per_millisecond" name="k2"/>
    <variable units="per_millisecond" name="a1" initial_value="9.0E-6"/>
    <variable units="per_millisecond" name="a2" initial_value="5.5E-6"/>
    <variable units="per_micromolar3_per_millisecond" name="a3" initial_value="2.3E-5"/>
    <variable units="micromolar" name="b1" initial_value="1.2"/>
    <variable units="dimensionless" name="B"/>
    <variable units="dimensionless" name="A" initial_value="2000.0"/>
    <variable units="dimensionless" name="C"/>
    
    <variable units="millimolar" public_interface="in" name="Ca0"/>
    
    <math xmlns="http://www.w3.org/1998/Math/MathML">
      <apply id="k1f_calculation">
        <eq/>
        <ci> k1f </ci>
        <apply>
          <times/>
          <ci> a1 </ci>
          <apply>
            <divide/>
            <ci> Ca0 </ci>
            <apply>
              <plus/>
              <ci> b1 </ci>
              <ci> Ca0 </ci>
            </apply>
          </apply>
        </apply>
      </apply>
      
      <apply id="k1b_calculation">
        <eq/>
        <ci> k1b </ci>
        <ci> a2 </ci>
      </apply>
      
      <apply id="k2_calculation">
        <eq/>
        <ci> k2 </ci>
        <apply>
          <times/>
          <ci> a3 </ci>
          <apply>
            <power/>
            <ci> Ca0 </ci>
            <cn cellml:units="dimensionless"> 3.0 </cn>
          </apply>
        </apply>
      </apply>
      
      <apply id="B_calculation">
        <eq/>
        <ci> B </ci>
        <apply>
          <minus/>
          <apply>
            <times/>
            <ci> A </ci>
            <ci> k1f </ci>
          </apply>
          <apply>
            <plus/>
            <apply>
              <times/>
              <ci> B </ci>
              <ci> k1b </ci>
            </apply>
            <apply>
              <times/>
              <ci> B </ci>
              <ci> k2 </ci>
            </apply>
          </apply>
        </apply>
      </apply>
      
      <apply id="C_calculation">
        <eq/>
        <ci> C </ci>
        <apply>
          <times/>
          <ci> B </ci>
          <ci> k2 </ci>
        </apply>
      </apply>
      
      <apply id="SR_calculation">
        <eq/>
        <ci> SR </ci>
        <apply>
          <times/>
          <ci> k2 </ci>
          <ci> B </ci>
        </apply>
      </apply>
    </math>
  </component>
  
  <component name="calcium_indicator">
    <variable units="millimolar" public_interface="out" name="CaDy"/>
    <variable units="millimolar" public_interface="out" name="Dy"/>
    <variable units="per_millimolar_per_millisecond" public_interface="out" name="k1d" initial_value="500.0"/>
    <variable units="per_millisecond" public_interface="out" name="k2d"/>
    
    <variable units="millimolar" name="FDy"/>
    <variable units="millimolar" name="Dyi2"/>
    <variable units="millimolar" name="Cai"/>
    <variable units="millimolar" name="FCaDy"/>
    <variable units="micromolar" name="TDy" initial_value="5.0"/>
    <variable units="micrometre2_per_millisecond" name="Ddy" initial_value="0.05"/>
    <variable units="nanomolar" name="Dkd" initial_value="240.0"/>
    <variable units="dimensionless" name="F0" initial_value="0.36"/>
    <variable units="per_millisecond" name="kfd"/>
    <variable units="per_millisecond" name="kbd"/>
    
    <variable units="micrometre" public_interface="in" name="delta_r"/>
    <variable units="micrometre2" public_interface="in" name="Ai2"/>
    <variable units="micrometre3" public_interface="in" name="vol_i"/>
    
    <math xmlns="http://www.w3.org/1998/Math/MathML">
      <apply id="Dy_calculation">
        <eq/>
        <ci> Dy </ci>
        <apply>
          <minus/>
          <apply>
            <times/>
            <ci> Dyi2 </ci>
            <ci> kbd </ci>
          </apply>
          <apply>
            <times/>
            <ci> Dy </ci>
            <ci> kfd </ci>
          </apply>
        </apply>
      </apply>
      
      <apply id="kfd_calculation">
        <eq/>
        <ci> kfd </ci>
        <apply>
          <divide/>
          <apply>
            <times/>
            <ci> Ddy </ci>
            <ci> Ai2 </ci>
          </apply>
          <apply>
            <times/>
            <ci> delta_r </ci>
            <ci> vol_i </ci>
          </apply>
        </apply>
      </apply>
      
      <apply id="kbd_calculation">
        <eq/>
        <ci> kbd </ci>
        <apply>
          <divide/>
          <apply>
            <times/>
            <ci> Ddy </ci>
            <ci> Ai2 </ci>
          </apply>
          <apply>
            <times/>
            <ci> delta_r </ci>
            <ci> vol_i </ci>
          </apply>
        </apply>
      </apply>
      
      <apply id="CaDy_calculation">
        <eq/>
        <ci> CaDy </ci>
        <apply>
          <minus/>
          <apply>
            <times/>
            <ci> Dy </ci>
            <ci> Cai </ci>
            <ci> k1d </ci>
          </apply>
          <apply>
            <times/>
            <ci> CaDy </ci>
            <ci> k2d </ci>
          </apply>
        </apply>
      </apply>
      
      <apply id="FDy_calculation">
        <eq/>
        <ci> FDy </ci>
        <apply>
          <plus/>
          <apply>
            <times/>
            <apply>
              <minus/>
              <cn cellml:units="dimensionless"> 1.0 </cn>
              <ci> F0 </ci>
            </apply>
            <ci> FCaDy </ci>
          </apply>
          <ci> F0 </ci>
        </apply>
      </apply>
    </math>
  </component>
  
  <component name="calcium_concentration">
    <variable units="millimolar" public_interface="out" name="Ca0"/>
              
    <variable units="micrometre2" name="A0"/>
    <variable units="micrometre3" name="vol0"/>
    <variable units="millimolar" name="Ca1"/>
    
    <variable units="millisecond" public_interface="in" name="time"/>
    <variable units="microA_per_cm2" public_interface="in" name="i_Ca"/>
    <variable units="microA_per_cm2" public_interface="in" name="i_ex"/>
    <variable units="millimolar" public_interface="in" name="CaBu"/>
    <variable units="millimolar" public_interface="in" name="Bu"/>
    <variable units="millimolar" public_interface="in" name="CaDy"/>
    <variable units="millimolar" public_interface="in" name="Dy"/>
    <variable units="coulomb_per_mole" public_interface="in" name="F"/>
    <variable units="per_millimolar_per_millisecond" public_interface="in" name="k1d"/>
    <variable units="per_millisecond" public_interface="in" name="k2d"/>
    <variable units="per_millimolar_per_millisecond" public_interface="in" name="k1b"/>
    <variable units="per_millisecond" public_interface="in" name="k2b"/>
    <variable units="per_millisecond" public_interface="in" name="kfc"/>
    <variable units="per_millisecond" public_interface="in" name="kbc"/>
     
    <math xmlns="http://www.w3.org/1998/Math/MathML">
      <apply id="Ca0_diff_eq">
        <eq/>
        <apply>
          <diff/>
          <bvar>
            <ci> time </ci>
          </bvar>
          <ci> Ca0 </ci>
        </apply>
        <apply>
          <minus/>
          <apply>
            <plus/>
            <apply>
              <times/>
              <ci> kbc  </ci>
              <ci> Ca1 </ci>
            </apply>
            <apply>
              <times/>
              <ci> k2b  </ci>
              <ci> CaBu </ci>
            </apply>
            <apply>
              <times/>
              <ci> k2d  </ci>
              <ci> CaDy </ci>
            </apply>
          </apply>
          <apply>
            <plus/>
            <apply>
              <divide/>
              <apply>
                <times/>
                <apply>
                  <plus/>
                  <ci> i_Ca </ci>
                  <ci> i_ex </ci>
                </apply>
                <ci> A0 </ci>
              </apply>
              <apply>
                <times/>
                <cn cellml:units="dimensionless"> 2.0 </cn>
                <ci> F </ci>
                <ci> vol0 </ci>
              </apply>
            </apply>
            <apply>
              <times/>
              <ci> kfc  </ci>
              <ci> Ca0 </ci>
            </apply>
            <apply>
              <times/>
              <ci> k1b  </ci>
              <ci> Bu </ci>
              <ci> Ca0 </ci>
            </apply>
            <apply>
              <times/>
              <ci> k1d  </ci>
              <ci> Dy </ci>
              <ci> Ca0 </ci>
            </apply>
          </apply>
        </apply>
      </apply>
    </math>
  </component>
  
  <component name="model_parameters">
    <variable units="joule_per_mole_kelvin" public_interface="out" name="R" initial_value="8.3144"/>
    <variable units="kelvin" public_interface="out" name="T" initial_value="310.15"/>
    <variable units="coulomb_per_mole" public_interface="out" name="F" initial_value="96485"/>
    <variable units="micrometre" public_interface="out" name="delta_r"/>
    <variable units="micrometre2" public_interface="out" name="Ai2"/>
    <variable units="micrometre3" public_interface="out" name="vol_i"/>
    <variable units="millivolt" public_interface="out" name="E_K" initial_value="-80.0"/>
    
    <variable units="micrometre" name="diameter" initial_value="15.0"/>
    <variable units="dimensionless" name="Nc" initial_value="6.0"/>
    
    <math xmlns="http://www.w3.org/1998/Math/MathML">
      <apply id="delta_r_calculation">
        <eq/>
        <ci> delta_r </ci>
        <apply>
          <divide/>
          <ci> diameter </ci>
          <apply>
            <times/>
            <cn cellml:units="dimensionless"> 2.0 </cn>
            <apply>
              <minus/>
              <ci> Nc </ci>
              <cn cellml:units="dimensionless"> 1.0 </cn>
            </apply>
          </apply> 
        </apply>
      </apply>
    </math>
  </component>
  
  
  <group>
    <relationship_ref relationship="containment"/>
    <component_ref component="membrane">
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