Location: Colegrove, Albrecht, Friel, 2000 @ 0f37af227239 / colegrove_albrecht_friel_2000.cellml

Author:
pmr2.import <nobody@models.cellml.org>
Date:
2006-07-09 07:23:18+12:00
Desc:
committing version01 of colegrove_albrecht_friel_2000
Permanent Source URI:
https://models.cellml.org/workspace/colegrove_albrecht_friel_2000/rawfile/0f37af227239abd09452764782ad468abb75d5c5/colegrove_albrecht_friel_2000.cellml

<?xml version='1.0' encoding='utf-8'?>
<!--  FILE :  colegrove_model_2000.xml

CREATED :  21st March 2002

LAST MODIFIED : 9th April 2003

AUTHOR :  Catherine Lloyd
          Bioengineering Institute
          The University of Auckland
          
MODEL STATUS :  This model conforms to the CellML 1.0 Specification released on
10th August 2001, and the 16/1/02 CellML Metadata 1.0 Specification.

DESCRIPTION :  This file contains a CellML description of Colegrove et al's
2000 model of mitochondrial Ca2+ uptake and release pathways in sympathetic neurons.

CHANGES:  
  18/07/2002 - CML - Added more metadata.
  28/03/2003 - AAC - Changed the name and cmeta:id of the model to reflect the 
                     proper spelling of Colegrove.
  09/04/2003 - AAC - Added publication date information.  
--><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="colegrove_albrecht_friel_2000_version01" name="colegrove_albrecht_friel_2000_version01">
<documentation xmlns="http://cellml.org/tmp-documentation">
<article>
  <articleinfo>
  <title>Quantitative Analysis Of Mitochondrial Ca2+ Uptake And Release Pathways In Sympathetic Neurons</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>
One of the central goals in the study of calcium signalling is to understand the basis of [Ca<superscript>2+</superscript>] dynamics.  This is complicated by the fact that Ca<superscript>2+</superscript> is present in several membrane-bound intracellular compartments, each of which uses a distinct Ca<superscript>2+</superscript> transport system and the rate of Ca<superscript>2+</superscript> transport between these compartments can exhibit a complex non-linear dependence on free [Ca<superscript>2+</superscript>].
</para>

<para>
In their 2000 model, Stephen L. Colegrove, Meredith A. Albrecht and David D. Friel have studied how mitochondrial Ca<superscript>2+</superscript> transport contributes to the redistribution of intracellular Ca<superscript>2+</superscript> during and after depolarisation-evoked Ca<superscript>2+</superscript> entry in sympathetic neurons.  The total Ca<superscript>2+</superscript> flux during the recovery phase following membrane depolarisation was divided into three components (see <xref linkend="fig_cell_diagram"/> below): one representing net Ca<superscript>2+</superscript> extrusion across the plasma membrane (J<subscript>extru</subscript>), one representing mitochondrial Ca<superscript>2+</superscript> uptake via the uniporter (J<subscript>uni</subscript>) and one representing mitochondrial Ca<superscript>2+</superscript> release via the Na<superscript>+</superscript>/Ca<superscript>2+</superscript> exchanger (J<subscript>NaCa</subscript>).  This mathematical model has been translated into a CellML description which can be downloaded in various formats as described in <xref linkend="sec_download_this_model"/>.
</para>

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

<para>
<ulink url="http://www.jgp.org/cgi/content/abstract/115/3/371">Quantitative Analysis of Mitochondrial Ca<superscript>2+</superscript> Uptake and Release Pathways in Sympathetic Neurons  <emphasis>Reconstruction of the Recovery after Depolarisation-evoked [Ca<superscript>2+</superscript>] Elevations</emphasis>
          </ulink>, Stephen L. Colegrove, Meredith A. Albrecht and David D. Friel, 2000, <ulink url="http://www.jgp.org/">
            <emphasis>The Journal Of General Physiology</emphasis>
          </ulink>, 115, 371-388.  (<ulink url="http://www.jgp.org/cgi/content/full/115/3/371">Full text</ulink> and <ulink url="http://www.jgp.org/cgi/reprint/115/3/371.pdf">PDF</ulink> versions of the article are available for Journal Members on the JGP website.)  <ulink url="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&amp;db=PubMed&amp;list_uids=10694264&amp;dopt=Abstract">PubMed ID: 10694264</ulink>  
</para>


<informalfigure float="0" id="fig_cell_diagram">
<mediaobject>
  <imageobject>
    <objectinfo>
      <title>cell schematic for the model</title>
    </objectinfo>
    <imagedata fileref="colegrove_2000.png"/>
  </imageobject>
</mediaobject>
<caption>Schematic of the model indicating Ca<superscript>2+</superscript> compartmentalization in the extracellular matrix, cytosol and the mitochondrial matrix and pathways for Ca<superscript>2+</superscript> ion movement between the compartments.</caption>
</informalfigure>

</sect1>
</article>
</documentation>
  
  
  <!--
    Below, we define some additional units for association with variables and
    constants within the model. The identifiers are fairly self-explanatory.
  -->
  
  <units name="per_second">
    <unit units="second" exponent="-1"/>
  </units>
  
  <units name="millivolt">
    <unit units="volt" prefix="milli"/>
  </units>
  
  <units name="micromolar">
    <unit units="mole" prefix="micro"/>
    <unit units="litre" exponent="-1"/>
  </units>
  
  <units name="nanomolar">
    <unit units="mole" prefix="nano"/>
    <unit units="litre" exponent="-1"/>
  </units>
  
  <units name="nanomolar_per_second">
    <unit units="nanomolar"/>
    <unit units="second" exponent="-1"/>
  </units>
  
  <units name="micromolar_per_second">
    <unit units="micromolar"/>
    <unit units="second" exponent="-1"/>
  </units>
  
  <units name="micro_litre">
    <unit units="litre" prefix="micro"/>
  </units>
  
  <!--
    The "environment" component is used to declare variables that are used by
    all or most of the other components, in this case just "time".
  -->
  <component name="environment">
    <variable units="second" public_interface="out" name="time"/>
  </component>
  
  <component name="Ca_extrusion_across_the_plasma_membrane">
    <variable units="nanomolar_per_second" public_interface="out" name="J_pm"/>
   
    <variable units="nanomolar_per_second" name="J_leak"/>
    <variable units="nanomolar_per_second" name="J_extru"/>
    <variable units="per_second" name="k_leak" initial_value="0.00000037"/>
    <variable units="nanomolar_per_second" name="Vmax_extru" initial_value="28.3"/>
    <variable units="nanomolar" name="EC50_extru" initial_value="378.8"/>
    <variable units="dimensionless" name="n_extru" initial_value="1.8"/>
    <variable units="nanomolar" name="Ca_o" initial_value="0.002"/>
   
    <variable units="nanomolar" public_interface="in" name="Ca_i"/>
    <variable units="second" public_interface="in" name="time"/>
    
    <math xmlns="http://www.w3.org/1998/Math/MathML">
      <apply id="J_pm_calculation">
        <eq/>
        <ci> J_pm </ci>
        <apply>
          <plus/>
          <ci> J_leak </ci>
          <ci> J_extru </ci>
        </apply>
      </apply>
      
      <apply id="J_leak_calculation">
        <eq/>
        <ci> J_leak </ci>
        <apply>
          <times/>
          <ci> k_leak </ci>
          <apply>
            <minus/>
            <ci> Ca_i </ci>
            <ci> Ca_o </ci>
          </apply>
        </apply>
      </apply>
        
      <apply id="J_extru_calculation">
        <eq/>
        <ci> J_extru </ci>
        <apply>
          <divide/>
          <ci> Vmax_extru </ci>
          <apply>
            <plus/>
            <cn cellml:units="dimensionless"> 1.0 </cn>
            <apply>
              <power/>
              <apply>
                <divide/>
                <ci> EC50_extru </ci>
                <ci> Ca_i </ci>
              </apply>
              <ci> n_extru </ci>
            </apply>
          </apply>
        </apply>
      </apply>
    </math>
  </component>
        
  <component name="mitochondrial_Ca_uptake">
    <variable units="nanomolar_per_second" public_interface="out" name="J_uni"/>
   
    <variable units="per_second" name="kuni_max" initial_value="75.9"/>
    <variable units="micromolar" name="EC50_uni" initial_value="10.0"/>
    <variable units="dimensionless" name="n_uni" initial_value="2.0"/>
   
    <variable units="nanomolar" public_interface="in" name="Ca_i"/>
    <variable units="second" public_interface="in" name="time"/>
    
    <math xmlns="http://www.w3.org/1998/Math/MathML">
      <apply id="J_uni_calculation">
        <eq/>
        <ci> J_uni </ci>
        <apply>
          <divide/>
          <apply>
            <times/>
            <ci> kuni_max </ci>
            <ci> Ca_i </ci>
          </apply>
          <apply>
            <plus/>
            <cn cellml:units="dimensionless"> 1.0 </cn>
            <apply>
              <power/>
              <apply>
                <divide/>
                <ci> EC50_uni </ci>
                <ci> Ca_i </ci>
              </apply>
              <ci> n_uni </ci>
            </apply>
          </apply>
        </apply>
      </apply>
    </math>
  </component>
  
  <component name="mitochondrial_Ca_release">
    <variable units="nanomolar_per_second" public_interface="out" name="J_NaCa"/>
    <variable units="nanomolar_per_second" public_interface="out" name="Ca_inhibited_J_NaCa"/>
    <variable units="nanomolar_per_second" public_interface="out" name="J_mito"/>
   
    <variable units="nanomolar_per_second" name="Vmax_NaCa" initial_value="-35.0"/>
    <variable units="nanomolar" name="EC50_NaCa" initial_value="307.0"/>
    <variable units="dimensionless" name="n_inhib" initial_value="6.0"/>
    <variable units="nanomolar" name="k_inhib" initial_value="500.0"/>
    <variable units="dimensionless" name="delta_Ca_i"/>
   
    <variable units="nanomolar_per_second" public_interface="in" name="J_uni"/>
    <variable units="nanomolar" public_interface="in" name="Ca_i"/>
    <variable units="nanomolar" public_interface="in" name="Ca_m"/>
    <variable units="second" public_interface="in" name="time"/>
    
    <math xmlns="http://www.w3.org/1998/Math/MathML">
      <apply id="J_NaCa_calculation">
        <eq/>
        <ci> J_NaCa </ci>
        <apply>
          <divide/>
          <apply>
            <minus/>
            <ci> Vmax_NaCa </ci>
          </apply>
          <apply>
            <plus/>
            <cn cellml:units="dimensionless"> 1.0 </cn>
            <apply>
              <divide/>
              <ci> EC50_NaCa </ci>
              <ci> Ca_m </ci>
            </apply>
          </apply>
        </apply>
      </apply>
      
      <apply id="Ca_inhibited_J_NaCa_calculation">
        <eq/>
        <ci> Ca_inhibited_J_NaCa </ci>
        <apply>
          <divide/>
          <apply>
            <minus/>
            <apply>
              <times/>
              <ci> delta_Ca_i </ci>
              <ci> Vmax_NaCa </ci>
            </apply>
          </apply>
          <apply>
            <plus/>
            <cn cellml:units="dimensionless"> 1.0 </cn>
            <apply>
              <divide/>
              <ci> EC50_NaCa </ci>
              <ci> Ca_i </ci>
            </apply>
          </apply>
        </apply>
      </apply>
      
      <apply id="delta_Ca_i_calculation">
        <eq/>
        <ci> delta_Ca_i </ci>
        <apply>
          <minus/>
          <cn cellml:units="dimensionless"> 1.0 </cn>
          <apply>
            <divide/>
            <cn cellml:units="dimensionless"> 1.0 </cn>
            <apply>
              <minus/>
              <cn cellml:units="dimensionless"> 1.0 </cn>
              <apply>
                <power/>
                <apply>
                  <divide/>
                  <ci> k_inhib </ci>
                  <ci> Ca_i </ci>
                </apply>
                <ci> n_inhib </ci>
              </apply>
            </apply>
          </apply>
        </apply>
      </apply>
      
      <apply id="J_mito_calculation">
        <eq/>
        <ci> J_mito </ci>
        <apply>
          <plus/>
          <ci> J_uni </ci>
          <ci> J_NaCa </ci>
        </apply>
      </apply>
    </math>
  </component>
  
  <component name="intracellular_calcium">
    <variable units="nanomolar" public_interface="out" name="Ca_i"/>
   
    <variable units="nanomolar_per_second" public_interface="in" name="J_pm"/>
    <variable units="nanomolar_per_second" public_interface="in" name="J_mito"/>
    <variable units="second" public_interface="in" name="time"/>
    
    <math xmlns="http://www.w3.org/1998/Math/MathML">
      <apply id="Ca_i_diff_eq">
        <eq/>
        <apply>
          <diff/>
          <bvar>
            <ci> time </ci>
          </bvar>
          <ci> Ca_i </ci>
        </apply>
        <apply>
          <minus/>
          <apply>
            <plus/>
            <ci> J_pm </ci>
            <ci> J_mito </ci>
          </apply>
        </apply>
      </apply>
    </math>
  </component>
  
  <component name="mitochondrial_calcium">
    <variable units="nanomolar" public_interface="out" name="Ca_m"/>
    
    <variable units="dimensionless" name="gamma" initial_value="2.0"/>
    <variable units="micro_litre" name="v_m"/>
    <variable units="dimensionless" name="k_m"/>
    <variable units="micro_litre" name="v_i"/>
    <variable units="dimensionless" name="k_i"/>
    
    <variable units="nanomolar_per_second" public_interface="in" name="J_mito"/>
    <variable units="second" public_interface="in" name="time"/>
    
    <math xmlns="http://www.w3.org/1998/Math/MathML">
      <apply id="Ca_m_diff_eq">
        <eq/>
        <apply>
          <diff/>
          <bvar>
            <ci> time </ci>
          </bvar>
          <ci> Ca_m </ci>
        </apply>
        <apply>
          <divide/>
          <ci> J_mito </ci>
          <ci> gamma </ci>
        </apply>
      </apply>
      
      <apply id="gamma_calculation">
        <eq/>
        <ci> gamma </ci>
        <apply>
          <divide/>
          <apply>
            <times/>
            <ci> v_m </ci>
            <ci> k_m </ci>
          </apply>
          <apply>
            <times/>
            <ci> v_i </ci>
            <ci> k_i </ci>
          </apply>
        </apply>
      </apply>
    </math>
  </component>
  
  <connection>
    <map_components component_2="environment" component_1="Ca_extrusion_across_the_plasma_membrane"/>
    <map_variables variable_2="time" variable_1="time"/>
  </connection>
  
  <connection>
    <map_components component_2="environment" component_1="mitochondrial_Ca_uptake"/>
    <map_variables variable_2="time" variable_1="time"/>
  </connection>
  
  <connection>
    <map_components component_2="environment" component_1="mitochondrial_Ca_release"/>
    <map_variables variable_2="time" variable_1="time"/>
  </connection>
  
  <connection>
    <map_components component_2="environment" component_1="intracellular_calcium"/>
    <map_variables variable_2="time" variable_1="time"/>
  </connection>
  
  <connection>
    <map_components component_2="environment" component_1="mitochondrial_calcium"/>
    <map_variables variable_2="time" variable_1="time"/>
  </connection> 
  
  <connection>
    <map_components component_2="intracellular_calcium" component_1="Ca_extrusion_across_the_plasma_membrane"/>
    <map_variables variable_2="J_pm" variable_1="J_pm"/>
    <map_variables variable_2="Ca_i" variable_1="Ca_i"/>
  </connection>
  
  <connection>
    <map_components component_2="intracellular_calcium" component_1="mitochondrial_Ca_uptake"/>
    <map_variables variable_2="Ca_i" variable_1="Ca_i"/>
  </connection>
  
  <connection>
    <map_components component_2="mitochondrial_Ca_release" component_1="mitochondrial_Ca_uptake"/>
    <map_variables variable_2="J_uni" variable_1="J_uni"/>
  </connection>
  
  <connection>
    <map_components component_2="intracellular_calcium" component_1="mitochondrial_Ca_release"/>
    <map_variables variable_2="J_mito" variable_1="J_mito"/>
    <map_variables variable_2="Ca_i" variable_1="Ca_i"/>
  </connection>
  
  <connection>
    <map_components component_2="mitochondrial_calcium" component_1="mitochondrial_Ca_release"/>
    <map_variables variable_2="Ca_m" variable_1="Ca_m"/>
    <map_variables variable_2="J_mito" variable_1="J_mito"/>
  </connection>
  

<rdf:RDF>
  <rdf:Bag rdf:about="rdf:#c32af19e-6bc0-4535-b0e3-d355cba81348">
    <rdf:li>calcium dynamics</rdf:li>
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  <rdf:Description rdf:about="rdf:#349b78ad-3f02-4edf-9190-19487e3cba3b">
    <vCard:Given>Stephen</vCard:Given>
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          This is the CellML description of Colegrove et al's 2000 model of 
          mitochondrial Ca2+ uptake and release pathways in sympathetic neurons.
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    <dcterms:W3CDTF>2003-04-09</dcterms:W3CDTF>
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  <rdf:Description rdf:about="rdf:#945a3eb9-01d9-4da2-b658-976b365bccd9">
    <vCard:Given>Catherine</vCard:Given>
    <vCard:Family>Lloyd</vCard:Family>
    <vCard:Other>May</vCard:Other>
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    <dcterms:modified rdf:resource="rdf:#bf0bc8c5-41da-41a8-9215-4b2d40657a05"/>
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          Changed the name and cmeta:id of the model to reflect the proper 
          spelling of Colegrove.
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  <rdf:Description rdf:about="rdf:#b8fb32d7-5689-4947-8dc3-04edfa9ffe04">
    <vCard:Given>Meredith</vCard:Given>
    <vCard:Family>Albrecht</vCard:Family>
    <vCard:Other>A</vCard:Other>
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  <rdf:Description rdf:about="rdf:#55703b79-c4e1-4484-89dd-90f1593dfdae">
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    <dc:creator rdf:resource="rdf:#9a684b74-16af-46ac-9e9b-d88c51828e2f"/>
    <dc:title>
            Quantitive Analysis of Mitochondrial Ca2+ Uptake and Release                     Pathways in Sympathetic Neurons Reconstruction of the Recovery after             Depolarisation-evoked [Ca2+] Elevations
          </dc:title>
    <bqs:volume>115</bqs:volume>
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