Location: Activation of the Liver Glycogen Phosphorylase by Ca2+ Oscillations: a Theoretical Study @ 2dfd72747a38 / gall_2000.cellml

Author:

dave <dave@bcs.co.nz>

Date:

2013-01-04 12:00:30+13:00

Desc:

'Z' is no longer directly used for dPha/dt, so remove from component.

Permanent Source URI:

https://models.cellml.org/workspace/35d/rawfile/2dfd72747a38b445cf98d2cd094d4bfd391ecc49/gall_2000.cellml

<?xml version="1.0"?>

<!--

This CellML file was generated on 8/18/2011 at 1:13:53 at PM using:



COR (0.9.31.1409)

Copyright 2002-2011 Dr Alan Garny

http://cor.physiol.ox.ac.uk/ - cor@physiol.ox.ac.uk



CellML 1.0 was used to generate this model

http://www.cellml.org/

--><model xmlns="http://www.cellml.org/cellml/1.0#" xmlns:cmeta="http://www.cellml.org/metadata/1.0#" cmeta:id="gall_2000" name="gall_2000">







<documentation xmlns="http://cellml.org/tmp-documentation">

    <article>

      <section id="sec_status">

        <title>Model Status</title>

        <para>

         Made in COR. Model a runs in OpenCell to recreate results from  published paper but model b does not reproduce results. CellML files are based on equations 1-3 (a) and 1 and 4-8 (b).

          </para>

      </section>

      <sect1 id="sec_structure">

        <title>Model Structure</title>

        <para>

ABSTRACT: Cytosolic calcium plays a crucial role as a second messenger in cellular signalling. Various cell types, including hepatocytes, display Ca(2+)oscillations when stimulated by an extracellular signal. However, the biological relevance of this temporal organization remains unclear. In this paper, we investigate theoretically the effect of Ca(2+)oscillations on a particular example of cell regulation: the phosphorylation-dephosphorylation cycle controlling the activation of glycogen phosphorylase in hepatocytes. By modelling periodic sinusoidal variations in the intracellular Ca(2+)concentration, we show that Ca(2+)oscillations reduce the threshold for the activation of the enzyme. Furthermore, as the activation of a given enzyme depends on the kinetics of its phosphorylation-dephosphorylation cycle, specificity can be encoded by the oscillation frequency. Finally, using a model for signal-induced Ca(2+)oscillations based on Ca(2+)-induced Ca(2+)release, we show that realistic Ca(2+)oscillations can potentiate the response to a hormonal stimulation. These results indicate that Ca(2+)oscillations in hepatocytes could contribute to increase the efficiency and specificity of cellular signalling, as shown experimentally for gene expression in lymphocytes (Dolmetsch et al., 1998).</para>



        <para>

The complete original paper reference is cited below:

</para>

        <para>

         Activation of the Liver Glycogen Phosphorylase by Ca2+ Oscillations: a Theoretical Study, David Gall et al, 2009, <emphasis>Activation of the Liver Glycogen Phosphorylase by Ca2+ Oscillations: 

a Theoretical Study </emphasis>, 207, 445-454. <ulink url="http://www.ncbi.nlm.nih.gov/pubmed/11093832">PubMed ID: 11093832</ulink>

        </para>

		

        <informalfigure float="0" id="fig_reaction_diagram">

          <mediaobject>

            <imageobject>

              <objectinfo>

                <title>Image depicting calcium flow in model</title>

              </objectinfo>

              <imagedata fileref="gall_2000.png"/>

            </imageobject>

          </mediaobject>

          <caption>Calcium in cell</caption>

        </informalfigure>

      </sect1>

    </article>

  </documentation>





   <units name="minute">

      <unit multiplier="60" units="second"/>

   </units>

   <units name="per_minute">

      <unit exponent="-1" units="minute"/>

   </units>

   <units name="millimole">

      <unit prefix="milli" units="mole"/>

   </units>

   <units name="micromole">

      <unit prefix="micro" units="mole"/>

   </units>

   <units name="micromolar">

      <unit units="micromole"/>

      <unit exponent="-1" units="litre"/>

   </units>

   <component name="environment">

      <variable cmeta:id="environment_time" name="time" public_interface="out" units="minute"/>

   </component>

   <component name="Pha">

      <variable cmeta:id="Pha_Pha" initial_value="0.098" name="Pha" units="dimensionless"/>

      <variable name="V_1" public_interface="in" units="dimensionless"/>

      <variable name="K_1" public_interface="in" units="dimensionless"/>

      <variable initial_value="0.6" name="V_M2" units="per_minute"/>

      <variable initial_value="9" name="alpha" units="dimensionless"/>

      <variable initial_value="10000" name="Glc" units="micromolar"/>

      <variable initial_value="0.2" name="K_2" units="dimensionless"/>

      <variable initial_value="10000" name="K_a1" units="micromolar"/>

      <variable initial_value="10000" name="K_a2" units="micromolar"/>

      <variable name="time" public_interface="in" units="minute"/>

      <math xmlns="http://www.w3.org/1998/Math/MathML">

         <apply>

            <eq/>

            <apply>

               <diff/>

               <bvar>

                  <ci>time</ci>

               </bvar>

               <ci>Pha</ci>

            </apply>

            <apply>

               <minus/>

               <apply>

                  <times/>

                  <ci>V_1</ci>

                  <apply>

                     <divide/>

                     <apply>

                        <minus/>

                        <cn xmlns:cellml="http://www.cellml.org/cellml/1.0#" cellml:units="dimensionless">1</cn>

                        <ci>Pha</ci>

                     </apply>

                     <apply>

                        <minus/>

                        <apply>

                           <plus/>

                           <ci>K_1</ci>

                           <cn xmlns:cellml="http://www.cellml.org/cellml/1.0#" cellml:units="dimensionless">1</cn>

                        </apply>

                        <ci>Pha</ci>

                     </apply>

                  </apply>

               </apply>

               <apply>

                  <divide/>

                  <apply>

                     <times/>

                     <ci>V_M2</ci>

                     <apply>

                        <plus/>

                        <cn xmlns:cellml="http://www.cellml.org/cellml/1.0#" cellml:units="dimensionless">1</cn>

                        <apply>

                           <divide/>

                           <apply>

                              <times/>

                              <ci>alpha</ci>

                              <ci>Glc</ci>

                           </apply>

                           <apply>

                              <plus/>

                              <ci>K_a1</ci>

                              <ci>Glc</ci>

                           </apply>

                        </apply>

                     </apply>

                     <ci>Pha</ci>

                  </apply>

                  <apply>

                     <plus/>

                     <apply>

                        <divide/>

                        <ci>K_2</ci>

                        <apply>

                           <plus/>

                           <cn xmlns:cellml="http://www.cellml.org/cellml/1.0#" cellml:units="dimensionless">1</cn>

                           <apply>

                              <divide/>

                              <ci>Glc</ci>

                              <ci>K_a2</ci>

                           </apply>

                        </apply>

                     </apply>

                     <ci>Pha</ci>

                  </apply>

               </apply>

            </apply>

         </apply>

      </math>

   </component>

   <component name="V_1">

      <variable name="V_1" public_interface="out" units="dimensionless"/>

      <variable initial_value="1.5" name="V_M1" units="per_minute"/>

      <variable initial_value="9" name="gamma" units="dimensionless"/>

      <variable name="Z" public_interface="in" units="dimensionless"/>

      <variable initial_value="0.5" name="K_a5" units="micromolar"/>

      <variable name="time" public_interface="in" units="minute"/>

      <math xmlns="http://www.w3.org/1998/Math/MathML">

         <apply>

            <eq/>

            <ci>V_1</ci>

            <apply>

               <times/>

               <ci>V_M1</ci>

               <apply>

                  <plus/>

                  <cn xmlns:cellml="http://www.cellml.org/cellml/1.0#" cellml:units="dimensionless">1</cn>

                  <apply>

                     <times/>

                     <ci>gamma</ci>

                     <apply>

                        <divide/>

                        <apply>

                           <power/>

                           <ci>Z</ci>

                           <cn xmlns:cellml="http://www.cellml.org/cellml/1.0#" cellml:units="dimensionless">4</cn>

                        </apply>

                        <apply>

                           <plus/>

                           <apply>

                              <power/>

                              <ci>K_a5</ci>

                              <cn xmlns:cellml="http://www.cellml.org/cellml/1.0#" cellml:units="dimensionless">4</cn>

                           </apply>

                           <apply>

                              <power/>

                              <ci>Z</ci>

                              <cn xmlns:cellml="http://www.cellml.org/cellml/1.0#" cellml:units="dimensionless">4</cn>

                           </apply>

                        </apply>

                     </apply>

                  </apply>

               </apply>

            </apply>

         </apply>

      </math>

   </component>

   <component name="K_1">

      <variable name="K_1" public_interface="out" units="dimensionless"/>

      <variable initial_value="0.1" name="K_11" units="dimensionless"/>

      <variable name="Z" public_interface="in" units="dimensionless"/>

      <variable initial_value="0.5" name="K_a6" units="micromolar"/>

      <variable name="time" public_interface="in" units="minute"/>

      <math xmlns="http://www.w3.org/1998/Math/MathML">

         <apply>

            <eq/>

            <ci>K_1</ci>

            <apply>

               <divide/>

               <ci>K_11</ci>

               <apply>

                  <plus/>

                  <cn xmlns:cellml="http://www.cellml.org/cellml/1.0#" cellml:units="dimensionless">1</cn>

                  <apply>

                     <divide/>

                     <apply>

                        <power/>

                        <ci>Z</ci>

                        <cn xmlns:cellml="http://www.cellml.org/cellml/1.0#" cellml:units="dimensionless">4</cn>

                     </apply>

                     <apply>

                        <power/>

                        <ci>K_a6</ci>

                        <cn xmlns:cellml="http://www.cellml.org/cellml/1.0#" cellml:units="dimensionless">4</cn>

                     </apply>

                  </apply>

               </apply>

            </apply>

         </apply>

      </math>

   </component>

   <component name="Z">

      <variable cmeta:id="Z_Z" name="Z" public_interface="out" units="dimensionless"/>

      <variable initial_value="0.3" name="A" units="micromolar"/>

      <variable initial_value="0.25" name="B" units="micromolar"/>

      <variable initial_value="1" name="v" units="per_minute"/>

      <variable name="time" public_interface="in" units="minute"/>

      <math xmlns="http://www.w3.org/1998/Math/MathML">

         <apply>

            <eq/>

            <ci>Z</ci>

            <apply>

               <plus/>

               <ci>A</ci>

               <apply>

                  <times/>

                  <ci>B</ci>

                  <apply>

                     <sin/>

                     <apply>

                        <times/>

                        <cn xmlns:cellml="http://www.cellml.org/cellml/1.0#" cellml:units="dimensionless">2</cn>

                        <pi/>

                        <ci>v</ci>

                        <ci>time</ci>

                     </apply>

                  </apply>

               </apply>

            </apply>

         </apply>

      </math>

   </component>

   <connection>

      <map_components component_1="Pha" component_2="environment"/>

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

   </connection>

   <connection>

      <map_components component_1="V_1" component_2="environment"/>

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

   </connection>

   <connection>

      <map_components component_1="K_1" component_2="environment"/>

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

   </connection>

   <connection>

      <map_components component_1="Z" component_2="environment"/>

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

   </connection>

   <connection>

      <map_components component_1="Pha" component_2="V_1"/>

      <map_variables variable_1="V_1" variable_2="V_1"/>

   </connection>

   <connection>

      <map_components component_1="K_1" component_2="Pha"/>

      <map_variables variable_1="K_1" variable_2="K_1"/>

   </connection>

   <connection>

      <map_components component_1="K_1" component_2="Z"/>

      <map_variables variable_1="Z" variable_2="Z"/>

   </connection>

   <connection>

      <map_components component_1="V_1" component_2="Z"/>

      <map_variables variable_1="Z" variable_2="Z"/>

   </connection>



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

  <rdf:Description rdf:about="">

    <dc:creator rdf:parseType="Resource">

      <vCard:N rdf:parseType="Resource">

        <vCard:Family>Nielsen</vCard:Family>

        <vCard:Given>Hanne</vCard:Given>

    

      </vCard:N>

      <vCard:EMAIL rdf:parseType="Resource">

        <rdf:value>hnie010@aucklanduni.ac.nz</rdf:value>

        <rdf:type rdf:resource="http://imc.org/vCard/3.0#internet"/>

      </vCard:EMAIL>

      <vCard:ORG rdf:parseType="Resource">

        <vCard:Orgname>The University of Auckland</vCard:Orgname>

        <vCard:Orgunit>Auckland Bioengineering Institute</vCard:Orgunit>

      </vCard:ORG>

    </dc:creator>

    <dcterms:created rdf:parseType="Resource">

      <dcterms:W3CDTF>2009-10-08</dcterms:W3CDTF>

    </dcterms:created>

  </rdf:Description>

  <rdf:Description rdf:about="#gall_2000">

    <cmeta:species>Human</cmeta:species>

    <cmeta:bio_entity>Liver</cmeta:bio_entity>

    <cmeta:bio_entity>hepatocyte</cmeta:bio_entity>

    <bqs:reference rdf:parseType="Resource">

      <dc:subject rdf:parseType="Resource">

        <bqs:subject_type>keyword</bqs:subject_type>

        <rdf:value>

          <rdf:Bag>

            <rdf:li>hepatology</rdf:li>

            <rdf:li>liver</rdf:li>

          </rdf:Bag>

        </rdf:value>

      </dc:subject>

    </bqs:reference>

    <bqs:reference rdf:parseType="Resource">

      <bqs:Pubmed_id> 11093832 </bqs:Pubmed_id>

      <bqs:JournalArticle rdf:parseType="Resource">

        <dc:creator>

          <rdf:Seq>

            <rdf:li rdf:parseType="Resource">

              <bqs:Person rdf:parseType="Resource">

                <vCard:N rdf:parseType="Resource">

                  <vCard:Family>Gall</vCard:Family>

                  <vCard:Given>D</vCard:Given>

                </vCard:N>

              </bqs:Person>

            </rdf:li>

            <rdf:li rdf:parseType="Resource">

              <bqs:Person rdf:parseType="Resource">

                <vCard:N rdf:parseType="Resource">

                  <vCard:Family>Baus</vCard:Family>

                  <vCard:Given>E</vCard:Given>

                </vCard:N>

              </bqs:Person>

            </rdf:li>

            <rdf:li rdf:parseType="Resource">

              <bqs:Person rdf:parseType="Resource">

                <vCard:N rdf:parseType="Resource">

                  <vCard:Family>Dupont</vCard:Family>

                  <vCard:Given>G</vCard:Given>

                </vCard:N>

              </bqs:Person>

            </rdf:li>

                      </rdf:Seq>

        </dc:creator>

        <dc:title>

           Activation of the liver glycogen phosphorylase by Ca(2+)oscillations: a theoretical study

          </dc:title>

        <dcterms:issued rdf:parseType="Resource">

          <dcterms:W3CDTF>2009-07-08</dcterms:W3CDTF>

        </dcterms:issued>

        <bqs:Journal rdf:parseType="Resource">

          <dc:title>Journal of Theoretical Biology</dc:title>

        </bqs:Journal>

        <bqs:volume>207(4)</bqs:volume>

        <bqs:first_page>445</bqs:first_page>

        <bqs:last_page>454</bqs:last_page>

      </bqs:JournalArticle>

    </bqs:reference>

  </rdf:Description>

</rdf:RDF>





</model>