Rendering of the source text

<?xml version='1.0' encoding='utf-8'?>
<!--  FILE :  saucerman_model_2004.xml

CREATED :  5th December 2003

LAST MODIFIED : 5th December 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 Saucerman and McCulloch's 2004 mathematical model of myocyte adrenergic regulation. 

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="saucerman_mcculloch_2004_version01" name="saucerman_mcculloch_2004_version01">
<documentation xmlns="http://cellml.org/tmp-documentation">
<article>
  <articleinfo>
  <title>Modelling Cell Signalling Networks: A Case Study Of Myocyte Adrenergic Regulation</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>
Signal transduction pathways form communication networks in the cell.  By transducing a range of environmental cues such as hormones and neurotransmitters, they coordinate many of the physiologicval reposnses to changes in the cell environment.  In comparision with metabolism, signalling networks are poorly characterised.  They account for a large portion of biological complexity, and understanding the function of these complex signalling networks presents a challenge to modern biology, requiring a combined approach of experimental analysis and modelling.  
</para>

<para>
Systems models of cell signalling can be considered at two levels of detail: abstract top-down models and mechansistic systems analyses.  Top-down modelling, often based on protein interaction data, is useful for elucidating qualitative, topological features of signalling networks.  Mechanistic systems models usually describe the biochemical reactions with kinetic rate laws and differential equations.  There are several different approaches for devloping mechanistic systems models of signal transduction.  These different methods are reviewed by Saucerman and McCulloch in the 2004 publication described here.  As a case study of model devlopment and analysis, they examine the funcyional roles of phospholamban, the L-type calcium channel, the ryanodine receptor, and troponin I phosphorylation upon beta-adrenergic stimulation in the rat ventricular myocyte (see the figure below). 
</para>

<para>
Model analysis revealed that although protein kinase A-mediated phosphorylation of the ryanodine receptor greatly increases its calcium sensitivity, calcium autoregulation may adapt quickly be negating potential increases in contractility.  The authors concluded that phospholamban phosphorylation is the main mechanism for increased sarcoplasmic reticulum load and calcium relaxation rate during beta-adrenergic stimulation, whereas both phospholamban and the L-type calcium channle contribute to increased systolic calcium.
</para>

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

<para>
<ulink url="http://www.sciencedirect.com/science?_ob=ArticleURL&amp;_udi=B6TBN-4BT7D69-1&amp;_user=140507&amp;_coverDate=07%2F31%2F2004&amp;_alid=185464983&amp;_rdoc=1&amp;_fmt=summary&amp;_orig=search&amp;_qd=1&amp;_cdi=5147&amp;_sort=d&amp;_docanchor=&amp;view=c&amp;_acct=C000011498&amp;_version=1&amp;_urlVersion=0&amp;_userid=140507&amp;md5=5b437e8da921cae465fe5ea35228a7cc">Mechanistic systems models of cell signalling networks: a case study of nyocyte adrenergic regulation</ulink>, Jeffrey J. Saucerman and Andrew D. McCulloch, 2000, <ulink url="http://www.sciencedirect.com/science?_ob=JournalURL&amp;_cdi=5147&amp;_auth=y&amp;_acct=C000011498&amp;_version=1&amp;_urlVersion=0&amp;_userid=140507&amp;md5=eb4fbcd5c55fb3c855c77926d52f09d2">
            <emphasis>Progress in Biophysics and Molecular Biology</emphasis>
          </ulink>, 11, 369-391.  (<ulink url="http://www.sciencedirect.com/science?_ob=ArticleURL&amp;_udi=B6TBN-4BT7D69-1&amp;_coverDate=07%2F31%2F2004&amp;_alid=185464983&amp;_rdoc=1&amp;_fmt=&amp;_orig=search&amp;_qd=1&amp;_cdi=5147&amp;_sort=d&amp;view=c&amp;_acct=C000011498&amp;_version=1&amp;_urlVersion=0&amp;_userid=140507&amp;md5=3b23af7b7dd3e4e85c6012c1b6315c74">Full text (HTML)</ulink> and PDF versions of the article are available on the <emphasis>Progress in Biophysics and Molecular Biology</emphasis> website.)  <ulink url="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&amp;db=PubMed&amp;list_uids=15142747&amp;dopt=Abstract">PubMed ID: 15142747</ulink>
</para>

<informalfigure float="0" id="fig_cell_diagram">
<mediaobject>
  <imageobject>
    <objectinfo>
      <title>cell diagram</title>
    </objectinfo>
    <imagedata fileref="saucerman_mcculloch_2004.png"/>
  </imageobject>
</mediaobject>
<caption>Schematic diagram of the beta1-adrenergic signalling ntework and its regulation of rat ventricular myocyte excitation-contraction coupling.</caption>
</informalfigure>

</sect1>
</article>
</documentation>
  
  
  
  <units name="micromolar">
    <unit units="mole" prefix="micro"/>
    <unit units="litre" exponent="-1"/>
  </units>
  
  <units name="first_order_rate_constant">
    <unit units="second" exponent="-1"/>
  </units>
  
  
  <component name="environment">
    <variable units="second" public_interface="out" name="time"/>
  </component>
  
  <component name="PKACII_RyR"> 
    <variable units="micromolar" public_interface="out" name="PKACII_RyR"/>
    
    <variable units="micromolar" name="PKACII_RyRtot" initial_value="0.034"/>
    
    <variable units="micromolar" public_interface="in" name="RyR"/>
    <variable units="micromolar" public_interface="in" name="Ks_RyR_PKAC"/>
    <variable units="dimensionless" public_interface="in" name="epsilon"/>
    
    <math xmlns="http://www.w3.org/1998/Math/MathML">
      <apply>
        <eq/> 
        <ci> PKACII_RyR </ci> 
        <apply>
          <plus/>
          <ci> PKACII_RyRtot </ci>
          <apply>
            <divide/>
            <apply>
              <times/>
              <ci> epsilon </ci>
              <ci> RyR </ci>
              <ci> PKACII_RyR </ci>
            </apply>
            <ci> Ks_RyR_PKAC </ci>
          </apply>
        </apply>
      </apply> 
    </math>
  </component>
  
  <component name="PP1_RyR"> 
    <variable units="micromolar" public_interface="out" name="PP1_RyR"/>
    
    <variable units="micromolar" name="PP1_RyRtot" initial_value="0.034"/>
    
    <variable units="micromolar" public_interface="in" name="RyRp"/>
    <variable units="micromolar" public_interface="in" name="Ks_RyR_PP1"/>
    <variable units="dimensionless" public_interface="in" name="epsilon"/>
    
    <math xmlns="http://www.w3.org/1998/Math/MathML">
      <apply>
        <eq/> 
        <ci> PP1_RyR </ci> 
        <apply>
          <plus/>
          <ci> PP1_RyRtot </ci>
          <apply>
            <divide/>
            <apply>
              <times/>
              <ci> epsilon </ci>
              <ci> RyRp </ci>
              <ci> PP1_RyR </ci>
            </apply>
            <ci> Ks_RyR_PP1 </ci>
          </apply>
        </apply>
      </apply> 
    </math>
  </component>
  
  <component name="PP2A_RyR"> 
    <variable units="micromolar" public_interface="out" name="PP2A_RyR"/>
    
    <variable units="micromolar" name="PP2A_RyRtot" initial_value="0.034"/>
    
    <variable units="micromolar" public_interface="in" name="RyRp"/>
    <variable units="micromolar" public_interface="in" name="Ks_RyR_PP2A"/>
    <variable units="dimensionless" public_interface="in" name="epsilon"/>
    
    <math xmlns="http://www.w3.org/1998/Math/MathML">
      <apply>
        <eq/> 
        <ci> PP2A_RyR </ci> 
        <apply>
          <plus/>
          <ci> PP2A_RyRtot </ci>
          <apply>
            <divide/>
            <apply>
              <times/>
              <ci> epsilon </ci>
              <ci> RyRp </ci>
              <ci> PP2A_RyR </ci>
            </apply>
            <ci> Ks_RyR_PP2A </ci>
          </apply>
        </apply>
      </apply> 
    </math>
  </component>
  
  <component name="RyR"> 
    <variable units="micromolar" public_interface="out" name="RyR"/>
    
    <variable units="micromolar" public_interface="in" name="RyRtot"/>
    <variable units="micromolar" public_interface="in" name="PKACII_RyR"/>
    <variable units="micromolar" public_interface="in" name="Ks_RyR_PKAC"/>
    <variable units="dimensionless" public_interface="in" name="epsilon"/>
    
    <math xmlns="http://www.w3.org/1998/Math/MathML">
      <apply>
        <eq/> 
        <ci> RyR </ci> 
        <apply>
          <plus/>
          <ci> RyRtot </ci>
          <apply>
            <divide/>
            <apply>
              <times/>
              <ci> epsilon </ci>
              <ci> RyR </ci>
              <ci> PKACII_RyR </ci>
            </apply>
            <ci> Ks_RyR_PKAC </ci>
          </apply>
        </apply>
      </apply> 
    </math>
  </component>
  
  <component name="RyRp"> 
    <variable units="micromolar" public_interface="out" name="RyRp"/>
    
    <variable units="micromolar" public_interface="in" name="RyRptot"/>
    <variable units="micromolar" public_interface="in" name="PP1_RyR"/>
    <variable units="micromolar" public_interface="in" name="PP2A_RyR"/>
    <variable units="micromolar" public_interface="in" name="Ks_RyR_PP1"/>
    <variable units="micromolar" public_interface="in" name="Ks_RyR_PP2A"/>
    <variable units="dimensionless" public_interface="in" name="epsilon"/>
    
    <math xmlns="http://www.w3.org/1998/Math/MathML">
      <apply>
        <eq/> 
        <ci> RyRp </ci> 
        <apply>
          <plus/>
          <ci> RyRptot </ci>
          <apply>
            <divide/>
            <apply>
              <times/>
              <ci> epsilon </ci>
              <ci> RyRp </ci>
              <ci> PP1_RyR </ci>
            </apply>
            <ci> Ks_RyR_PP1 </ci>
          </apply>
          <apply>
            <divide/>
            <apply>
              <times/>
              <ci> epsilon </ci>
              <ci> RyRp </ci>
              <ci> PP2A_RyR </ci>
            </apply>
            <ci> Ks_RyR_PP2A </ci>
          </apply>
        </apply>
      </apply> 
    </math>
  </component>
  
  <component name="RyRtot"> 
    <variable units="micromolar" public_interface="out" name="RyRtot"/>
    
    <variable units="micromolar" public_interface="in" name="RyRsum"/>
    <variable units="micromolar" public_interface="in" name="RyRptot"/>
    
    <math xmlns="http://www.w3.org/1998/Math/MathML">
      <apply>
        <eq/> 
        <ci> RyRtot </ci> 
        <apply>
          <minus/>
          <ci> RyRsum </ci>
          <ci> RyRptot </ci>
        </apply>
      </apply> 
    </math>
  </component>
    
  <component name="RyRptot"> 
    <variable units="micromolar" public_interface="out" name="RyRptot"/>
    
    <variable units="first_order_rate_constant" name="kPKA_RyR" initial_value="54.0"/>
    <variable units="first_order_rate_constant" name="kPP1_RyR" initial_value="8.52"/>
    <variable units="first_order_rate_constant" name="kPP2A_RyR" initial_value="10.1"/>
    
    <variable units="micromolar" public_interface="in" name="RyR"/>
    <variable units="micromolar" public_interface="in" name="RyRp"/>
    <variable units="micromolar" public_interface="in" name="PP1_RyR"/>
    <variable units="micromolar" public_interface="in" name="PP2A_RyR"/>
    <variable units="micromolar" public_interface="in" name="PKACII_RyR"/>
    <variable units="micromolar" public_interface="in" name="Ks_RyR_PP1"/>
    <variable units="micromolar" public_interface="in" name="Ks_RyR_PP2A"/>
    <variable units="micromolar" public_interface="in" name="Ks_RyR_PKAC"/>
    <variable units="dimensionless" public_interface="in" name="epsilon"/>
    <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>RyRptot</ci> 
        </apply>  
        <apply>
          <minus/>
          <apply>
            <times/>
            <ci> kPKA_RyR </ci>
            <apply>
              <divide/>
              <apply>
                <times/>
                <ci> epsilon </ci>
                <ci> RyR </ci>
                <ci> PKACII_RyR </ci>
              </apply>
              <ci> Ks_RyR_PKAC </ci>
            </apply>
          </apply>
          <apply>
            <plus/>
            <apply>
              <times/>
              <ci> kPP1_RyR </ci>
              <apply>
                <divide/>
                <apply>
                  <times/>
                  <ci> epsilon </ci>
                  <ci> RyRp </ci>
                  <ci> PP1_RyR </ci>
                </apply>
                <ci> Ks_RyR_PP1 </ci>
              </apply>
            </apply>
            <apply>
              <times/>
              <ci> kPP2A_RyR </ci>
              <apply>
                <divide/>
                <apply>
                  <times/>
                  <ci> epsilon </ci>
                  <ci> RyRp </ci>
                  <ci> PP2A_RyR </ci>
                </apply>
                <ci> Ks_RyR_PP2A </ci>
              </apply>
            </apply>
          </apply>
        </apply>
      </apply> 
    </math>
  </component>
  
  <component name="KMrel"> 
    <variable units="micromolar" public_interface="out" name="KMrel"/>
    
    <variable units="micromolar" name="KMrel0"/>
    
    <variable units="micromolar" public_interface="in" name="RyRsum"/>
    <variable units="micromolar" public_interface="in" name="RyRptot"/>
    
    <math xmlns="http://www.w3.org/1998/Math/MathML">
      <apply>
        <eq/> 
        <ci> KMrel </ci> 
        <apply>
          <times/>
          <apply>
            <divide/>
            <cn cellml:units="dimensionless"> 1.64 </cn>
            <apply>
              <plus/>
              <cn cellml:units="dimensionless"> 1.0 </cn>
              <apply>
                <divide/>
                <ci> RyRptot </ci>
                <ci> RyRsum </ci>
              </apply>
            </apply>
          </apply>
          <ci> KMrel0 </ci>
        </apply>  
      </apply> 
    </math>
  </component>
  
  <component name="TnI"> 
    <variable units="micromolar" public_interface="out" name="TnI"/>
    
    <variable units="micromolar" public_interface="in" name="TnItot"/>
    <variable units="micromolar" public_interface="in" name="TnIp"/>
    
    <math xmlns="http://www.w3.org/1998/Math/MathML">
      <apply>
        <eq/> 
        <ci> TnI </ci> 
        <apply>
          <minus/>
          <ci> TnItot </ci>
          <ci> TnIp </ci>
        </apply>
      </apply> 
    </math>
  </component>
    
  <component name="TnIp"> 
    <variable units="micromolar" public_interface="out" name="TnIp"/>
    
    <variable units="first_order_rate_constant" name="kPKA_TnI" initial_value="54.0"/>
    <variable units="first_order_rate_constant" name="kPP2A_TnI" initial_value="10.1"/>
    <variable units="micromolar" name="KM_PKA_TnI" initial_value="21.0"/>
    <variable units="micromolar" name="KM_PP2A_TnI" initial_value="3.0"/>
    <variable units="micromolar" name="PKAC"/>
    <variable units="micromolar" name="PP2A"/>
    
    <variable units="micromolar" public_interface="in" name="TnI"/>
    <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>TnIp</ci> 
        </apply>  
        <apply>
          <minus/>
          <apply>
            <divide/>
            <apply>
              <times/>
              <ci> kPKA_TnI </ci>
              <ci> PKAC </ci>
              <ci> TnI </ci>
            </apply>
            <apply>
              <plus/>
              <ci> KM_PKA_TnI </ci>
              <ci> TnIp </ci>
            </apply> 
          </apply>
          <apply>
            <divide/>
            <apply>
              <times/>
              <ci> kPP2A_TnI </ci>
              <ci> PP2A </ci>
              <ci> TnIp </ci>
            </apply>
            <apply>
              <plus/>
              <ci> KM_PP2A_TnI </ci>
              <ci> TnIp </ci>
            </apply>
          </apply>
        </apply>
      </apply> 
    </math>
  </component>
  
  <component name="KMTnC"> 
    <variable units="micromolar" public_interface="out" name="KMTnC"/>
    
    <variable units="micromolar" name="KMTnC0"/>
    
    <variable units="micromolar" public_interface="in" name="TnIp"/>
    <variable units="micromolar" public_interface="in" name="TnItot"/>
    
    <math xmlns="http://www.w3.org/1998/Math/MathML">
      <apply>
        <eq/> 
        <ci> KMTnC </ci> 
        <apply>
          <times/>
          <apply>
            <plus/>
            <cn cellml:units="dimensionless"> 1.0 </cn>
            <cn cellml:units="dimensionless"> 0.45 </cn>
            <apply>
              <divide/>
              <ci> TnIp </ci>
              <ci> TnItot </ci>
            </apply>
          </apply>
          <ci> KMTnC0 </ci>
        </apply>  
      </apply> 
    </math>
  </component>
  
  <component name="kinetic_parameters"> 
    <variable units="dimensionless" public_interface="out" name="epsilon" initial_value="10.0"/>
    <variable units="micromolar" public_interface="out" name="RyRsum" initial_value="0.135"/>
    <variable units="micromolar" public_interface="out" name="Ks_RyR_PKAC" initial_value="21.0"/>
    <variable units="micromolar" public_interface="out" name="Ks_RyR_PP1" initial_value="7.0"/>
    <variable units="micromolar" public_interface="out" name="Ks_RyR_PP2A" initial_value="4.1"/>
    <variable units="micromolar" public_interface="out" name="TnItot" initial_value="70.0"/>
  </component>
  
  
  <connection>
    <map_components component_2="environment" component_1="RyRptot"/>
    <map_variables variable_2="time" variable_1="time"/>
  </connection>
  
  <connection>
    <map_components component_2="environment" component_1="TnIp"/>
    <map_variables variable_2="time" variable_1="time"/>
  </connection>
  
  <connection>
    <map_components component_2="RyR" component_1="PKACII_RyR"/>
    <map_variables variable_2="RyR" variable_1="RyR"/>
    <map_variables variable_2="PKACII_RyR" variable_1="PKACII_RyR"/>
  </connection>
  
  <connection>
    <map_components component_2="kinetic_parameters" component_1="PKACII_RyR"/>
    <map_variables variable_2="epsilon" variable_1="epsilon"/>
    <map_variables variable_2="Ks_RyR_PKAC" variable_1="Ks_RyR_PKAC"/>
  </connection>
  
  <connection>
    <map_components component_2="RyRp" component_1="PP1_RyR"/>
    <map_variables variable_2="RyRp" variable_1="RyRp"/>
    <map_variables variable_2="PP1_RyR" variable_1="PP1_RyR"/>
  </connection>
  
  <connection>
    <map_components component_2="kinetic_parameters" component_1="PP1_RyR"/>
    <map_variables variable_2="epsilon" variable_1="epsilon"/>
    <map_variables variable_2="Ks_RyR_PP1" variable_1="Ks_RyR_PP1"/>
  </connection>
  
  <connection>
    <map_components component_2="RyRp" component_1="PP2A_RyR"/>
    <map_variables variable_2="RyRp" variable_1="RyRp"/>
    <map_variables variable_2="PP2A_RyR" variable_1="PP2A_RyR"/>
  </connection>
  
  <connection>
    <map_components component_2="kinetic_parameters" component_1="PP2A_RyR"/>
    <map_variables variable_2="epsilon" variable_1="epsilon"/>
    <map_variables variable_2="Ks_RyR_PP2A" variable_1="Ks_RyR_PP2A"/>
  </connection>
  
  <connection>
    <map_components component_2="kinetic_parameters" component_1="RyR"/>
    <map_variables variable_2="epsilon" variable_1="epsilon"/>
    <map_variables variable_2="Ks_RyR_PKAC" variable_1="Ks_RyR_PKAC"/>
  </connection>
 
  <connection>
    <map_components component_2="RyRptot" component_1="RyRp"/>
    <map_variables variable_2="RyRptot" variable_1="RyRptot"/>
    <map_variables variable_2="RyRp" variable_1="RyRp"/>
  </connection>
  
  <connection>
    <map_components component_2="kinetic_parameters" component_1="RyRp"/>
    <map_variables variable_2="epsilon" variable_1="epsilon"/>
    <map_variables variable_2="Ks_RyR_PP2A" variable_1="Ks_RyR_PP2A"/>
    <map_variables variable_2="Ks_RyR_PP1" variable_1="Ks_RyR_PP1"/>
  </connection>
  
  <connection>
    <map_components component_2="RyR" component_1="RyRptot"/>
    <map_variables variable_2="RyR" variable_1="RyR"/>
  </connection>
  
  <connection>
    <map_components component_2="RyR" component_1="RyRtot"/>
    <map_variables variable_2="RyRtot" variable_1="RyRtot"/>
  </connection>
  
  <connection>
    <map_components component_2="PKACII_RyR" component_1="RyRptot"/>
    <map_variables variable_2="PKACII_RyR" variable_1="PKACII_RyR"/>
  </connection>
  
  <connection>
    <map_components component_2="PP1_RyR" component_1="RyRptot"/>
    <map_variables variable_2="PP1_RyR" variable_1="PP1_RyR"/>
  </connection>
  
  <connection>
    <map_components component_2="PP2A_RyR" component_1="RyRptot"/>
    <map_variables variable_2="PP2A_RyR" variable_1="PP2A_RyR"/>
  </connection>
  
  <connection>
    <map_components component_2="kinetic_parameters" component_1="RyRptot"/>
    <map_variables variable_2="epsilon" variable_1="epsilon"/>
    <map_variables variable_2="Ks_RyR_PKAC" variable_1="Ks_RyR_PKAC"/>
    <map_variables variable_2="Ks_RyR_PP2A" variable_1="Ks_RyR_PP2A"/>
    <map_variables variable_2="Ks_RyR_PP1" variable_1="Ks_RyR_PP1"/>
  </connection>
  
  <connection>
    <map_components component_2="RyRptot" component_1="RyRtot"/>
    <map_variables variable_2="RyRptot" variable_1="RyRptot"/>
  </connection>
  
  <connection>
    <map_components component_2="kinetic_parameters" component_1="RyRtot"/>
    <map_variables variable_2="RyRsum" variable_1="RyRsum"/>
  </connection>
  
  <connection>
    <map_components component_2="kinetic_parameters" component_1="KMrel"/>
    <map_variables variable_2="RyRsum" variable_1="RyRsum"/>
  </connection>
  
  <connection>
    <map_components component_2="RyRptot" component_1="KMrel"/>
    <map_variables variable_2="RyRptot" variable_1="RyRptot"/>
  </connection>
  
  <connection>
    <map_components component_2="TnI" component_1="TnIp"/>
    <map_variables variable_2="TnI" variable_1="TnI"/>
    <map_variables variable_2="TnIp" variable_1="TnIp"/>
  </connection>
  
  <connection>
    <map_components component_2="kinetic_parameters" component_1="TnI"/>
    <map_variables variable_2="TnItot" variable_1="TnItot"/>
  </connection>
  
  <connection>
    <map_components component_2="TnIp" component_1="KMTnC"/>
    <map_variables variable_2="TnIp" variable_1="TnIp"/>
  </connection>
  
  <connection>
    <map_components component_2="kinetic_parameters" component_1="KMTnC"/>
    <map_variables variable_2="TnItot" variable_1="TnItot"/>
  </connection>
  

<rdf:RDF>
  <rdf:Bag rdf:about="rdf:#2ca6311b-0909-408d-9f4f-7836e6c674b9">
    <rdf:li>mechanics</rdf:li>
    <rdf:li>Cardiac Myocyte</rdf:li>
    <rdf:li>pharmacology</rdf:li>
    <rdf:li>signal transduction</rdf:li>
    <rdf:li>gpcr</rdf:li>
    <rdf:li>metabolism</rdf:li>
    <rdf:li>cardiac myocyte</rdf:li>
    <rdf:li>electrophysiology</rdf:li>
    <rdf:li>cardiac</rdf:li>
    <rdf:li>beta-adrenoreceptor</rdf:li>
  </rdf:Bag>
  <rdf:Seq rdf:about="rdf:#fcdd675f-f036-4549-b766-523bfddfaa4f">
    <rdf:li rdf:resource="rdf:#3ea1eba5-ac5c-4951-96e5-48ad5cdb2177"/>
    <rdf:li rdf:resource="rdf:#0afff1c6-74e4-4c9c-a9d9-7878957bdb4d"/>
  </rdf:Seq>
  <rdf:Description rdf:about="rdf:#71724774-19fd-4571-b35e-0f04ba71e702">
    <dc:title>Progress in Biopysics and Molecular Biology</dc:title>
  </rdf:Description>
  <rdf:Description rdf:about="rdf:#3ea1eba5-ac5c-4951-96e5-48ad5cdb2177">
    <rdf:type rdf:resource="http://www.cellml.org/bqs/1.0#Person"/>
    <vCard:N rdf:resource="rdf:#bcf44153-948a-44e8-adf2-336c2cba4d9b"/>
  </rdf:Description>
  <rdf:Description rdf:about="rdf:#06fc809b-a8a1-456f-ae9a-1ac6514cb0aa">
    <dc:title>
            Mechanistic systems models of cell signaling networks: a case study 
            of myocyte adrenergic regulation
          </dc:title>
    <dcterms:issued rdf:resource="rdf:#fe040b40-fe3a-426d-bcb7-15563a558707"/>
    <bqs:Journal rdf:resource="rdf:#71724774-19fd-4571-b35e-0f04ba71e702"/>
    <dc:creator rdf:resource="rdf:#fcdd675f-f036-4549-b766-523bfddfaa4f"/>
  </rdf:Description>
  <rdf:Description rdf:about="rdf:#83d44bcb-eba1-40ae-9629-b419744cce2f">
    <vCard:Orgname>The University of Auckland</vCard:Orgname>
    <vCard:Orgunit>The Bioengineering Institute</vCard:Orgunit>
  </rdf:Description>
  <rdf:Description rdf:about="rdf:#b7b1a11c-de72-4ba4-81ef-e41028bcc8d3">
    <vCard:Given>Catherine</vCard:Given>
    <vCard:Family>Lloyd</vCard:Family>
    <vCard:Other>May</vCard:Other>
  </rdf:Description>
  <rdf:Description rdf:about="">
    <dc:publisher>
        The University of Auckland, Bioengineering Institute
      </dc:publisher>
    <dcterms:created rdf:resource="rdf:#74940bfc-c232-4507-b5e4-42b323cc5afa"/>
    <dc:creator rdf:resource="rdf:#32c538c2-93da-4a2b-8f34-58c80b7d3870"/>
  </rdf:Description>
  <rdf:Description rdf:about="rdf:#32c538c2-93da-4a2b-8f34-58c80b7d3870">
    <vCard:ORG rdf:resource="rdf:#83d44bcb-eba1-40ae-9629-b419744cce2f"/>
    <vCard:EMAIL rdf:resource="rdf:#e5e737ae-bcdb-4d36-8ea6-95dd6c7d602b"/>
    <vCard:N rdf:resource="rdf:#b7b1a11c-de72-4ba4-81ef-e41028bcc8d3"/>
  </rdf:Description>
  <rdf:Description rdf:about="rdf:#0afff1c6-74e4-4c9c-a9d9-7878957bdb4d">
    <rdf:type rdf:resource="http://www.cellml.org/bqs/1.0#Person"/>
    <vCard:N rdf:resource="rdf:#7c44ca73-99ec-4174-92d6-f31484d660c3"/>
  </rdf:Description>
  <rdf:Description rdf:about="rdf:#22a1b4d8-3f4a-4e47-b746-0ec845d213e9">
    <vCard:FN>Catherine Lloyd</vCard:FN>
  </rdf:Description>
  <rdf:Description rdf:about="rdf:#8bd78a6c-72e8-44fc-a89d-7693ebf21c1d">
    <bqs:JournalArticle rdf:resource="rdf:#06fc809b-a8a1-456f-ae9a-1ac6514cb0aa"/>
  </rdf:Description>
  <rdf:Description rdf:about="rdf:#74940bfc-c232-4507-b5e4-42b323cc5afa">
    <dcterms:W3CDTF>2003-12-05</dcterms:W3CDTF>
  </rdf:Description>
  <rdf:Description rdf:about="rdf:#7c44ca73-99ec-4174-92d6-f31484d660c3">
    <vCard:Given>Andrew</vCard:Given>
    <vCard:Family>McCulloch</vCard:Family>
    <vCard:Other>D</vCard:Other>
  </rdf:Description>
  <rdf:Description rdf:about="rdf:#fe040b40-fe3a-426d-bcb7-15563a558707">
    <dcterms:W3CDTF>2004</dcterms:W3CDTF>
  </rdf:Description>
  <rdf:Description rdf:about="rdf:#e5e737ae-bcdb-4d36-8ea6-95dd6c7d602b">
    <rdf:type rdf:resource="http://imc.org/vCard/3.0#internet"/>
    <rdf:value>c.lloyd@auckland.ac.nz</rdf:value>
  </rdf:Description>
  <rdf:Description rdf:about="rdf:#bcf44153-948a-44e8-adf2-336c2cba4d9b">
    <vCard:Given>Jeffrey</vCard:Given>
    <vCard:Family>Saucerman</vCard:Family>
    <vCard:Other>J</vCard:Other>
  </rdf:Description>
  <rdf:Description rdf:about="rdf:#94eae033-b2a3-472e-9fb9-9ef80804897f">
    <dc:subject rdf:resource="rdf:#3f59ef54-d059-46a9-8232-a55b05284d6c"/>
  </rdf:Description>
  <rdf:Description rdf:about="rdf:#c49e1b8b-1f06-48c6-85eb-51d2babb94ed">
    <dc:creator rdf:resource="rdf:#22a1b4d8-3f4a-4e47-b746-0ec845d213e9"/>
    <rdf:value>
          This is the CellML description of Saucerman and McCulloch's 2004 
          mathematical model of myocyte adrenergic regulation.
        </rdf:value>
  </rdf:Description>
  <rdf:Description rdf:about="rdf:#3f59ef54-d059-46a9-8232-a55b05284d6c">
    <bqs:subject_type>keyword</bqs:subject_type>
    <rdf:value rdf:resource="rdf:#2ca6311b-0909-408d-9f4f-7836e6c674b9"/>
  </rdf:Description>
  <rdf:Description rdf:about="#saucerman_mcculloch_2004_version01">
    <dc:title>
        Saucerman and McCulloch's 2004 mathematical model of myocyte adrenergic 
        regulation.
      </dc:title>
    <cmeta:bio_entity>Cardiac Myocyte</cmeta:bio_entity>
    <cmeta:comment rdf:resource="rdf:#c49e1b8b-1f06-48c6-85eb-51d2babb94ed"/>
    <bqs:reference rdf:resource="rdf:#8bd78a6c-72e8-44fc-a89d-7693ebf21c1d"/>
    <bqs:reference rdf:resource="rdf:#94eae033-b2a3-472e-9fb9-9ef80804897f"/>
  </rdf:Description>
</rdf:RDF>
</model>