Rendering of the source text

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<!--  FILE :  chang_model_1999_version02.xml

CREATED :  28th May 2007

LAST MODIFIED : 28th May 2007

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

DESCRIPTION :  This file contains a CellML description of Chang and Fujita's 1999 kinetic model of the thiazide-sensitive Na-Cl cotransporter of the renal distal tubule.

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="chang_model_1999_version02" name="chang_fujita_1999_version03">
<documentation xmlns="http://cellml.org/tmp-documentation">
<article>
  <articleinfo>
  <title>A Kinetic Model of the Thiazide-Sensitive Na-Cl Cotransporter</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>
            The new version of this model has been re-coded to remove the reaction element and replace it with a simple MathML description of the model reaction kinetics.  This is thought to be truer to the original publication, and information regarding the enzyme kinetics etc will later be added to the metadata through use of an ontology.
          </para>
  </section>
  <sect1 id="sec_structure">
<title>Model Structure</title>

<para>
ABSTRACT: The aim of this study was to construct a numerical model of the thiazide-sensitive Na-Cl cotransporter (TSC) that can predict kinetics of thiazide binding and substrate transport of TSC. We hypothesized that the mechanisms underlying these kinetic properties can be approximated by a state diagram in which the transporter has two binding sites, one for sodium and another for chloride and thiazide. On the basis of the state diagram, a system of linear equations that should be satisfied in the steady state was postulated. Numerical solution of these equations yielded model prediction of kinetics of thiazide binding and substrate transport. Rate constants, which determine transitional rates between states, were systematically adjusted to minimize a penalty function that was devised to quantitatively estimate the difference between model predictions and experimental results. With the resultant rate constants, the model could simulate the following experimental results: 1) dissociation constant of thiazide in the absence of sodium and chloride; 2) inhibitory effect of chloride on thiazide binding; 3) stimulatory effect of sodium on thiazide binding; 4) combined effects of sodium and chloride on thiazide binding; 5) dependence of sodium influx on extracellular sodium and chloride; and 6) inhibition of sodium influx by extracellular thiazide. We conclude that known kinetic properties of TSC can be predicted by a model which is based on a state diagram.
</para>

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

<para>
<ulink url="http://ajprenal.physiology.org/cgi/content/abstract/276/6/F952">A kinetic model of the thiazide-sensitive Na-Cl cotransporter</ulink>, Hangil Chang and Toshiro Fujita, 1999, <ulink url="http://ajprenal.physiology.org/">
            <emphasis>American Journal of Physiology</emphasis>
          </ulink>, 276, F952-F959.  (<ulink url="http://ajprenal.physiology.org/cgi/reprint/276/6/F952.pdf">PDF</ulink> and <ulink url="http://ajprenal.physiology.org/cgi/content/full/276/6/F952">full text</ulink> versions of the article are available to subscribers on the journal website.)  <ulink url="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&amp;db=PubMed&amp;list_uids=10362783&amp;dopt=Abstract">PubMed ID: 10362783</ulink>
</para>

<informalfigure float="0" id="fig_reaction_diagram">
<mediaobject>
  <imageobject>
    <objectinfo>
      <title>diagram of the model</title>
    </objectinfo>
    <imagedata fileref="chang_1999.png"/>
  </imageobject>
</mediaobject>
<caption>State diagram for the thiazide-sensitive Na-Cl cotransporter (TSC).  Transporter (E) has binding sites for sodium (Na ) and chloride (Cl).  Thiazide diuretics (D) compete with chloride for the same binding site.  <emphasis>_i</emphasis> is used to indicate which symbols belong to the intracellular side.</caption>
</informalfigure>

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


  
  
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  <component name="ECl_" cmeta:id="ECl_">
     
    <variable units="millimolar" public_interface="out" name="ECl_"/> 
    
    <variable units="second_order_rate_constant" public_interface="in" name="k11"/>
    <variable units="first_order_rate_constant" public_interface="in" name="k12"/>
    <variable units="second_order_rate_constant" public_interface="in" name="k15"/>
    <variable units="first_order_rate_constant" public_interface="in" name="k16"/>
    <variable units="millimolar" public_interface="in" name="E_"/>
    <variable units="millimolar" public_interface="in" name="ENaCl_"/>
    <variable units="millimolar" public_interface="in" name="Na_"/>
    <variable units="millimolar" public_interface="in" name="Cl_"/>
    <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> ECl_ </ci> 
        </apply>
        <apply>
          <minus/>
          <apply>
            <plus/> 
            <apply>
              <times/>
              <ci> k11 </ci>
              <ci> Cl_ </ci>
              <ci> E_ </ci>
            </apply>
            <apply>
              <times/>
              <ci> k16 </ci>
              <ci> ENaCl_ </ci>
            </apply>
          </apply>
          <apply>
            <plus/>
            <apply>
              <times/>  
              <ci> k15 </ci>
              <ci> Na_ </ci>
              <ci> ECl_ </ci> 
            </apply>
            <apply>
              <times/>  
              <ci> k12 </ci>
              <ci> ECl_ </ci>
            </apply>
          </apply>
        </apply>  
      </apply>  
    </math> 
  </component>
  
  <component name="ENaCl" cmeta:id="ENaCl">
     
    <variable units="millimolar" public_interface="out" name="ENaCl"/> 
    
    <variable units="second_order_rate_constant" public_interface="in" name="k7"/>
    <variable units="first_order_rate_constant" public_interface="in" name="k8"/>
    <variable units="second_order_rate_constant" public_interface="in" name="k5"/>
    <variable units="first_order_rate_constant" public_interface="in" name="k6"/>
    <variable units="first_order_rate_constant" public_interface="in" name="k19"/>
    <variable units="first_order_rate_constant" public_interface="in" name="k20"/>
    <variable units="millimolar" public_interface="in" name="ENa"/>
    <variable units="millimolar" public_interface="in" name="ECl"/>
    <variable units="millimolar" public_interface="in" name="ENaCl_"/>
    <variable units="millimolar" public_interface="in" name="Na"/>
    <variable units="millimolar" public_interface="in" name="Cl"/>
    <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> ENaCl </ci> 
        </apply>
        <apply>
          <minus/>
          <apply>
            <plus/> 
            <apply>
              <times/>
              <ci> k5 </ci>
              <ci> Cl </ci>
              <ci> ENa </ci>
            </apply>
            <apply>
              <times/>
              <ci> k7 </ci>
              <ci> Na </ci>
              <ci> ECl </ci>
            </apply>
            <apply>
              <times/>
              <ci> k20 </ci>
              <ci> ENaCl_ </ci>
            </apply>
          </apply>
          <apply>
            <plus/>
            <apply>
              <times/>  
              <ci> k6 </ci>
              <ci> ENaCl </ci> 
            </apply>
            <apply>
              <times/>  
              <ci> k8 </ci>
              <ci> ENaCl </ci>
            </apply>
            <apply>
              <times/>  
              <ci> k19 </ci>
              <ci> ENaCl </ci>
            </apply>
          </apply>
        </apply>  
      </apply>  
    </math> 
  </component>
  
  <component name="ENaCl_" cmeta:id="ENaCl_">
     
    <variable units="millimolar" public_interface="out" name="ENaCl_"/> 
    
    <variable units="second_order_rate_constant" public_interface="in" name="k15"/>
    <variable units="first_order_rate_constant" public_interface="in" name="k16"/>
    <variable units="second_order_rate_constant" public_interface="in" name="k13"/>
    <variable units="first_order_rate_constant" public_interface="in" name="k14"/>
    <variable units="first_order_rate_constant" public_interface="in" name="k19"/>
    <variable units="first_order_rate_constant" public_interface="in" name="k20"/>
    <variable units="millimolar" public_interface="in" name="ENa_"/>
    <variable units="millimolar" public_interface="in" name="ECl_"/>
    <variable units="millimolar" public_interface="in" name="ENaCl"/>
    <variable units="millimolar" public_interface="in" name="Na_"/>
    <variable units="millimolar" public_interface="in" name="Cl_"/>
    <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> ENaCl_ </ci> 
        </apply>
        <apply>
          <minus/>
          <apply>
            <plus/> 
            <apply>
              <times/>
              <ci> k13 </ci>
              <ci> Cl_ </ci>
              <ci> ENa_ </ci>
            </apply>
            <apply>
              <times/>
              <ci> k15 </ci>
              <ci> Na_ </ci>
              <ci> ECl_ </ci>
            </apply>
            <apply>
              <times/>
              <ci> k19 </ci>
              <ci> ENaCl </ci>
            </apply>
          </apply>
          <apply>
            <plus/>
            <apply>
              <times/>  
              <ci> k14 </ci>
              <ci> ENaCl_ </ci> 
            </apply>
            <apply>
              <times/>  
              <ci> k16 </ci>
              <ci> ENaCl_ </ci>
            </apply>
            <apply>
              <times/>  
              <ci> k20 </ci>
              <ci> ENaCl_ </ci>
            </apply>
          </apply>
        </apply>  
      </apply>  
    </math> 
  </component>
  
  <component name="reaction_constants">
    <variable units="second_order_rate_constant" public_interface="out" name="k1" initial_value="1.0E8"/>
    <variable units="first_order_rate_constant" public_interface="out" name="k2" initial_value="4.183E5"/>
    <variable units="second_order_rate_constant" public_interface="out" name="k3" initial_value="1.0E8"/>
    <variable units="first_order_rate_constant" public_interface="out" name="k4" initial_value="4.928E6"/>
    <variable units="second_order_rate_constant" public_interface="out" name="k5" initial_value="1.0E8"/>
    <variable units="first_order_rate_constant" public_interface="out" name="k6" initial_value="1.065E6"/>
    <variable units="second_order_rate_constant" public_interface="out" name="k7" initial_value="1.0E8"/>
    <variable units="first_order_rate_constant" public_interface="out" name="k8" initial_value="8.940E4"/>
    <variable units="second_order_rate_constant" public_interface="out" name="k9" initial_value="1.0E8"/>
    <variable units="first_order_rate_constant" public_interface="out" name="k10" initial_value="4.183E5"/>
    <variable units="second_order_rate_constant" public_interface="out" name="k11" initial_value="1.0E8"/>
    <variable units="first_order_rate_constant" public_interface="out" name="k12" initial_value="4.982E6"/>
    <variable units="second_order_rate_constant" public_interface="out" name="k13" initial_value="1.0E8"/>
    <variable units="first_order_rate_constant" public_interface="out" name="k14" initial_value="1.065E6"/>
    <variable units="second_order_rate_constant" public_interface="out" name="k15" initial_value="1.0E8"/>
    <variable units="first_order_rate_constant" public_interface="out" name="k16" initial_value="8.940E4"/>
    <variable units="first_order_rate_constant" public_interface="out" name="k17" initial_value="4.587E5"/>
    <variable units="first_order_rate_constant" public_interface="out" name="k18" initial_value="1.0E5"/>
    <variable units="first_order_rate_constant" public_interface="out" name="k19" initial_value="1.0E3"/>
    <variable units="first_order_rate_constant" public_interface="out" name="k20" initial_value="2.180E2"/>
    <variable units="second_order_rate_constant" public_interface="out" name="k21" initial_value="1.0E8"/>
    <variable units="first_order_rate_constant" public_interface="out" name="k22" initial_value="4.183E5"/>
    <variable units="second_order_rate_constant" public_interface="out" name="k23" initial_value="1.0E8"/>
    <variable units="first_order_rate_constant" public_interface="out" name="k24" initial_value="3.192E1"/>
    <variable units="second_order_rate_constant" public_interface="out" name="k25" initial_value="1.0E8"/>
    <variable units="first_order_rate_constant" public_interface="out" name="k26" initial_value="3.192E1"/>
    <variable units="second_order_rate_constant" public_interface="out" name="k27" initial_value="1.0E8"/>
    <variable units="first_order_rate_constant" public_interface="out" name="k28" initial_value="1.389E5"/>
    <variable units="second_order_rate_constant" public_interface="out" name="k29" initial_value="1.0E8"/>
    <variable units="first_order_rate_constant" public_interface="out" name="k30" initial_value="3.514E-1"/>
    <variable units="second_order_rate_constant" public_interface="out" name="k31" initial_value="1.0E8"/>
    <variable units="first_order_rate_constant" public_interface="out" name="k32" initial_value="1.166E-1"/>
    <variable units="millimolar" public_interface="out" name="Na" initial_value="50.0"/>
    <variable units="millimolar" public_interface="out" name="Cl" initial_value="96.0"/>
    <variable units="nanomolar" public_interface="out" name="D" initial_value="1.0"/>
    <variable units="millimolar" public_interface="out" name="Cl_" initial_value="40.0"/>
    <variable units="millimolar" public_interface="out" name="Na_" initial_value="10.0"/>
    <variable units="nanomolar" public_interface="out" name="D_" initial_value="1.0"/>
  </component>
  
  <connection>
     <map_components component_2="environment" component_1="E"/>
     <map_variables variable_2="time" variable_1="time"/>
  </connection>
  
  <connection>
     <map_components component_2="environment" component_1="E_"/>
     <map_variables variable_2="time" variable_1="time"/>
  </connection>
  
  <connection>
     <map_components component_2="environment" component_1="ENa"/>
     <map_variables variable_2="time" variable_1="time"/>
  </connection>
  
  <connection>
     <map_components component_2="environment" component_1="ENa_"/>
     <map_variables variable_2="time" variable_1="time"/>
  </connection>
  
  <connection>
     <map_components component_2="environment" component_1="ED"/>
     <map_variables variable_2="time" variable_1="time"/>
  </connection>
  
  <connection>
     <map_components component_2="environment" component_1="ED_"/>
     <map_variables variable_2="time" variable_1="time"/>
  </connection>
  
  <connection>
     <map_components component_2="environment" component_1="ECl"/>
     <map_variables variable_2="time" variable_1="time"/>
  </connection>
  
  <connection>
     <map_components component_2="environment" component_1="ECl_"/>
     <map_variables variable_2="time" variable_1="time"/>
  </connection>
  
  <connection>
     <map_components component_2="environment" component_1="ENaD"/>
     <map_variables variable_2="time" variable_1="time"/>
  </connection>
  
  <connection>
     <map_components component_2="environment" component_1="ENaD_"/>
     <map_variables variable_2="time" variable_1="time"/>
  </connection>
  
  <connection>
     <map_components component_2="environment" component_1="ENaCl"/>
     <map_variables variable_2="time" variable_1="time"/>
  </connection>
  
  <connection>
     <map_components component_2="environment" component_1="ENaCl_"/>
     <map_variables variable_2="time" variable_1="time"/>
  </connection>
  
  <connection>
     <map_components component_2="ED" component_1="E"/>
     <map_variables variable_2="E" variable_1="E"/>
     <map_variables variable_2="ED" variable_1="ED"/>
  </connection>

  <connection>
     <map_components component_2="ED_" component_1="E_"/>
     <map_variables variable_2="E_" variable_1="E_"/>
     <map_variables variable_2="ED_" variable_1="ED_"/>
  </connection>

  <connection>
     <map_components component_2="ENa" component_1="E"/>
     <map_variables variable_2="E" variable_1="E"/>
     <map_variables variable_2="ENa" variable_1="ENa"/>
  </connection>

  <connection>
     <map_components component_2="ENa_" component_1="E_"/>
     <map_variables variable_2="E_" variable_1="E_"/>
     <map_variables variable_2="ENa_" variable_1="ENa_"/>
  </connection>
  
  <connection>
     <map_components component_2="ECl" component_1="E"/>
     <map_variables variable_2="E" variable_1="E"/>
     <map_variables variable_2="ECl" variable_1="ECl"/>
  </connection>

  <connection>
     <map_components component_2="ECl_" component_1="E_"/>
     <map_variables variable_2="E_" variable_1="E_"/>
     <map_variables variable_2="ECl_" variable_1="ECl_"/>
  </connection>

  <connection>
     <map_components component_2="E_" component_1="E"/>
     <map_variables variable_2="E" variable_1="E"/>
     <map_variables variable_2="E_" variable_1="E_"/>
  </connection>

  <connection>
     <map_components component_2="ED" component_1="ENaD"/>
     <map_variables variable_2="ENaD" variable_1="ENaD"/>
     <map_variables variable_2="ED" variable_1="ED"/>
  </connection>

  <connection>
     <map_components component_2="ED_" component_1="ENaD_"/>
     <map_variables variable_2="ENaD_" variable_1="ENaD_"/>
     <map_variables variable_2="ED_" variable_1="ED_"/>
  </connection>

  <connection>
     <map_components component_2="ENa" component_1="ENaD"/>
     <map_variables variable_2="ENaD" variable_1="ENaD"/>
     <map_variables variable_2="ENa" variable_1="ENa"/>
  </connection>

  <connection>
     <map_components component_2="ENa_" component_1="ENaD_"/>
     <map_variables variable_2="ENaD_" variable_1="ENaD_"/>
     <map_variables variable_2="ENa_" variable_1="ENa_"/>
  </connection>

  <connection>
     <map_components component_2="ENa" component_1="ENaCl"/>
     <map_variables variable_2="ENaCl" variable_1="ENaCl"/>
     <map_variables variable_2="ENa" variable_1="ENa"/>
  </connection>

  <connection>
     <map_components component_2="ENa_" component_1="ENaCl_"/>
     <map_variables variable_2="ENaCl_" variable_1="ENaCl_"/>
     <map_variables variable_2="ENa_" variable_1="ENa_"/>
  </connection>

  <connection>
     <map_components component_2="ECl" component_1="ENaCl"/>
     <map_variables variable_2="ENaCl" variable_1="ENaCl"/>
     <map_variables variable_2="ECl" variable_1="ECl"/>
  </connection>

  <connection>
     <map_components component_2="ECl_" component_1="ENaCl_"/>
     <map_variables variable_2="ENaCl_" variable_1="ENaCl"/>
     <map_variables variable_2="ECl_" variable_1="ECl_"/>
  </connection>

  <connection>
     <map_components component_2="ENaCl" component_1="ENaCl_"/>
     <map_variables variable_2="ENaCl_" variable_1="ENaCl_"/>
     <map_variables variable_2="ENaCl" variable_1="ENaCl"/>
  </connection>
  
  <connection>
    <map_components component_2="reaction_constants" component_1="E"/>
    <map_variables variable_2="k23" variable_1="k23"/>
    <map_variables variable_2="k24" variable_1="k24"/>
    <map_variables variable_2="k1" variable_1="k1"/>
    <map_variables variable_2="k2" variable_1="k2"/>
    <map_variables variable_2="k3" variable_1="k3"/>
    <map_variables variable_2="k4" variable_1="k4"/>
    <map_variables variable_2="k17" variable_1="k17"/>
    <map_variables variable_2="k18" variable_1="k18"/>
    <map_variables variable_2="Cl" variable_1="Cl"/>
    <map_variables variable_2="Na" variable_1="Na"/>
    <map_variables variable_2="D" variable_1="D"/>
  </connection>

  <connection>
    <map_components component_2="reaction_constants" component_1="ED"/>
    <map_variables variable_2="k23" variable_1="k23"/>
    <map_variables variable_2="k24" variable_1="k24"/>
    <map_variables variable_2="k21" variable_1="k21"/>
    <map_variables variable_2="k22" variable_1="k22"/>
    <map_variables variable_2="D" variable_1="D"/>
    <map_variables variable_2="Na" variable_1="Na"/>
  </connection>

  <connection>
    <map_components component_2="reaction_constants" component_1="ENaD"/>
    <map_variables variable_2="k21" variable_1="k21"/>
    <map_variables variable_2="k22" variable_1="k22"/>
    <map_variables variable_2="k25" variable_1="k25"/>
    <map_variables variable_2="k26" variable_1="k26"/>
    <map_variables variable_2="Na" variable_1="Na"/>
    <map_variables variable_2="D" variable_1="D"/>
  </connection>

  <connection>
    <map_components component_2="reaction_constants" component_1="ENa"/>
    <map_variables variable_2="k25" variable_1="k25"/>
    <map_variables variable_2="k26" variable_1="k26"/>
    <map_variables variable_2="k1" variable_1="k1"/>
    <map_variables variable_2="k2" variable_1="k2"/>
    <map_variables variable_2="k5" variable_1="k5"/>
    <map_variables variable_2="k6" variable_1="k6"/>
    <map_variables variable_2="Cl" variable_1="Cl"/>
    <map_variables variable_2="Na" variable_1="Na"/>
    <map_variables variable_2="D" variable_1="D"/>
  </connection>

  <connection>
    <map_components component_2="reaction_constants" component_1="ECl"/>
    <map_variables variable_2="k7" variable_1="k7"/>
    <map_variables variable_2="k8" variable_1="k8"/>
    <map_variables variable_2="k3" variable_1="k3"/>
    <map_variables variable_2="k4" variable_1="k4"/>
    <map_variables variable_2="Cl" variable_1="Cl"/>
    <map_variables variable_2="Na" variable_1="Na"/>
  </connection>

  <connection>
    <map_components component_2="reaction_constants" component_1="ENaCl"/>
    <map_variables variable_2="k7" variable_1="k7"/>
    <map_variables variable_2="k8" variable_1="k8"/>
    <map_variables variable_2="k5" variable_1="k5"/>
    <map_variables variable_2="k6" variable_1="k6"/>
    <map_variables variable_2="k19" variable_1="k19"/>
    <map_variables variable_2="k20" variable_1="k20"/>
    <map_variables variable_2="Cl" variable_1="Cl"/>
    <map_variables variable_2="Na" variable_1="Na"/>
  </connection>

  <connection>
    <map_components component_2="reaction_constants" component_1="E_"/>
    <map_variables variable_2="k29" variable_1="k29"/>
    <map_variables variable_2="k30" variable_1="k30"/>
    <map_variables variable_2="k11" variable_1="k11"/>
    <map_variables variable_2="k12" variable_1="k12"/>
    <map_variables variable_2="k9" variable_1="k9"/>
    <map_variables variable_2="k10" variable_1="k10"/>
    <map_variables variable_2="k17" variable_1="k17"/>
    <map_variables variable_2="k18" variable_1="k18"/>
    <map_variables variable_2="Cl_" variable_1="Cl_"/>
    <map_variables variable_2="Na_" variable_1="Na_"/>
    <map_variables variable_2="D_" variable_1="D_"/>
  </connection>

  <connection>
    <map_components component_2="reaction_constants" component_1="ED_"/>
    <map_variables variable_2="k29" variable_1="k29"/>
    <map_variables variable_2="k30" variable_1="k30"/>
    <map_variables variable_2="k27" variable_1="k27"/>
    <map_variables variable_2="k27" variable_1="k28"/>
    <map_variables variable_2="D_" variable_1="D_"/>
    <map_variables variable_2="Na_" variable_1="Na_"/>
  </connection>

  <connection>
    <map_components component_2="reaction_constants" component_1="ENaD_"/>
    <map_variables variable_2="k27" variable_1="k27"/>
    <map_variables variable_2="k28" variable_1="k28"/>
    <map_variables variable_2="k31" variable_1="k31"/>
    <map_variables variable_2="k32" variable_1="k32"/>
    <map_variables variable_2="Na_" variable_1="Na_"/>
    <map_variables variable_2="D_" variable_1="D_"/>
  </connection>

  <connection>
    <map_components component_2="reaction_constants" component_1="ENa_"/>
    <map_variables variable_2="k31" variable_1="k31"/>
    <map_variables variable_2="k32" variable_1="k32"/>
    <map_variables variable_2="k9" variable_1="k9"/>
    <map_variables variable_2="k10" variable_1="k10"/>
    <map_variables variable_2="k13" variable_1="k13"/>
    <map_variables variable_2="k14" variable_1="k14"/>
    <map_variables variable_2="Cl_" variable_1="Cl_"/>
    <map_variables variable_2="Na_" variable_1="Na_"/>
    <map_variables variable_2="D_" variable_1="D_"/>
  </connection>

  <connection>
    <map_components component_2="reaction_constants" component_1="ECl_"/>
    <map_variables variable_2="k11" variable_1="k11"/>
    <map_variables variable_2="k12" variable_1="k12"/>
    <map_variables variable_2="k15" variable_1="k15"/>
    <map_variables variable_2="k16" variable_1="k16"/>
    <map_variables variable_2="Cl_" variable_1="Cl_"/>
    <map_variables variable_2="Na_" variable_1="Na_"/>
  </connection>

  <connection>
    <map_components component_2="reaction_constants" component_1="ENaCl_"/>
    <map_variables variable_2="k15" variable_1="k15"/>
    <map_variables variable_2="k16" variable_1="k16"/>
    <map_variables variable_2="k13" variable_1="k13"/>
    <map_variables variable_2="k14" variable_1="k14"/>
    <map_variables variable_2="k19" variable_1="k19"/>
    <map_variables variable_2="k20" variable_1="k20"/>
    <map_variables variable_2="Cl_" variable_1="Cl_"/>
    <map_variables variable_2="Na_" variable_1="Na_"/>
  </connection>




<rdf:RDF>
  <rdf:Bag rdf:about="rdf:#0bb854d1-3425-4cba-92ed-6908aff6b72f">
    <rdf:li>kidney</rdf:li>
    <rdf:li>electrophysiology</rdf:li>
  </rdf:Bag>
  <rdf:Seq rdf:about="rdf:#327461b8-2a5f-48fd-baa2-a1b0bfa03aa1">
    <rdf:li rdf:resource="rdf:#3c05e2a2-0758-4b6a-ba9e-e7b56daf1cfc"/>
    <rdf:li rdf:resource="rdf:#91d96927-3af0-44cd-b73c-5a2f39ac25f8"/>
  </rdf:Seq>
  <rdf:Description rdf:about="/ENaCl_i">
    <dcterms:alternative>
          Intracellular Transporter-Sodium-Chloride Complex
        </dcterms:alternative>
    <dc:title>ENaCl_i</dc:title>
  </rdf:Description>
  <rdf:Description rdf:about="">
    <dc:publisher>The University of Auckland, Bioengineering Institute</dc:publisher>
    <cmeta:comment rdf:resource="rdf:#c757deb0-f55b-4c45-b2b0-83e8cbb36b30"/>
    <dcterms:created rdf:resource="rdf:#7d344280-89c4-476a-9759-2defb83ca1cb"/>
    <dc:creator rdf:resource="rdf:#55f6976c-a732-491e-a33b-43921256764c"/>
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    <dcterms:alternative>Extracellular Transporter</dcterms:alternative>
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    <vCard:Given/>
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  <rdf:Description rdf:about="/E_">
    <dcterms:alternative>Intracellular Transporter</dcterms:alternative>
    <dc:title>E_</dc:title>
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  <rdf:Description rdf:about="rdf:#29c527b6-239c-48ff-85da-34ac26662c99">
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  <rdf:Description rdf:about="/ED">
    <dcterms:alternative>
          Extracellular Transporter-Thiazide Diuretics Complex
        </dcterms:alternative>
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  <rdf:Description rdf:about="rdf:#37ac1892-aab1-45e8-9c2a-0b3560d86e09">
    <vCard:Given>Hangil</vCard:Given>
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    <dcterms:alternative>
          Intracellular Transporter-Sodium Complex
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    <dcterms:alternative>
          Extracellular Transporter-Sodium-Chloride Complex
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    <dcterms:W3CDTF>2007-06-05T09:16:58+12:00</dcterms:W3CDTF>
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    <dcterms:W3CDTF>2007-06-25T13:20:00+12:00</dcterms:W3CDTF>
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    <vCard:Given>Catherine</vCard:Given>
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          Extracellular Transporter-Chloride Complex
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    <rdf:value>This is the CellML description of Chang and Fujita's 1999 kinetic model of the thiazide-sensitive Na-Cl cotransporter of the renal distal tubule.&#13;
&#13;
This model can be run in PCEnv but it gives a flat output.  I suspect it needs to be embedded within a whole cell model in order to give a reasonable output.</rdf:value>
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    <vCard:Orgname>The University of Auckland</vCard:Orgname>
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       Chang and Fujita's 1999 kinetic model of the thiazide-sensitive Na-Cl cotransporter of the renal distal tubule.
      </dc:title>
    <cmeta:bio_entity>Renal Distal Tubule</cmeta:bio_entity>
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    <dcterms:alternative>
          Intracellular Transporter-Chloride Complex
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  <rdf:Description rdf:about="rdf:#cd2c94aa-dae0-4b2c-be83-be425f1ac5cc">
    <vCard:FN>Catherine Lloyd</vCard:FN>
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    <dc:title>American Journal of Physiology</dc:title>
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          Extracellular Transporter-Sodium Complex
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    <vCard:Given>Catherine</vCard:Given>
    <vCard:Family>Lloyd</vCard:Family>
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    <rdf:value>The new version of this model has been re-coded to remove the reaction element and replace it with a simple MathML description of the model reaction kinetics.  This is thought to be truer to the original publication, and information regarding the enzyme kinetics etc will later be added to the metadata through use of an ontology.&#13;
&#13;
The model runs in the PCEnv simulator but gives a flat output.</rdf:value>
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  <rdf:Description rdf:about="/ED_">
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          Intracellular Transporter-Thiazide Diuretics Complex
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    <dc:title>ED_</dc:title>
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  <rdf:Description rdf:about="/ENaD">
    <dcterms:alternative>
          Extracellular Transporter-Thiazide Diuretics-Sodium Complex
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  <rdf:Description rdf:about="rdf:#c757deb0-f55b-4c45-b2b0-83e8cbb36b30">
    <dc:creator rdf:resource="rdf:#cd2c94aa-dae0-4b2c-be83-be425f1ac5cc"/>
    <rdf:value>The new version of this model has been re-coded to remove the reaction element and replace it with a simple MathML description of the model reaction kinetics.  This is thought to be truer to the original publication, and information regarding the enzyme kinetics etc will later be added to the metadata through use of an ontology.&#13;
&#13;
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    <rdf:type rdf:resource="http://imc.org/vCard/3.0#internet"/>
    <rdf:value>c.lloyd@auckland.ac.nz</rdf:value>
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    <bqs:Pubmed_id>10362783</bqs:Pubmed_id>
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    <vCard:Given>Toshiro</vCard:Given>
    <vCard:Family>Fujita</vCard:Family>
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    <vCard:N rdf:resource="rdf:#297d5548-8c46-4515-b053-80d681025204"/>
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  <rdf:Description rdf:about="/ENaD_">
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          Intracellular Transporter-Thiazide Diuretics-Sodium Complex
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    <dc:title>ENaD_</dc:title>
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    <rdf:value>Removed reaction element and replaced with simple MathML</rdf:value>
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    <dcterms:W3CDTF>1999-06</dcterms:W3CDTF>
  </rdf:Description>
  <rdf:Description rdf:about="rdf:#7d344280-89c4-476a-9759-2defb83ca1cb">
    <dcterms:W3CDTF>2007-05-28T00:00:00+00:00</dcterms:W3CDTF>
  </rdf:Description>
  <rdf:Description rdf:about="rdf:#077e8ed7-4af5-45d7-a2c9-2ce274da2919">
    <dc:creator rdf:resource="rdf:#327461b8-2a5f-48fd-baa2-a1b0bfa03aa1"/>
    <dc:title>A kinetic model of the thiazide-sensitive Na-Cl cotransporter</dc:title>
    <bqs:volume>276</bqs:volume>
    <bqs:first_page>F952</bqs:first_page>
    <bqs:Journal rdf:resource="rdf:#9e0eecbc-2c2a-4d42-8b75-6ba6c1bc718a"/>
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    <bqs:last_page>F959</bqs:last_page>
  </rdf:Description>
  <rdf:Description rdf:about="rdf:#8c884d73-01b7-4eeb-9206-ac93b3d6c7e6">
    <vCard:FN>Catherine Lloyd</vCard:FN>
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