Rendering of the source text

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<!--  FILE :  weinstein_1998_gastric_H_K_ATPase_model_version02.xml

CREATED :  25th May 2007

LAST MODIFIED : 25th 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 Alan Weinstein's 1998 mathematical model of the inner medullary collecting duct of the rat: acid/base transport.

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:pathway_editor="http://www.physiome.com/pathway_editor/1.0#" xmlns:vCard="http://www.w3.org/2001/vcard-rdf/3.0#" cmeta:id="weinstein_1998_gastric_H_K_ATPase_model" name="weinstein_1998_version02">
<documentation xmlns="http://cellml.org/tmp-documentation">
<article>
  <articleinfo>
  <title>Acid/base Transport in the Inner Medullary Collecting Duct of the Rat</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 CellML model variant describes the gastric H+/K+ ATPase.</para>
      </section>
      <sect1 id="sec_structure">
<title>Model Structure</title>

<para>
ABSTRACT: A mathematical model of the inner medullary collecting duct (IMCD) of the rat has been developed that is suitable for simulating luminal buffer titration and ammonia secretion by this nephron segment. Luminal proton secretion has been assigned to an H-K-ATPase, which has been represented by adapting the kinetic model of the gastric enzyme by Brzezinski et al. (P. Brzezinski, B. G. Malmstrom, P. Lorentzon, and B. Wallmark. Biochim. Biophys. Acta 942: 215-219, 1988). In shifting to a 2 H+:1 ATP stoichiometry, the model enzyme can acidify the tubule lumen approximately 3 pH units below that of the cytosol, when luminal K+ is in abundance. Peritubular base exit is a combination of ammonia recycling and HCO3- flux (either via Cl-/HCO3- exchange or via a Cl- channel). Ammonia recycling involves NH4(+) uptake on the Na-K-ATPase followed by diffusive NH3 exit [S. M. Wall. Am. J. Physiol. 270 (Renal Physiol. 39): F432-F439, 1996]; model calculations suggest that this is the principal mode of base exit. By virtue of this mechanism, the model also suggests that realistic elevations in peritubular K+ concentration will compromise IMCD acid secretion. Although ammonia recycling is insensitive to carbonic anhydrase (CA) inhibition, the base exit linked to HCO3- flux provides a CA-sensitive component to acid secretion. In model simulations, it is observed that increased luminal NaCl entry increases ammonia cycling but decreases peritubular Cl-/HCO3- exchange (due to increased cell Cl-). This parallel system of peritubular base exit stabilizes acid secretion in the face of variable Na+ reabsorption.</para>

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

<para>
A mathematical model of the inner medullary collecting duct of the rat: acid/base transport, Alan M. Weinstein, 1998, 
            <emphasis>American Journal of Physiology</emphasis>, 274(5 Pt 2), F856-67. <ulink url="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&amp;db=PubMed&amp;list_uids=6496750&amp;dopt=Abstract">PubMed ID: 6496750</ulink> 
</para>

<informalfigure float="0" id="fig_pathway_rendering">
<mediaobject>
  <imageobject>
    <objectinfo>
      <title>pathway_rendering</title>
    </objectinfo>
    <imagedata fileref="weinstein_1998a.png"/>
  </imageobject>
</mediaobject>
<caption>Conventional rendering of the gastric H-K-ATPase model.  This model has a stoichiometry of two H<superscript>+</superscript> and two K<superscript>+</superscript> per ATP.  E<subscript>1</subscript> and E<subscript>2</subscript> are the cytosolic- and luminal-facing enzymes, respectively.</caption>
</informalfigure>

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


  
  
  
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              <ci> k11 </ci>
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    <variable units="millimolar" public_interface="out" name="ATP" initial_value="2.0"/>
    <variable units="millimolar" public_interface="out" name="ADP" initial_value="0.04"/>
    <variable units="second_order_rate_constant" public_interface="out" name="k1" initial_value="1.3E7"/>
    <variable units="first_order_rate_constant" public_interface="out" name="k1_" initial_value="6.5"/>
    <variable units="first_order_rate_constant" public_interface="out" name="k2" initial_value="4E3"/>
    <variable units="second_order_rate_constant" public_interface="out" name="k2_" initial_value="4E4"/>
    <variable units="second_order_rate_constant" public_interface="out" name="k3" initial_value="1.3E9"/>
    <variable units="first_order_rate_constant" public_interface="out" name="k3_" initial_value="5E2"/>
    <variable units="first_order_rate_constant" public_interface="out" name="k4" initial_value="5E1"/>
    <variable units="second_order_rate_constant" public_interface="out" name="k4_" initial_value="2.5E6"/>
    <variable units="first_order_rate_constant" public_interface="out" name="k5" initial_value="4E1"/>
    <variable units="first_order_rate_constant" public_interface="out" name="k5_" initial_value="2E2"/>
    <variable units="first_order_rate_constant" public_interface="out" name="k6" initial_value="5E7"/>
    <variable units="second_order_rate_constant" public_interface="out" name="k6_" initial_value="5E10"/>
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    <variable units="first_order_rate_constant" public_interface="out" name="k11_" initial_value="5E0"/>
  </component>  
  
  
  <connection>
    <map_components component_2="environment" component_1="K_E1"/>
    <map_variables variable_2="time" variable_1="time"/>
  </connection>

  <connection>
    <map_components component_2="environment" component_1="K_E1_ATP"/>
    <map_variables variable_2="time" variable_1="time"/>
  </connection>

  <connection>
    <map_components component_2="environment" component_1="E1_ATP"/>
    <map_variables variable_2="time" variable_1="time"/>
  </connection>

  <connection>
    <map_components component_2="environment" component_1="H_E1_ATP"/>
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  <connection>
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  </connection>

  <connection>
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    <map_variables variable_2="time" variable_1="time"/>
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  <connection>
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    <map_variables variable_2="time" variable_1="time"/>
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  <connection>
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    <map_variables variable_2="time" variable_1="time"/>
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  <connection>
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  <connection>
    <map_components component_2="environment" component_1="K_E2_ATP"/>
    <map_variables variable_2="time" variable_1="time"/>
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  <connection>
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  <connection>
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    <map_variables variable_2="E1_ATP" variable_1="E1_ATP"/>
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  <connection>
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    <map_components component_2="H_E1_ATP" component_1="E1_ATP"/>
    <map_variables variable_2="E1_ATP" variable_1="E1_ATP"/>
    <map_variables variable_2="H_E1_ATP" variable_1="H_E1_ATP"/>
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  <connection>
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  <connection>
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    <map_variables variable_2="K_E2_ATP" variable_1="K_E2_ATP"/>
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  <connection>
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    <map_variables variable_2="k9_" variable_1="k9_"/>
    <map_variables variable_2="k1" variable_1="k1"/>
    <map_variables variable_2="k1_" variable_1="k1_"/>
    <map_variables variable_2="ATP" variable_1="ATP"/>
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  <connection>
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  <connection>
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    <map_variables variable_2="k3" variable_1="k3"/>
    <map_variables variable_2="k3_" variable_1="k3_"/>
    <map_variables variable_2="K" variable_1="K"/>
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  <connection>
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  <connection>
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  <connection>
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  <connection>
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  <connection>
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    <map_variables variable_2="k11_" variable_1="k11_"/>
    <map_variables variable_2="ATP" variable_1="ATP"/>
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<rdf:RDF>
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    <dc:title>A mathematical model of the inner medullary collecting duct of the rat: acid/base transport (Gastric H+/K+ ATPase Variant)</dc:title>
	<dc:publisher>The University of Auckland, Bioengineering Institute</dc:publisher>
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    <vCard:Other>May</vCard:Other>
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    <bqs:first_page>F856</bqs:first_page>
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    <dc:title>
        The 1998 Weinstein mathematical model of the gastric H-K-ATPase.
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    <cmeta:bio_entity>Parietal Cell</cmeta:bio_entity>
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    <dcterms:W3CDTF>2007-06-05T09:27:29+12:00</dcterms:W3CDTF>
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    <dcterms:modified rdf:resource="rdf:#e93b27ca-9c2f-44a9-823c-08be568688e1"/>
    <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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