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A numerical model of acid-base transport in rat distal tubule
The CellML code.
<!-- FILE : renal_H_ATPase_model.xml
CREATED : 29th May 2007
LAST MODIFIED : 29th 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 2001 mathematical model of a H-ATPase in the distal tubule of the rat: it is one component of an overall model of acid/base transport in a distal tubule.
CHANGES:
-->
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<documentation xmlns="http://cellml.org/tmp-documentation">
<article>
<articleinfo>
<title>Mathematical Models of Ionic Transport in the Distal Tubule of the Rat</title>
<author>
<firstname>Catherine</firstname>
<surname>Lloyd</surname>
<affiliation>
<shortaffil>Bioengineering Institute, University of Auckland</shortaffil>
</affiliation>
</author>
</articleinfo>
<sect1 id="sec_structure">
<title>Model Structure</title>
<para>
Acid-base transport in the rat distal tubule of the kidney has been extensively studied by a variety of different experimental methods. These experiments have shown that in the early part of the distal tubule, H<superscript>+</superscript> is secreted into the tubular fluid via a Na/H exchanger embedded in the luminal membrane (see <xref linkend="fig_reaction_diagram1" /> below). Closely linked with this process is the transport of HCO<subscript>3</subscript>
<superscript>-</superscript> out of the cytosolic space into the basolateral space. This probably occurs via an anion exchanger (see <xref linkend="fig_reaction_diagram2" /> below). In the late distal tubule, distinct cell types called intercalated cells are present. These cells are specifically involved in acid-base transport. Type A cells secrete H<superscript>+</superscript> via a luminal H-ATPase (see <xref linkend="fig_reaction_diagram3" /> and <xref linkend="fig_reaction_diagram4" /> below), and they extrude HCO<subscript>3</subscript>
<superscript>-</superscript> via a basolateral anion exchanger. Type B cells have anion transporters on their opposite side, and they function to secrete HCO<subscript>3</subscript>
<superscript>-</superscript> into the tubular fluid.
</para>
<para>
The features of acid-base transport described above are captured in the mathematical models of Hangil Chang and Toshiro Fujita (2001). Their models of transporters simulate the transport kinetics of the Na/H exchanger, anion exchanger and the H-ATPase. The raw CellML descriptions of the models 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://ajprenal.physiology.org/cgi/content/abstract/281/2/F222">A numerical model of acid-base transport in rat distal tubule</ulink>, Hangil Chang and Toshiro Fujita, 2001, <ulink url="http://ajpcon.physiology.org/">
<emphasis>American Journal of Physiology</emphasis>
</ulink>, 281, F222-F243. (<ulink url="http://ajprenal.physiology.org/cgi/reprint/281/2/F222.pdf">PDF</ulink> and <ulink url="http://ajprenal.physiology.org/cgi/content/full/281/2/F222">text</ulink> versions of the article are available to Journal subscribers. <ulink url="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=11457714&dopt=Abstract">PubMed ID: 11457714</ulink>)
</para>
<informalfigure float="0" id="fig_reaction_diagram1">
<mediaobject>
<imageobject>
<objectinfo>
<title>reaction_diagram1</title>
</objectinfo>
<imagedata fileref="../images/renal_ionic_transport_model/Na_H_reaction_diagram.gif" />
</imageobject>
</mediaobject>
<caption>State diagram of the Na-H exchanger. In this model, the Na-H exchanger has a single binding site (E) to which Na<superscript>+</superscript>, H<superscript>+</superscript>, and NH<subscript>4</subscript>
<superscript>+</superscript> bind competitively. Only the bound forms of the transporter are able to cross the membrane. (Symbols with the asterisk (*) represent conformations facing the cytosol, symbols without indicate conformations facing the extracellular environment.)</caption>
</informalfigure>
<informalfigure float="0" id="fig_reaction_diagram2">
<mediaobject>
<imageobject>
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<title>reaction_diagram2</title>
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<imagedata fileref="../images/renal_ionic_transport_model/anion_exchanger_reaction_diagram.gif" />
</imageobject>
</mediaobject>
<caption>State diagram of the anion exchanger. In this model, the anion transporter (E) has a single binding site to which Cl<superscript>-</superscript> and HCO<subscript>3</subscript>
<superscript>-</superscript> competitively bind. Only the bound forms of the transporter are able to cross the membrane. (Symbols with the asterisk (*) represent conformations facing the cytosol, symbols without indicate conformations facing the extracellular environment.)</caption>
</informalfigure>
<informalfigure float="0" id="fig_reaction_diagram3">
<mediaobject>
<imageobject>
<objectinfo>
<title>reaction_diagram3</title>
</objectinfo>
<imagedata fileref="../images/renal_ionic_transport_model/H_ATPase_diagram.gif" />
</imageobject>
</mediaobject>
<caption>Conceptual diagram of the H-ATPase. The transporter consists of two components: a transmembrane channel and an intracellular catalytic unit. Between these two components there is a buffer space known as the antechamber, in which hydrogen ions (H<subscript>a</subscript>) are in equilibrium with extracellular hydrogen ions (H) due to a large conductance of the transmembrane channel. Hydrogen ions are also moved between the antechamber and the cytosol via the catalytic unit. This ion transport is coupled to ATP hydrolysis/synthesis.</caption>
</informalfigure>
<informalfigure float="0" id="fig_reaction_diagram4">
<mediaobject>
<imageobject>
<objectinfo>
<title>reaction_diagram4</title>
</objectinfo>
<imagedata fileref="../images/renal_ionic_transport_model/H_ATPase_reaction_diagram.gif" />
</imageobject>
</mediaobject>
<caption>State diagram of the catalytic unit of the H-ATPase. The catalytic unit (E) has two binding sites for H. Symbols with the asterisk (*) indicate conformations of the catalytic unit in which the binding sites face the cytosol, and symbols without the asterisk represent conformations in which the binding sites face the antechamber. Transition between the unloaded conformations is coupled with ATP synthesis/hydrolysis.</caption>
</informalfigure>
</sect1>
</article>
</documentation>
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CREATED : 29th May 2007
LAST MODIFIED : 29th 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 2001 mathematical model of a H-ATPase in the distal tubule of the rat: it is one component of an overall model of acid/base transport in a distal tubule.
CHANGES:
-->
<model xmlns:vCard="http://www.w3.org/2001/vcard-rdf/3.0#" xmlns:dcterms="http://purl.org/dc/terms/" xmlns:cellml="http://www.cellml.org/cellml/1.0#" xmlns:bqs="http://www.cellml.org/bqs/1.0#" xmlns:rdf="http://www.w3.org/1999/02/22-rdf-syntax-ns#" xmlns:dc="http://purl.org/dc/elements/1.1/" xmlns:cmeta="http://www.cellml.org/metadata/1.0#" xmlns="http://www.cellml.org/cellml/1.0#" cmeta:id="renal_H_ATPase_model" name="chang_fujita_2001_version03">
<documentation xmlns="http://cellml.org/tmp-documentation">
<article>
<articleinfo>
<title>Mathematical Models of Ionic Transport in the Distal Tubule of the Rat</title>
<author>
<firstname>Catherine</firstname>
<surname>Lloyd</surname>
<affiliation>
<shortaffil>Bioengineering Institute, University of Auckland</shortaffil>
</affiliation>
</author>
</articleinfo>
<sect1 id="sec_structure">
<title>Model Structure</title>
<para>
Acid-base transport in the rat distal tubule of the kidney has been extensively studied by a variety of different experimental methods. These experiments have shown that in the early part of the distal tubule, H<superscript>+</superscript> is secreted into the tubular fluid via a Na/H exchanger embedded in the luminal membrane (see <xref linkend="fig_reaction_diagram1" /> below). Closely linked with this process is the transport of HCO<subscript>3</subscript>
<superscript>-</superscript> out of the cytosolic space into the basolateral space. This probably occurs via an anion exchanger (see <xref linkend="fig_reaction_diagram2" /> below). In the late distal tubule, distinct cell types called intercalated cells are present. These cells are specifically involved in acid-base transport. Type A cells secrete H<superscript>+</superscript> via a luminal H-ATPase (see <xref linkend="fig_reaction_diagram3" /> and <xref linkend="fig_reaction_diagram4" /> below), and they extrude HCO<subscript>3</subscript>
<superscript>-</superscript> via a basolateral anion exchanger. Type B cells have anion transporters on their opposite side, and they function to secrete HCO<subscript>3</subscript>
<superscript>-</superscript> into the tubular fluid.
</para>
<para>
The features of acid-base transport described above are captured in the mathematical models of Hangil Chang and Toshiro Fujita (2001). Their models of transporters simulate the transport kinetics of the Na/H exchanger, anion exchanger and the H-ATPase. The raw CellML descriptions of the models 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://ajprenal.physiology.org/cgi/content/abstract/281/2/F222">A numerical model of acid-base transport in rat distal tubule</ulink>, Hangil Chang and Toshiro Fujita, 2001, <ulink url="http://ajpcon.physiology.org/">
<emphasis>American Journal of Physiology</emphasis>
</ulink>, 281, F222-F243. (<ulink url="http://ajprenal.physiology.org/cgi/reprint/281/2/F222.pdf">PDF</ulink> and <ulink url="http://ajprenal.physiology.org/cgi/content/full/281/2/F222">text</ulink> versions of the article are available to Journal subscribers. <ulink url="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=11457714&dopt=Abstract">PubMed ID: 11457714</ulink>)
</para>
<informalfigure float="0" id="fig_reaction_diagram1">
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<title>reaction_diagram1</title>
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<imagedata fileref="../images/renal_ionic_transport_model/Na_H_reaction_diagram.gif" />
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<caption>State diagram of the Na-H exchanger. In this model, the Na-H exchanger has a single binding site (E) to which Na<superscript>+</superscript>, H<superscript>+</superscript>, and NH<subscript>4</subscript>
<superscript>+</superscript> bind competitively. Only the bound forms of the transporter are able to cross the membrane. (Symbols with the asterisk (*) represent conformations facing the cytosol, symbols without indicate conformations facing the extracellular environment.)</caption>
</informalfigure>
<informalfigure float="0" id="fig_reaction_diagram2">
<mediaobject>
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<imagedata fileref="../images/renal_ionic_transport_model/anion_exchanger_reaction_diagram.gif" />
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</mediaobject>
<caption>State diagram of the anion exchanger. In this model, the anion transporter (E) has a single binding site to which Cl<superscript>-</superscript> and HCO<subscript>3</subscript>
<superscript>-</superscript> competitively bind. Only the bound forms of the transporter are able to cross the membrane. (Symbols with the asterisk (*) represent conformations facing the cytosol, symbols without indicate conformations facing the extracellular environment.)</caption>
</informalfigure>
<informalfigure float="0" id="fig_reaction_diagram3">
<mediaobject>
<imageobject>
<objectinfo>
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<imagedata fileref="../images/renal_ionic_transport_model/H_ATPase_diagram.gif" />
</imageobject>
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<caption>Conceptual diagram of the H-ATPase. The transporter consists of two components: a transmembrane channel and an intracellular catalytic unit. Between these two components there is a buffer space known as the antechamber, in which hydrogen ions (H<subscript>a</subscript>) are in equilibrium with extracellular hydrogen ions (H) due to a large conductance of the transmembrane channel. Hydrogen ions are also moved between the antechamber and the cytosol via the catalytic unit. This ion transport is coupled to ATP hydrolysis/synthesis.</caption>
</informalfigure>
<informalfigure float="0" id="fig_reaction_diagram4">
<mediaobject>
<imageobject>
<objectinfo>
<title>reaction_diagram4</title>
</objectinfo>
<imagedata fileref="../images/renal_ionic_transport_model/H_ATPase_reaction_diagram.gif" />
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<caption>State diagram of the catalytic unit of the H-ATPase. The catalytic unit (E) has two binding sites for H. Symbols with the asterisk (*) indicate conformations of the catalytic unit in which the binding sites face the cytosol, and symbols without the asterisk represent conformations in which the binding sites face the antechamber. Transition between the unloaded conformations is coupled with ATP synthesis/hydrolysis.</caption>
</informalfigure>
</sect1>
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