/Users/max_neal/Dropbox/Semantic Project/Annotated CellML models/chang_fujita_2001/chang_fujita_2001_H_ATPase.cellml
<documentation xmlns="http://cellml.org/tmp-documentation"> <articleinfo> Mathematical Models of Ionic Transport in the Distal Tubule of the Rat <author> <firstname>Catherine</firstname> <surname>Lloyd</surname> <affiliation> <shortaffil>Auckland Bioengineering Institute, The University of Auckland</shortaffil> </affiliation> </author> </articleinfo> Model Status This CellML model is a 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. <sect1 id="sec_structure"> Model Structure ABSTRACT: The purpose of this study is to develop a numerical model that simulates acid-base transport in rat distal tubule. We have previously reported a model that deals with transport of Na(+), K(+), Cl(-), and water in this nephron segment (Chang H and Fujita T. Am J Physiol Renal Physiol 276: F931-F951, 1999). In this study, we extend our previous model by incorporating buffer systems, new cell types, and new transport mechanisms. Specifically, the model incorporates bicarbonate, ammonium, and phosphate buffer systems; has cell types corresponding to intercalated cells; and includes the Na/H exchanger, H-ATPase, and anion exchanger. Incorporation of buffer systems has required the following modifications of model equations: new model equations are introduced to represent chemical equilibria of buffer partners [e.g., pH = pK(a) + log(10) (NH(3)/NH(4))], and the formulation of mass conservation is extended to take into account interconversion of buffer partners. Furthermore, finite rates of H(2)CO(3)-CO(2) interconversion are taken into account in modeling the bicarbonate buffer system. Owing to this treatment, the model can simulate the development of disequilibrium pH in the distal tubular fluid. For each new transporter, a state diagram has been constructed to simulate its transport kinetics. With appropriate assignment of maximal transport rates for individual transporters, the model predictions are in agreement with free-flow micropuncture experiments in terms of HCO reabsorption rate in the normal state as well as under the high bicarbonate load. Although the model cannot simulate all of the microperfusion experiments, especially those that showed a flow-dependent increase in HCO reabsorption, the model is consistent with those microperfusion experiments that showed HCO reabsorption rates similar to those in the free-flow micropuncture experiments. We conclude that it is possible to develop a numerical model of the rat distal tubule that simulates acid-base transport, as well as basic solute and water transport, on the basis of tubular geometry, physical principles, and transporter kinetics. Such a model would provide a useful means of integrating detailed kinetic properties of transporters and predicting macroscopic transport characteristics of this nephron segment under physiological and pathophysiological settings. The original paper reference is cited below: A numerical model of acid-base transport in rat distal tubule, Hangil Chang and Toshiro Fujita, 2001, American Journal of Physiology , 281, F222-F243. PubMed ID: 11457714 . <informalfigure float="0" id="fig_reaction_diagram3"> <mediaobject> <imageobject> <objectinfo> reaction_diagram3 </objectinfo> <imagedata fileref="chang_2001c.png" /> </imageobject> </mediaobject> 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. </informalfigure> <informalfigure float="0" id="fig_reaction_diagram4"> <mediaobject> <imageobject> <objectinfo> reaction_diagram4 </objectinfo> <imagedata fileref="chang_2001d.png" /> </imageobject> </mediaobject> 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. </informalfigure> </sect1> </documentation>
<rdf:RDF xmlns:cmeta="http://www.cellml.org/metadata/1.0#" xmlns:rdf="http://www.w3.org/1999/02/22-rdf-syntax-ns#" xmlns:vCard="http://www.w3.org/2001/vcard-rdf/3.0#" xmlns:bqs="http://www.cellml.org/bqs/1.0#" xmlns:j.0="http://imc.org/vCard/3.0#" xmlns:dc="http://purl.org/dc/elements/1.1/" xmlns:dcterms="http://purl.org/dc/terms/"> <rdf:Description rdf:about="http://www.cellml.org/cellml/1.0#renal_H_ATPase_model"> <cmeta:species>Rat</cmeta:species> <bqs:reference> <rdf:Description rdf:about="rdf:#ae6916fd-29d2-4763-a0ba-79ceec299157"> <bqs:JournalArticle> <rdf:Description rdf:about="rdf:#cd12d814-dc56-4756-825b-8bc1b2408625"> <bqs:last_page>F243</bqs:last_page> <dcterms:issued> <rdf:Description rdf:about="rdf:#6ca7c35d-64e6-4d14-bc97-937bd12069ce"> <dcterms:W3CDTF>2001-08</dcterms:W3CDTF> </rdf:Description> </dcterms:issued> <bqs:Journal> <rdf:Description rdf:about="rdf:#3a4bd135-2eb3-45c4-93ed-bad58aa3d1d2"> <dc:title>American Journal of Physiology</dc:title> </rdf:Description> </bqs:Journal> <bqs:first_page>F222</bqs:first_page> <bqs:volume>281</bqs:volume> <dc:title>A numerical model of acid-base transport in rat distal tubule</dc:title> <dc:creator> <rdf:Seq rdf:about="rdf:#5983efbf-2cf8-4d36-9de5-10ca91e31540"> <rdf:li> <bqs:Person rdf:about="rdf:#b07d2d63-b508-4b0d-9f19-90f956ba1108"> <vCard:N> <rdf:Description rdf:about="rdf:#08a1413b-bdd3-44d2-a58d-5e63804335c7"> <vCard:Family>Chang</vCard:Family> <vCard:Given>Hangil</vCard:Given> </rdf:Description> </vCard:N> </bqs:Person> </rdf:li> <rdf:li> <bqs:Person rdf:about="rdf:#d07e5835-41b3-4589-a6dc-1f166446c113"> <vCard:N> <rdf:Description rdf:about="rdf:#a4fdda4e-fb2d-486a-b0f9-52e630ad30f4"> <vCard:Family>Fujita</vCard:Family> <vCard:Given>Toshiro</vCard:Given> </rdf:Description> </vCard:N> </bqs:Person> </rdf:li> </rdf:Seq> </dc:creator> </rdf:Description> </bqs:JournalArticle> <bqs:Pubmed_id>11457714</bqs:Pubmed_id> </rdf:Description> </bqs:reference> <bqs:reference> <rdf:Description rdf:about="rdf:#25307320-acfc-4d52-b152-79c3b61ae355"> <dc:subject> <rdf:Description rdf:about="rdf:#8efd9e1e-2923-41fc-b13b-f5703584df68"> <rdf:value> <rdf:Bag rdf:about="rdf:#35acf3e3-18b1-4518-bde2-8cfd8c7ee1ed"> <rdf:li>kidney</rdf:li> <rdf:li>electrophysiology</rdf:li> <rdf:li>distal tubule</rdf:li> <rdf:li>renal</rdf:li> <rdf:li>acid-base transport</rdf:li> <rdf:li>ion transport</rdf:li> </rdf:Bag> </rdf:value> <bqs:subject_type>keyword</bqs:subject_type> </rdf:Description> </dc:subject> </rdf:Description> </bqs:reference> <cmeta:comment> <rdf:Description rdf:about="rdf:#9e6c1010-5605-4a78-9992-5403125ce223"> <rdf:value>This is the 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. These models can be run in PCEnv but they give a flat output. I suspect they need to be embedded within a whole cell model in order to give a reasonable output.</rdf:value> <dc:creator> <rdf:Description rdf:about="rdf:#92dbb897-b5d4-4696-b11c-ad6b55d5332f"> <vCard:FN>Catherine Lloyd</vCard:FN> </rdf:Description> </dc:creator> </rdf:Description> </cmeta:comment> <cmeta:bio_entity>Renal Distal Tubule</cmeta:bio_entity> <dc:title>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.</dc:title> </rdf:Description> <rdf:Description rdf:about="http://www.cellml.org/cellml/1.0"> <cmeta:modification> <rdf:Description rdf:about="rdf:#35902352-7cc0-4181-bf07-f1f73e90956b"> <cmeta:modifier> <rdf:Description rdf:about="rdf:#d88da72b-8a46-453b-adbe-3f53e7be8036"> <vCard:N> <rdf:Description rdf:about="rdf:#7abcf947-9092-4800-9056-bf5da0cbeb2d"> <vCard:Other>May</vCard:Other> <vCard:Family>Lloyd</vCard:Family> <vCard:Given>Catherine</vCard:Given> </rdf:Description> </vCard:N> </rdf:Description> </cmeta:modifier> <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. The model runs in the PCEnv simulator but gives a flat output.</rdf:value> <dcterms:modified> <rdf:Description rdf:about="rdf:#525c17d9-ad8f-425f-9732-3468096c2fcc"> <dcterms:W3CDTF>2007-06-05T09:56:00+12:00</dcterms:W3CDTF> </rdf:Description> </dcterms:modified> </rdf:Description> </cmeta:modification> <dc:creator> <rdf:Description rdf:about="rdf:#bd9ee214-d7c0-4738-9b8f-aa6dbb2fc0e5"> <vCard:N> <rdf:Description rdf:about="rdf:#a5a71012-dc0b-43fb-9da5-73558f9d8700"> <vCard:Other>May</vCard:Other> <vCard:Family>Lloyd</vCard:Family> <vCard:Given>Catherine</vCard:Given> </rdf:Description> </vCard:N> <vCard:EMAIL> <j.0:internet rdf:about="rdf:#6d779a8c-1830-4c79-b105-a26f6a24de90"> <rdf:value>c.lloyd@auckland.ac.nz</rdf:value> </j.0:internet> </vCard:EMAIL> <vCard:ORG> <rdf:Description rdf:about="rdf:#1874a94e-ffba-42b8-b3b9-91ee526a18b7"> <vCard:Orgunit>Auckland Bioengineering Institute</vCard:Orgunit> <vCard:Orgname>The University of Auckland</vCard:Orgname> </rdf:Description> </vCard:ORG> </rdf:Description> </dc:creator> <dcterms:created> <rdf:Description rdf:about="rdf:#df754649-a053-4044-a5b2-6caf16dd5350"> <dcterms:W3CDTF>2007-05-29T00:00:00+00:00</dcterms:W3CDTF> </rdf:Description> </dcterms:created> <cmeta:comment> <rdf:Description rdf:about="rdf:#6178f046-fbaf-4065-9f92-f172a5230666"> <rdf:value></rdf:value> <dc:creator> <rdf:Description rdf:about="rdf:#c29cc0b6-14f4-4866-84c0-f9fd689980db"> <vCard:FN></vCard:FN> </rdf:Description> </dc:creator> </rdf:Description> </cmeta:comment> <dc:publisher>The University of Auckland, Auckland Bioengineering Institute</dc:publisher> <dc:title>H-ATPase</dc:title> </rdf:Description> </rdf:RDF>
Maxwell Neal
renal_H_ATPase_model
Temperature
Chemical concentration
Electrical potential
ATP
ADP
phosphate(3-)
proton
renal alpha-intercalated cell
plasma membrane proton-transporting V-type ATPase, V1 domain
Portion of cytosol
Portion of extracellular matrix
A physical entity that is defined by linking multiple physical entity terms with structural relations.
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An element of a SemSim model that relates to the mathematical or logical representation of physical quantities or qualities.
A physical dependency defined in a specific SemSim model.
A physical entity defined in a specific SemSim model.
A physical process defined in a specific SemSim model.
A physical property defined in a specific SemSim model.
A computational element that stores numerical and/or logical information related to the model.
A data structure whose value is limited to decimals.
A data structure whose value is limited to the whole numbers.
A data structure unique to JSim's Mathematical Modeling Language (MML) used to set one or more model input values at runtime.
A quantitative relation between values of physical properties that occurs over a span of time and that determines the time-course of a physical process.
A physics analytical entity that represents the material, energy, and/or information content of material or immaterial, space-occupying continuants.
A SemSim model element used to represent, in whole or in part, the physical meaning of a computational element.
A physical processural entity that is a flow, or the control of a flow, of energy and/or information amongst physical continuants that are participants in the physical process.
A physical attribute of an instance of a physical entity, an occurrence of a physical process, or a physical dependency that has a quantitative value that is measurable by a physical device or method, or is computable from such values.
A data structure whose value is limited to the real numbers.
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A physical entity that is defined using a term from an external knowledge resource.
A physical process that is defined using a term in an external knowledge resource.
A physical property that is defined using a term in an external knowledge resource.
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A computational or physical element of a SemSim model.
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Antechamber-facing conformation of H-ATPase catalytic component
Antechamber of H-ATPase
The buffer space between the membrane and catalytic components of H-ATPase
Cytosol-facing conformation of H-ATPase catalytic component
Double proton-bound, antechamber-facing conformation of H-ATPase catalytic component
Double proton-bound, cytosol-facing conformation of H-ATPase catalytic component
Cytosolic ADP concentration in type-A intercalated cells of late distal tubule
Cytosolic ATP concentration in type-A intercalated cells of late distal tubule
Concentration of antechamber-facing conformation of H-ATPase catalytic component
Concentration of proton-bound, antechamber-facing conformation of H-ATPase catalytic component
Concentration of cytosol-facing conformation of H-ATPase catalytic component
H+ concentration in the antechamber between the membrane and catalytic components of H-ATPase
Cytosolic phosphate(3-) concentration in type-A intercalated cells of late distal tubule
Forward rate constant for proton binding to antechamber-facing conformation of H-ATPase catalytic component
Backward rate constant for conformational change of H-ATPase catalytic component from antechamber-facing to cytosol-facing
Backward rate constant for proton binding to antechamber-facing conformation of H-ATPase catalytic component
Forward rate constant for conformational change of H-ATPase catalytic component from antechamber-facing to cytosol-facing
Time
Time solution domain for simulation
Concentration of double proton-bound, antechamber-facing conformation of H-ATPase catalytic component
Forward rate constant for proton binding to the proton-bound, antechamber-facing conformation of H-ATPase catalytic component
Backward rate constant for proton binding to the proton-bound, antechamber-facing conformation of H-ATPase catalytic component
Concentration of double proton-bound, cytosol-facing conformation of H-ATPase catalytic component
Forward rate constant for conformational change of double proton-bound H-ATPase catalytic component from antechamber-facing to cytosol-facing
Backward rate constant for conformational change of double proton-bound H-ATPase catalytic component from antechamber-facing to cytosol-facing
Concentration of proton-bound, cytosol-facing conformation of H-ATPase catalytic component
H+ concentration in the cytosolic space
Forward rate constant for proton binding to the proton-bound, cytosol-facing conformation of H-ATPase catalytic component
Backward rate constant for proton binding to the proton-bound, cytosol-facing conformation of H-ATPase catalytic component
<apply> <eq /> <apply> <diff /> <bvar> <ci>time</ci> </bvar> <ci>EH2_</ci> </apply> <apply> <minus /> <apply> <plus /> <apply> <times /> <ci>k7</ci> <ci>H_</ci> <ci>EH_</ci> </apply> <apply> <times /> <ci>k11</ci> <ci>EH2</ci> </apply> </apply> <apply> <plus /> <apply> <times /> <ci>k8</ci> <ci>EH2_</ci> </apply> <apply> <times /> <ci>k12</ci> <ci>EH2_</ci> </apply> </apply> </apply> </apply>
<apply> <eq /> <apply> <diff /> <bvar> <ci>time</ci> </bvar> <ci>EH2</ci> </apply> <apply> <minus /> <apply> <plus /> <apply> <times /> <ci>k3</ci> <ci>Ha</ci> <ci>EH</ci> </apply> <apply> <times /> <ci>k12</ci> <ci>EH2_</ci> </apply> </apply> <apply> <plus /> <apply> <times /> <ci>k4</ci> <ci>EH2</ci> </apply> <apply> <times /> <ci>k11</ci> <ci>EH2</ci> </apply> </apply> </apply> </apply>
Forward rate constant for proton binding to cytosol-facing conformation of H-ATPase catalytic component
Backward rate constant for proton binding to cytosol-facing conformation of H-ATPase catalytic component
<apply> <eq /> <apply> <diff /> <bvar> <ci>time</ci> </bvar> <ci>EH_</ci> </apply> <apply> <minus /> <apply> <plus /> <apply> <times /> <ci>k5</ci> <ci>H_</ci> <ci>E_</ci> </apply> <apply> <times /> <ci>k8</ci> <ci>EH2_</ci> </apply> </apply> <apply> <plus /> <apply> <times /> <ci>k6</ci> <ci>EH_</ci> </apply> <apply> <times /> <ci>k7</ci> <ci>H_</ci> <ci>EH_</ci> </apply> </apply> </apply> </apply>
<apply> <eq /> <apply> <diff /> <bvar> <ci>time</ci> </bvar> <ci>EH</ci> </apply> <apply> <minus /> <apply> <plus /> <apply> <times /> <ci>k1</ci> <ci>Ha</ci> <ci>E</ci> </apply> <apply> <times /> <ci>k4</ci> <ci>EH2</ci> </apply> </apply> <apply> <plus /> <apply> <times /> <ci>k2</ci> <ci>EH</ci> </apply> <apply> <times /> <ci>k3</ci> <ci>Ha</ci> <ci>EH</ci> </apply> </apply> </apply> </apply>
<apply> <eq /> <apply> <diff /> <bvar> <ci>time</ci> </bvar> <ci>E_</ci> </apply> <apply> <minus /> <apply> <plus /> <apply> <times /> <ci>k9</ci> <ci>ATP_</ci> <ci>E</ci> </apply> <apply> <times /> <ci>k6</ci> <ci>EH_</ci> </apply> </apply> <apply> <plus /> <apply> <times /> <ci>k5</ci> <ci>H_</ci> <ci>E_</ci> </apply> <apply> <times /> <ci>k10</ci> <ci>ADP_</ci> <ci>Pi_</ci> <ci>E_</ci> </apply> </apply> </apply> </apply>
<apply> <eq /> <apply> <diff /> <bvar> <ci>time</ci> </bvar> <ci>E</ci> </apply> <apply> <minus /> <apply> <plus /> <apply> <times /> <ci>k10</ci> <ci>ADP_</ci> <ci>Pi_</ci> <ci>E_</ci> </apply> <apply> <times /> <ci>k2</ci> <ci>EH</ci> </apply> </apply> <apply> <plus /> <apply> <times /> <ci>k1</ci> <ci>Ha</ci> <ci>E</ci> </apply> <apply> <times /> <ci>k9</ci> <ci>ATP_</ci> <ci>E</ci> </apply> </apply> </apply> </apply>
Late distal tubule
The authors distinguish between "early" and "late" segments of the distal tubule. The early segment is the distal convoluted tubule, the late segment is composed of the connecting tubule and the initial collecting tubule.
Proton-bound, antechamber-facing conformation of H-ATPase catalytic component
Proton-bound, cytosol-facing conformation of H-ATPase catalytic component
Faraday constant
Extracellular H+ concentration
Gas constant
Ambient temperature
Extracellular electrical potential
Intraceullar electrical potential
<apply> <eq /> <ci>Ha</ci> <apply> <times /> <ci>H</ci> <apply> <exp /> <apply> <divide /> <apply> <times /> <ci>F</ci> <apply> <plus /> <ci>psi</ci> <ci>psi_</ci> </apply> </apply> <apply> <times /> <ci>R</ci> <ci>T</ci> </apply> </apply> </apply> </apply> </apply>