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BIOMD0000000569.xml
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3652 lines (3645 loc) · 156 KB
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<?xml version='1.0' encoding='UTF-8' standalone='no'?>
<!-- This model was downloaded from BioModels Database -->
<!-- Mon Jun 26 21:51:07 BST 2017 -->
<!-- http://www.ebi.ac.uk/biomodels/ -->
<sbml xmlns="http://www.sbml.org/sbml/level2/version4" level="2" metaid="efa57873-0876-42e0-8d2c-7689cfb1c933" version="4">
<model id="MODEL1407160000" metaid="COPASI0" name="Dutta-Roy2015 - Opening of the multiple AMPA receptor conductance states">
<notes>
<body xmlns="http://www.w3.org/1999/xhtml">
<div class="dc:title">Dutta-Roy2015 - Opening of the multiple AMPA
receptor conductance states</div>
<div class="dc:bibliographicCitation">
<p>This model is described in the article:</p>
<div class="bibo:title">
<a href="http://identifiers.org/pubmed/25629405" title="Access to this publication">Ligand-dependent opening of
the multiple AMPA receptor conductance States: a concerted
model.</a>
</div>
<div class="bibo:authorList">Dutta-Roy R, Rosenmund C, Edelstein
SJ, Le Novère N.</div>
<div class="bibo:Journal">PLoS ONE 2015; 10(1): e0116616</div>
<p>Abstract:</p>
<div class="bibo:abstract">
<p>Modulation of the properties of AMPA receptors at the
post-synaptic membrane is one of the main suggested mechanisms
underlying fast synaptic transmission in the central nervous
system of vertebrates. Electrophysiological recordings of
single channels stimulated with agonists showed that both
recombinant and native AMPA receptors visit multiple
conductance states in an agonist concentration dependent
manner. We propose an allosteric model of the multiple
conductance states based on concerted conformational
transitions of the four subunits, as an iris diaphragm. Our
model predicts that the thermodynamic behaviour of the
conductance states upon full and partial agonist stimulations
can be described with increased affinity of receptors as they
progress to higher conductance states. The model also predicts
the existence of AMPA receptors in non-liganded conductive
substates. However, the probability of spontaneous openings
decreases with increasing conductances. Finally, we predict
that the large conductance states are stabilized within the
rise phase of a whole-cell EPSC in glutamatergic hippocampal
neurons. Our model provides a mechanistic link between ligand
concentration and conductance states that can explain
thermodynamic and kinetic features of AMPA receptor gating.</p>
</div>
</div>
<div class="dc:publisher">
<p>This model is hosted on
<a href="http://www.ebi.ac.uk/biomodels/">BioModels Database</a>
and identified by:
<a href="http://identifiers.org/biomodels.db/BIOMD0000000569">BIOMD0000000569</a>.</p>
<p>To cite BioModels Database, please use:
<a href="http://identifiers.org/pubmed/20587024" title="Latest BioModels Database publication">BioModels Database:
An enhanced, curated and annotated resource for published
quantitative kinetic models</a>.</p>
</div>
<div class="dc:license">
<p>To the extent possible under law, all copyright and related or
neighbouring rights to this encoded model have been dedicated to
the public domain worldwide. Please refer to
<a href="http://creativecommons.org/publicdomain/zero/1.0/" title="Access to: CC0 1.0 Universal (CC0 1.0), Public Domain Dedication">CC0
Public Domain Dedication</a> for more information.</p>
</div>
</body>
</notes>
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<rdf:Description rdf:about="#COPASI0">
<dcterms:created>
<rdf:Description>
<dcterms:W3CDTF>2014-07-02T11:14:45Z</dcterms:W3CDTF>
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<vCard:N rdf:parseType="Resource">
<vCard:Family>Le Novère</vCard:Family>
<vCard:Given>Nicolas</vCard:Given>
</vCard:N>
<vCard:EMAIL>n.lenovere@gmail.com</vCard:EMAIL>
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<vCard:Orgname>Babraham Institute</vCard:Orgname>
</vCard:ORG>
</rdf:li>
<rdf:li rdf:parseType="Resource">
<vCard:N rdf:parseType="Resource">
<vCard:Family>Lloret i Villas</vCard:Family>
<vCard:Given>Audald</vCard:Given>
</vCard:N>
<vCard:EMAIL>lloret@ebi.ac.uk</vCard:EMAIL>
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<dcterms:W3CDTF>2016-04-08T17:53:05Z</dcterms:W3CDTF>
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<functionDefinition id="Ligand_Binding_1" metaid="COPASI102" name="Ligand Binding 1">
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<ci> L </ci>
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<times/>
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<ci> k </ci>
<ci> R </ci>
<ci> L </ci>
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<ci> k </ci>
<ci> R </ci>
<ci> L </ci>
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</rdf:Description>
</dcterms:created>
</rdf:Description>
</rdf:RDF>
</COPASI>
</annotation>
<math xmlns="http://www.w3.org/1998/Math/MathML">
<lambda>
<bvar>
<ci> k </ci>
</bvar>
<bvar>
<ci> R </ci>
</bvar>
<apply>
<times/>
<cn> 4 </cn>
<ci> k </ci>
<ci> R </ci>
</apply>
</lambda>
</math>
</functionDefinition>
</listOfFunctionDefinitions>
<listOfCompartments>
<compartment constant="true" id="synapse" metaid="COPASI1" name="synapse" size="1E-16" spatialDimensions="3">
<notes>
<body xmlns="http://www.w3.org/1999/xhtml">
<pre>The volume must be divided by 50 (resulting in 2e-18 litre) to simulate a single receptor while keeping the same concentration.</pre>
</body>
</notes>
<annotation>
<COPASI xmlns="http://www.copasi.org/static/sbml">
<rdf:RDF xmlns:dcterms="http://purl.org/dc/terms/" xmlns:rdf="http://www.w3.org/1999/02/22-rdf-syntax-ns#">
<rdf:Description rdf:about="#COPASI1">
<dcterms:created>
<rdf:Description>
<dcterms:W3CDTF>2014-07-02T14:37:18Z</dcterms:W3CDTF>
</rdf:Description>
</dcterms:created>
</rdf:Description>
</rdf:RDF>
</COPASI>
<rdf:RDF xmlns:rdf="http://www.w3.org/1999/02/22-rdf-syntax-ns#" xmlns:bqbiol="http://biomodels.net/biology-qualifiers/">
<rdf:Description rdf:about="#COPASI1">
<bqbiol:is>
<rdf:Bag>
<rdf:li rdf:resource="http://identifiers.org/fma/FMA:55675"/>
</rdf:Bag>
</bqbiol:is>
</rdf:Description>
</rdf:RDF>
</annotation>
</compartment>
</listOfCompartments>
<listOfSpecies>
<species boundaryCondition="false" compartment="synapse" constant="false" hasOnlySubstanceUnits="false" id="B0" initialConcentration="8.30269391581363E-7" metaid="COPASI2" name="B0">
<notes>
<body xmlns="http://www.w3.org/1999/xhtml">
<pre>The amount must be divided by 50 to simulate a single receptor (scale down the volume too).</pre>
</body>
</notes>
<annotation>
<COPASI xmlns="http://www.copasi.org/static/sbml">
<rdf:RDF xmlns:CopasiMT="http://www.copasi.org/RDF/MiriamTerms#" xmlns:dcterms="http://purl.org/dc/terms/" xmlns:rdf="http://www.w3.org/1999/02/22-rdf-syntax-ns#">
<rdf:Description rdf:about="#COPASI2">
<dcterms:created>
<rdf:Description>
<dcterms:W3CDTF>2014-07-02T14:37:50Z</dcterms:W3CDTF>
</rdf:Description>
</dcterms:created>
<CopasiMT:hasPart rdf:resource="http://identifiers.org/uniprot/P42263"/>
<CopasiMT:hasPart rdf:resource="http://identifiers.org/uniprot/Q13002"/>
</rdf:Description>
</rdf:RDF>
</COPASI>
<rdf:RDF xmlns:rdf="http://www.w3.org/1999/02/22-rdf-syntax-ns#" xmlns:bqbiol="http://biomodels.net/biology-qualifiers/">
<rdf:Description rdf:about="#COPASI2">
<bqbiol:hasPart>
<rdf:Bag>
<rdf:li rdf:resource="http://identifiers.org/uniprot/Q13002"/>
</rdf:Bag>
</bqbiol:hasPart>
<bqbiol:hasPart>
<rdf:Bag>
<rdf:li rdf:resource="http://identifiers.org/uniprot/P42263"/>
</rdf:Bag>
</bqbiol:hasPart>
</rdf:Description>
</rdf:RDF>
</annotation>
</species>
<species boundaryCondition="false" compartment="synapse" constant="false" hasOnlySubstanceUnits="false" id="S0" initialConcentration="0" metaid="COPASI3" name="S0">
<annotation>
<COPASI xmlns="http://www.copasi.org/static/sbml">
<rdf:RDF xmlns:dcterms="http://purl.org/dc/terms/" xmlns:rdf="http://www.w3.org/1999/02/22-rdf-syntax-ns#">
<rdf:Description rdf:about="#COPASI3">
<dcterms:created>
<rdf:Description>
<dcterms:W3CDTF>2014-07-02T14:50:58Z</dcterms:W3CDTF>
</rdf:Description>
</dcterms:created>
</rdf:Description>
</rdf:RDF>
</COPASI>
</annotation>
</species>
<species boundaryCondition="false" compartment="synapse" constant="false" hasOnlySubstanceUnits="false" id="B1" initialConcentration="0" metaid="_4cae6923-2a50-46dd-9c7d-436a885bdf9a" name="B1"/>
<species boundaryCondition="false" compartment="synapse" constant="false" hasOnlySubstanceUnits="false" id="S1" initialConcentration="0" metaid="_6abde661-e1f5-4d89-b1af-5a57f1b5ee69" name="S1"/>
<species boundaryCondition="false" compartment="synapse" constant="false" hasOnlySubstanceUnits="false" id="B2" initialConcentration="0" metaid="_600c4965-5665-4041-9ffe-79303bcca5e0" name="B2"/>
<species boundaryCondition="false" compartment="synapse" constant="false" hasOnlySubstanceUnits="false" id="S2" initialConcentration="0" metaid="_38353308-52ca-4b22-bdac-0ef2e4a4415f" name="S2"/>
<species boundaryCondition="false" compartment="synapse" constant="false" hasOnlySubstanceUnits="false" id="B3" initialConcentration="0" metaid="_46962d57-eaaf-4f52-bac9-2d31d38c6880" name="B3"/>
<species boundaryCondition="false" compartment="synapse" constant="false" hasOnlySubstanceUnits="false" id="S3" initialConcentration="0" metaid="dc9b7c79-cbd5-4838-8042-a5535b9af5a7" name="S3"/>
<species boundaryCondition="false" compartment="synapse" constant="false" hasOnlySubstanceUnits="false" id="B4" initialConcentration="0" metaid="f16cad17-a827-4e7f-a7ec-844bda49e7ab" name="B4"/>
<species boundaryCondition="false" compartment="synapse" constant="false" hasOnlySubstanceUnits="false" id="S4" initialConcentration="0" metaid="_1a57da8f-93ed-4ef1-886c-1222614eddd3" name="S4"/>
<species boundaryCondition="false" compartment="synapse" constant="false" hasOnlySubstanceUnits="false" id="M0" initialConcentration="0" metaid="d0b94bf1-af23-4ec3-95bc-ec6609c6be2a" name="M0"/>
<species boundaryCondition="false" compartment="synapse" constant="false" hasOnlySubstanceUnits="false" id="M1" initialConcentration="0" metaid="_576826f5-c6c2-40fa-9d8b-f23cdbb5375e" name="M1"/>
<species boundaryCondition="false" compartment="synapse" constant="false" hasOnlySubstanceUnits="false" id="M2" initialConcentration="0" metaid="ca324889-1a61-47d9-ab92-00cb6b594813" name="M2"/>
<species boundaryCondition="false" compartment="synapse" constant="false" hasOnlySubstanceUnits="false" id="M3" initialConcentration="0" metaid="_570d4af5-4f4d-47cf-a2c6-83222559321d" name="M3"/>
<species boundaryCondition="false" compartment="synapse" constant="false" hasOnlySubstanceUnits="false" id="M4" initialConcentration="0" metaid="a83caf43-4b99-4838-bf22-7e76d30b029b" name="M4"/>
<species boundaryCondition="false" compartment="synapse" constant="false" hasOnlySubstanceUnits="false" id="L0" initialConcentration="0" metaid="a938ae9a-1512-48f4-93a6-b011b877d406" name="L0"/>
<species boundaryCondition="false" compartment="synapse" constant="false" hasOnlySubstanceUnits="false" id="L1" initialConcentration="0" metaid="d959d985-2fa8-4365-a527-df842cabb678" name="L1"/>
<species boundaryCondition="false" compartment="synapse" constant="false" hasOnlySubstanceUnits="false" id="L2" initialConcentration="0" metaid="_6ccd119f-6d1b-4ba6-9c99-2c6c997cc7a4" name="L2"/>
<species boundaryCondition="false" compartment="synapse" constant="false" hasOnlySubstanceUnits="false" id="L3" initialConcentration="0" metaid="c50f57a4-76bc-4893-a254-8fc886b13f05" name="L3"/>
<species boundaryCondition="false" compartment="synapse" constant="false" hasOnlySubstanceUnits="false" id="L4" initialConcentration="0" metaid="_4aa64b9c-c631-4fc1-a4b3-5a92f34e7c10" name="L4"/>
<species boundaryCondition="false" compartment="synapse" constant="false" hasOnlySubstanceUnits="false" id="glu" initialConcentration="0.000830269391581363" metaid="COPASI4" name="glu">
<annotation>
<COPASI xmlns="http://www.copasi.org/static/sbml">
<rdf:RDF xmlns:dcterms="http://purl.org/dc/terms/" xmlns:rdf="http://www.w3.org/1999/02/22-rdf-syntax-ns#">
<rdf:Description rdf:about="#COPASI4">
<dcterms:created>
<rdf:Description>
<dcterms:W3CDTF>2014-07-02T14:40:12Z</dcterms:W3CDTF>
</rdf:Description>
</dcterms:created>
</rdf:Description>
</rdf:RDF>
</COPASI>
<rdf:RDF xmlns:rdf="http://www.w3.org/1999/02/22-rdf-syntax-ns#" xmlns:bqbiol="http://biomodels.net/biology-qualifiers/">
<rdf:Description rdf:about="#COPASI4">
<bqbiol:is>
<rdf:Bag>
<rdf:li rdf:resource="http://identifiers.org/chebi/CHEBI:18237"/>
</rdf:Bag>
</bqbiol:is>
</rdf:Description>
</rdf:RDF>
</annotation>
</species>
</listOfSpecies>
<listOfParameters>
<parameter constant="true" id="Bkon" metaid="COPASI5" name="Bkon" value="5000000">
<annotation>
<COPASI xmlns="http://www.copasi.org/static/sbml">
<rdf:RDF xmlns:dcterms="http://purl.org/dc/terms/" xmlns:rdf="http://www.w3.org/1999/02/22-rdf-syntax-ns#">
<rdf:Description rdf:about="#COPASI5">
<dcterms:created>
<rdf:Description>
<dcterms:W3CDTF>2014-07-02T11:22:06Z</dcterms:W3CDTF>
</rdf:Description>
</dcterms:created>
</rdf:Description>
</rdf:RDF>
</COPASI>
</annotation>
</parameter>
<parameter constant="true" id="Bkoff" metaid="COPASI6" name="Bkoff" value="4495">
<annotation>
<COPASI xmlns="http://www.copasi.org/static/sbml">
<rdf:RDF xmlns:dcterms="http://purl.org/dc/terms/" xmlns:rdf="http://www.w3.org/1999/02/22-rdf-syntax-ns#">
<rdf:Description rdf:about="#COPASI6">
<dcterms:created>
<rdf:Description>
<dcterms:W3CDTF>2014-07-02T12:59:44Z</dcterms:W3CDTF>
</rdf:Description>
</dcterms:created>
</rdf:Description>
</rdf:RDF>
</COPASI>
</annotation>
</parameter>
<parameter constant="true" id="Skon" metaid="COPASI7" name="Skon" value="5000000">
<annotation>
<COPASI xmlns="http://www.copasi.org/static/sbml">
<rdf:RDF xmlns:dcterms="http://purl.org/dc/terms/" xmlns:rdf="http://www.w3.org/1999/02/22-rdf-syntax-ns#">
<rdf:Description rdf:about="#COPASI7">
<dcterms:created>
<rdf:Description>
<dcterms:W3CDTF>2014-07-02T11:22:23Z</dcterms:W3CDTF>
</rdf:Description>
</dcterms:created>
</rdf:Description>
</rdf:RDF>
</COPASI>
</annotation>
</parameter>
<parameter constant="true" id="Skoff" metaid="f703c769-45a4-4b7d-8b0d-8976fb3784f9" name="Skoff" value="270.4"/>
<parameter constant="true" id="Mkon" metaid="_0ac6c9e9-21e0-4d9c-9c1c-f61cadb0cb40" name="Mkon" value="5000000"/>
<parameter constant="true" id="Mkoff" metaid="_6571e99a-303d-4b5f-8db1-6045d0b61843" name="Mkoff" value="16.65"/>
<parameter constant="true" id="Lkon" metaid="_01883aae-ca8b-4811-bde1-4e363c8c0940" name="Lkon" value="5000000"/>
<parameter constant="true" id="Lkoff" metaid="_72493ccc-2478-4ee3-b166-456b1a161ad0" name="Lkoff" value="1.149"/>
<parameter constant="true" id="BSk0" metaid="COPASI8" name="BSk0" value="1083.603">
<annotation>
<COPASI xmlns="http://www.copasi.org/static/sbml">
<rdf:RDF xmlns:dcterms="http://purl.org/dc/terms/" xmlns:rdf="http://www.w3.org/1999/02/22-rdf-syntax-ns#">
<rdf:Description rdf:about="#COPASI8">
<dcterms:created>
<rdf:Description>
<dcterms:W3CDTF>2014-07-02T12:56:46Z</dcterms:W3CDTF>
</rdf:Description>
</dcterms:created>
</rdf:Description>
</rdf:RDF>
</COPASI>
</annotation>
</parameter>
<parameter constant="true" id="SBk0" metaid="COPASI9" name="SBk0" value="2.38094578918663E5">
<annotation>
<COPASI xmlns="http://www.copasi.org/static/sbml">
<rdf:RDF xmlns:dcterms="http://purl.org/dc/terms/" xmlns:rdf="http://www.w3.org/1999/02/22-rdf-syntax-ns#">
<rdf:Description rdf:about="#COPASI9">
<dcterms:created>
<rdf:Description>
<dcterms:W3CDTF>2014-07-02T12:58:19Z</dcterms:W3CDTF>
</rdf:Description>
</dcterms:created>
</rdf:Description>
</rdf:RDF>
</COPASI>
</annotation>
</parameter>
<parameter constant="true" id="BSk1" metaid="COPASI10" name="BSk1" value="4420.10883237053">
<annotation>
<COPASI xmlns="http://www.copasi.org/static/sbml">
<rdf:RDF xmlns:dcterms="http://purl.org/dc/terms/" xmlns:rdf="http://www.w3.org/1999/02/22-rdf-syntax-ns#">
<rdf:Description rdf:about="#COPASI10">
<dcterms:created>
<rdf:Description>
<dcterms:W3CDTF>2014-07-02T12:55:56Z</dcterms:W3CDTF>
</rdf:Description>
</dcterms:created>
</rdf:Description>
</rdf:RDF>
</COPASI>
</annotation>
</parameter>
<parameter constant="true" id="SBk1" metaid="COPASI11" name="SBk1" value="5.83696035062632E4">
<annotation>
<COPASI xmlns="http://www.copasi.org/static/sbml">
<rdf:RDF xmlns:dcterms="http://purl.org/dc/terms/" xmlns:rdf="http://www.w3.org/1999/02/22-rdf-syntax-ns#">
<rdf:Description rdf:about="#COPASI11">
<dcterms:created>
<rdf:Description>
<dcterms:W3CDTF>2014-07-02T12:57:37Z</dcterms:W3CDTF>
</rdf:Description>
</dcterms:created>
</rdf:Description>
</rdf:RDF>
</COPASI>
</annotation>
</parameter>
<parameter constant="true" id="BSk2" metaid="COPASI12" name="BSk2" value="18030">
<annotation>
<COPASI xmlns="http://www.copasi.org/static/sbml">
<rdf:RDF xmlns:dcterms="http://purl.org/dc/terms/" xmlns:rdf="http://www.w3.org/1999/02/22-rdf-syntax-ns#">
<rdf:Description rdf:about="#COPASI12">
<dcterms:created>
<rdf:Description>
<dcterms:W3CDTF>2014-07-02T12:46:38Z</dcterms:W3CDTF>
</rdf:Description>
</dcterms:created>
</rdf:Description>
</rdf:RDF>
</COPASI>
</annotation>
</parameter>
<parameter constant="true" id="SBk2" metaid="COPASI13" name="SBk2" value="1.43094841930116E4">
<annotation>
<COPASI xmlns="http://www.copasi.org/static/sbml">
<rdf:RDF xmlns:dcterms="http://purl.org/dc/terms/" xmlns:rdf="http://www.w3.org/1999/02/22-rdf-syntax-ns#">
<rdf:Description rdf:about="#COPASI13">
<dcterms:created>
<rdf:Description>
<dcterms:W3CDTF>2014-07-02T12:47:22Z</dcterms:W3CDTF>
</rdf:Description>
</dcterms:created>
</rdf:Description>
</rdf:RDF>
</COPASI>
</annotation>
</parameter>
<parameter constant="true" id="BSk3" metaid="COPASI14" name="BSk3" value="7.35459040327876E4">
<annotation>
<COPASI xmlns="http://www.copasi.org/static/sbml">
<rdf:RDF xmlns:dcterms="http://purl.org/dc/terms/" xmlns:rdf="http://www.w3.org/1999/02/22-rdf-syntax-ns#">
<rdf:Description rdf:about="#COPASI14">
<dcterms:created>
<rdf:Description>
<dcterms:W3CDTF>2014-07-02T12:41:57Z</dcterms:W3CDTF>
</rdf:Description>
</dcterms:created>
</rdf:Description>
</rdf:RDF>
</COPASI>
</annotation>
</parameter>
<parameter constant="true" id="SBk3" metaid="COPASI15" name="SBk3" value="3508.01317072642">
<annotation>
<COPASI xmlns="http://www.copasi.org/static/sbml">
<rdf:RDF xmlns:dcterms="http://purl.org/dc/terms/" xmlns:rdf="http://www.w3.org/1999/02/22-rdf-syntax-ns#">
<rdf:Description rdf:about="#COPASI15">
<dcterms:created>
<rdf:Description>
<dcterms:W3CDTF>2014-07-02T12:43:49Z</dcterms:W3CDTF>
</rdf:Description>
</dcterms:created>
</rdf:Description>
</rdf:RDF>
</COPASI>
</annotation>
</parameter>
<parameter constant="true" id="BSk4" metaid="COPASI16" name="BSk4" value="300000">
<annotation>
<COPASI xmlns="http://www.copasi.org/static/sbml">
<rdf:RDF xmlns:dcterms="http://purl.org/dc/terms/" xmlns:rdf="http://www.w3.org/1999/02/22-rdf-syntax-ns#">
<rdf:Description rdf:about="#COPASI16">
<dcterms:created>
<rdf:Description>
<dcterms:W3CDTF>2014-07-02T12:45:02Z</dcterms:W3CDTF>
</rdf:Description>
</dcterms:created>
</rdf:Description>
</rdf:RDF>
</COPASI>
</annotation>
</parameter>
<parameter constant="true" id="SBk4" metaid="COPASI17" name="SBk4" value="860">
<annotation>
<COPASI xmlns="http://www.copasi.org/static/sbml">
<rdf:RDF xmlns:dcterms="http://purl.org/dc/terms/" xmlns:rdf="http://www.w3.org/1999/02/22-rdf-syntax-ns#">
<rdf:Description rdf:about="#COPASI17">
<dcterms:created>
<rdf:Description>
<dcterms:W3CDTF>2014-07-02T12:57:29Z</dcterms:W3CDTF>
</rdf:Description>
</dcterms:created>
</rdf:Description>
</rdf:RDF>
</COPASI>
</annotation>
</parameter>
<parameter constant="true" id="SMk0" metaid="COPASI18" name="SMk0" value="75.8912">
<annotation>
<COPASI xmlns="http://www.copasi.org/static/sbml">
<rdf:RDF xmlns:dcterms="http://purl.org/dc/terms/" xmlns:rdf="http://www.w3.org/1999/02/22-rdf-syntax-ns#">
<rdf:Description rdf:about="#COPASI18">
<dcterms:created>
<rdf:Description>
<dcterms:W3CDTF>2014-07-02T13:09:36Z</dcterms:W3CDTF>
</rdf:Description>
</dcterms:created>
</rdf:Description>
</rdf:RDF>
</COPASI>
</annotation>
</parameter>
<parameter constant="true" id="MSk0" metaid="COPASI19" name="MSk0" value="3.82125990892225E4">
<annotation>
<COPASI xmlns="http://www.copasi.org/static/sbml">
<rdf:RDF xmlns:dcterms="http://purl.org/dc/terms/" xmlns:rdf="http://www.w3.org/1999/02/22-rdf-syntax-ns#">
<rdf:Description rdf:about="#COPASI19">
<dcterms:created>
<rdf:Description>
<dcterms:W3CDTF>2014-07-02T11:30:53Z</dcterms:W3CDTF>
</rdf:Description>
</dcterms:created>
</rdf:Description>
</rdf:RDF>
</COPASI>
</annotation>
</parameter>
<parameter constant="true" id="SMk1" metaid="COPASI20" name="SMk1" value="305.774358637215">
<annotation>
<COPASI xmlns="http://www.copasi.org/static/sbml">
<rdf:RDF xmlns:dcterms="http://purl.org/dc/terms/" xmlns:rdf="http://www.w3.org/1999/02/22-rdf-syntax-ns#">
<rdf:Description rdf:about="#COPASI20">
<dcterms:created>
<rdf:Description>
<dcterms:W3CDTF>2014-07-02T13:08:46Z</dcterms:W3CDTF>
</rdf:Description>
</dcterms:created>
</rdf:Description>
</rdf:RDF>
</COPASI>
</annotation>
</parameter>
<parameter constant="true" id="MSk1" metaid="COPASI21" name="MSk1" value="9484.11767724676">
<annotation>
<COPASI xmlns="http://www.copasi.org/static/sbml">
<rdf:RDF xmlns:dcterms="http://purl.org/dc/terms/" xmlns:rdf="http://www.w3.org/1999/02/22-rdf-syntax-ns#">
<rdf:Description rdf:about="#COPASI21">
<dcterms:created>
<rdf:Description>
<dcterms:W3CDTF>2014-07-02T13:24:52Z</dcterms:W3CDTF>
</rdf:Description>
</dcterms:created>
</rdf:Description>
</rdf:RDF>
</COPASI>
</annotation>
</parameter>
<parameter constant="true" id="SMk2" metaid="COPASI22" name="SMk2" value="1232">
<annotation>
<COPASI xmlns="http://www.copasi.org/static/sbml">
<rdf:RDF xmlns:dcterms="http://purl.org/dc/terms/" xmlns:rdf="http://www.w3.org/1999/02/22-rdf-syntax-ns#">
<rdf:Description rdf:about="#COPASI22">
<dcterms:created>
<rdf:Description>
<dcterms:W3CDTF>2014-07-02T13:07:08Z</dcterms:W3CDTF>
</rdf:Description>
</dcterms:created>
</rdf:Description>
</rdf:RDF>
</COPASI>
</annotation>
</parameter>
<parameter constant="true" id="MSk2" metaid="COPASI23" name="MSk2" value="2353.8961038961">
<annotation>
<COPASI xmlns="http://www.copasi.org/static/sbml">
<rdf:RDF xmlns:dcterms="http://purl.org/dc/terms/" xmlns:rdf="http://www.w3.org/1999/02/22-rdf-syntax-ns#">
<rdf:Description rdf:about="#COPASI23">
<dcterms:created>
<rdf:Description>
<dcterms:W3CDTF>2014-07-02T13:14:40Z</dcterms:W3CDTF>
</rdf:Description>
</dcterms:created>
</rdf:Description>
</rdf:RDF>
</COPASI>
</annotation>
</parameter>
<parameter constant="true" id="SMk3" metaid="COPASI24" name="SMk3" value="4963.86945839634">
<annotation>
<COPASI xmlns="http://www.copasi.org/static/sbml">
<rdf:RDF xmlns:dcterms="http://purl.org/dc/terms/" xmlns:rdf="http://www.w3.org/1999/02/22-rdf-syntax-ns#">
<rdf:Description rdf:about="#COPASI24">
<dcterms:created>
<rdf:Description>
<dcterms:W3CDTF>2014-07-02T13:00:03Z</dcterms:W3CDTF>
</rdf:Description>
</dcterms:created>
</rdf:Description>
</rdf:RDF>
</COPASI>
</annotation>
</parameter>
<parameter constant="true" id="MSk3" metaid="COPASI25" name="MSk3" value="584.221648918401">
<annotation>
<COPASI xmlns="http://www.copasi.org/static/sbml">
<rdf:RDF xmlns:dcterms="http://purl.org/dc/terms/" xmlns:rdf="http://www.w3.org/1999/02/22-rdf-syntax-ns#">
<rdf:Description rdf:about="#COPASI25">
<dcterms:created>
<rdf:Description>
<dcterms:W3CDTF>2014-07-02T13:10:34Z</dcterms:W3CDTF>
</rdf:Description>
</dcterms:created>
</rdf:Description>
</rdf:RDF>
</COPASI>
</annotation>
</parameter>
<parameter constant="true" id="SMk4" metaid="COPASI26" name="SMk4" value="20000">
<annotation>
<COPASI xmlns="http://www.copasi.org/static/sbml">
<rdf:RDF xmlns:dcterms="http://purl.org/dc/terms/" xmlns:rdf="http://www.w3.org/1999/02/22-rdf-syntax-ns#">
<rdf:Description rdf:about="#COPASI26">
<dcterms:created>
<rdf:Description>
<dcterms:W3CDTF>2014-07-02T13:00:02Z</dcterms:W3CDTF>
</rdf:Description>
</dcterms:created>
</rdf:Description>
</rdf:RDF>
</COPASI>
</annotation>
</parameter>
<parameter constant="true" id="MSk4" metaid="COPASI27" name="MSk4" value="145">
<annotation>
<COPASI xmlns="http://www.copasi.org/static/sbml">
<rdf:RDF xmlns:dcterms="http://purl.org/dc/terms/" xmlns:rdf="http://www.w3.org/1999/02/22-rdf-syntax-ns#">
<rdf:Description rdf:about="#COPASI27">
<dcterms:created>
<rdf:Description>
<dcterms:W3CDTF>2014-07-02T13:10:30Z</dcterms:W3CDTF>
</rdf:Description>
</dcterms:created>
</rdf:Description>
</rdf:RDF>
</COPASI>
</annotation>
</parameter>
<parameter constant="true" id="MLk0" metaid="COPASI28" name="MLk0" value="238.05">
<annotation>
<COPASI xmlns="http://www.copasi.org/static/sbml">
<rdf:RDF xmlns:dcterms="http://purl.org/dc/terms/" xmlns:rdf="http://www.w3.org/1999/02/22-rdf-syntax-ns#">
<rdf:Description rdf:about="#COPASI28">
<dcterms:created>
<rdf:Description>
<dcterms:W3CDTF>2014-07-02T13:30:44Z</dcterms:W3CDTF>
</rdf:Description>
</dcterms:created>
</rdf:Description>
</rdf:RDF>
</COPASI>
</annotation>
</parameter>
<parameter constant="true" id="LMk0" metaid="COPASI29" name="LMk0" value="1.45137576139466E5">
<annotation>
<COPASI xmlns="http://www.copasi.org/static/sbml">
<rdf:RDF xmlns:dcterms="http://purl.org/dc/terms/" xmlns:rdf="http://www.w3.org/1999/02/22-rdf-syntax-ns#">
<rdf:Description rdf:about="#COPASI29">
<dcterms:created>
<rdf:Description>
<dcterms:W3CDTF>2014-07-02T13:33:40Z</dcterms:W3CDTF>
</rdf:Description>
</dcterms:created>
</rdf:Description>
</rdf:RDF>
</COPASI>
</annotation>
</parameter>
<parameter constant="true" id="MLk1" metaid="COPASI30" name="MLk1" value="906.240862022895">
<annotation>
<COPASI xmlns="http://www.copasi.org/static/sbml">
<rdf:RDF xmlns:dcterms="http://purl.org/dc/terms/" xmlns:rdf="http://www.w3.org/1999/02/22-rdf-syntax-ns#">
<rdf:Description rdf:about="#COPASI30">
<dcterms:created>
<rdf:Description>
<dcterms:W3CDTF>2014-07-02T13:29:59Z</dcterms:W3CDTF>
</rdf:Description>
</dcterms:created>
</rdf:Description>
</rdf:RDF>
</COPASI>
</annotation>
</parameter>
<parameter constant="true" id="LMk1" metaid="COPASI31" name="LMk1" value="3.81245223514619E4">
<annotation>
<COPASI xmlns="http://www.copasi.org/static/sbml">
<rdf:RDF xmlns:dcterms="http://purl.org/dc/terms/" xmlns:rdf="http://www.w3.org/1999/02/22-rdf-syntax-ns#">
<rdf:Description rdf:about="#COPASI31">
<dcterms:created>
<rdf:Description>
<dcterms:W3CDTF>2014-07-02T13:33:10Z</dcterms:W3CDTF>
</rdf:Description>
</dcterms:created>
</rdf:Description>
</rdf:RDF>
</COPASI>
</annotation>
</parameter>
<parameter constant="true" id="MLk2" metaid="COPASI32" name="MLk2" value="3450">
<annotation>
<COPASI xmlns="http://www.copasi.org/static/sbml">
<rdf:RDF xmlns:dcterms="http://purl.org/dc/terms/" xmlns:rdf="http://www.w3.org/1999/02/22-rdf-syntax-ns#">
<rdf:Description rdf:about="#COPASI32">
<dcterms:created>
<rdf:Description>
<dcterms:W3CDTF>2014-07-02T13:29:09Z</dcterms:W3CDTF>
</rdf:Description>
</dcterms:created>
</rdf:Description>
</rdf:RDF>
</COPASI>
</annotation>
</parameter>
<parameter constant="true" id="LMk2" metaid="COPASI33" name="LMk2" value="1.00144927536232E4">
<annotation>
<COPASI xmlns="http://www.copasi.org/static/sbml">
<rdf:RDF xmlns:dcterms="http://purl.org/dc/terms/" xmlns:rdf="http://www.w3.org/1999/02/22-rdf-syntax-ns#">
<rdf:Description rdf:about="#COPASI33">
<dcterms:created>
<rdf:Description>
<dcterms:W3CDTF>2014-07-02T13:32:36Z</dcterms:W3CDTF>
</rdf:Description>
</dcterms:created>
</rdf:Description>
</rdf:RDF>
</COPASI>
</annotation>
</parameter>
<parameter constant="true" id="MLk3" metaid="COPASI34" name="MLk3" value="1.31339255365637E4">
<annotation>
<COPASI xmlns="http://www.copasi.org/static/sbml">
<rdf:RDF xmlns:dcterms="http://purl.org/dc/terms/" xmlns:rdf="http://www.w3.org/1999/02/22-rdf-syntax-ns#">
<rdf:Description rdf:about="#COPASI34">
<dcterms:created>
<rdf:Description>
<dcterms:W3CDTF>2014-07-02T13:27:19Z</dcterms:W3CDTF>
</rdf:Description>
</dcterms:created>
</rdf:Description>
</rdf:RDF>
</COPASI>
</annotation>
</parameter>
<parameter constant="true" id="LMk3" metaid="COPASI35" name="LMk3" value="2630.59204225087">
<annotation>
<COPASI xmlns="http://www.copasi.org/static/sbml">
<rdf:RDF xmlns:dcterms="http://purl.org/dc/terms/" xmlns:rdf="http://www.w3.org/1999/02/22-rdf-syntax-ns#">
<rdf:Description rdf:about="#COPASI35">
<dcterms:created>
<rdf:Description>
<dcterms:W3CDTF>2014-07-02T13:31:47Z</dcterms:W3CDTF>
</rdf:Description>
</dcterms:created>