<?xml version='1.0' encoding='utf-8'?>
<!-- FILE : saftenku_H1_model_2001.xml
CREATED : 25th May 2007
LAST MODIFIED : 25th May 2007
AUTHOR : Catherine Lloyd
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 Saftenku et al's
2001 markovian model of low activity levels of cardiac ryanodine receptors.
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:dcterms="http://purl.org/dc/terms/" xmlns:vCard="http://www.w3.org/2001/vcard-rdf/3.0#" cmeta:id="saftenku_H1_model_2001" name="saftenku_2001">
<documentation xmlns="http://cellml.org/tmp-documentation">
<article>
<articleinfo>
<title>Markovian Models of Low and High Activity Levels of Cardiac Ryanodine Receptors</title>
<author>
<firstname>Catherine</firstname>
<surname>Lloyd</surname>
<affiliation>
<shortaffil>Auckland Bioengineering Institute, University of Auckland</shortaffil>
</affiliation>
</author>
</articleinfo>
<section id="sec_status">
<title>Model Status</title>
<para>
This CellML model represents the 'H1' Markovian model of the RyR channel activity. The model runs in both OpenCell and COR and the units are consistent. Unfortunately, there are no comparable figures in the published paper for a curation check of the CellML model results.
</para>
</section>
<sect1 id="sec_structure">
<title>Model Structure</title>
<para>
ABSTRACT: The modal gating behavior of single sheep cardiac sarcoplasmic reticulum (SR) Ca2+-release/ryanodine receptor (RyR) channels was assessed. We find that the gating of RyR channels spontaneously shifts between high (H) and low (L) levels of activity and inactive periods where no channel openings are detected (I). Moreover, we find that there is evidence for multiple gating modes within H activity, which we term H1 and H2 mode. Our results demonstrate that the underlying mechanisms regulating gating are similar in native and purified channels. Dwell-time distributions of L activity were best fitted by three open and five closed significant exponential components whereas dwell-time distributions of H1 activity were best fitted by two to three open and four closed significant exponential components. Increases in cytosolic [Ca2+] cause an increase in open probability (Po) within L activity and an increase in the probability of occurrence of H activity. Open lifetime distributions within L activity were Ca2+ independent whereas open lifetime distributions within H activity were Ca2+ dependent. This study is the first attempt to estimate RyR single-channel kinetic parameters from sequences of idealized dwell-times and to develop kinetic models of RyR gating using the criterion of maximum likelihood. We propose distinct kinetic schemes for L, H1, and H2 activity that describe the major features of sheep cardiac RyR channel gating at these levels of activity.
</para>
<para>
The original paper reference is cited below:
</para>
<para>
Markovian Models Of Low And High Activity Levels Of Cardiac Ryanodine Receptors, Elena Saftenku, Alan J. Williams and Rebecca Sitsapesan, 2001, <emphasis>Biophysical Journal</emphasis>, 80, 2727-2741. <ulink url="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=11371448&dopt=Abstract">PubMed ID: 11371448</ulink> </para>
<informalfigure float="0" id="fig_reaction_diagrams">
<mediaobject>
<imageobject>
<objectinfo>
<title>Schematic diagrams of the RyR models</title>
</objectinfo>
<imagedata fileref="saftenku_2001.png"/>
</imageobject>
</mediaobject>
<caption>Kinetic models of the gating of cardiac ryanodine receptors at low and high levels of activity.</caption>
</informalfigure>
</sect1>
</article>
</documentation>
<units name="micromolar">
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<unit units="litre" exponent="-1"/>
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<units name="first_order_rate_constant">
<unit units="second" exponent="-1"/>
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<units name="second_order_rate_constant">
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<rdf:RDF>
<rdf:Bag rdf:about="rdf:#ad2065e5-8cf1-478c-9e56-ecc2b1188a87">
<rdf:li>Cardiac Myocyte</rdf:li>
<rdf:li>calcium dynamics</rdf:li>
<rdf:li>ryanodine receptors</rdf:li>
</rdf:Bag>
<rdf:Seq rdf:about="rdf:#d51086a3-08b5-43fc-8597-45195486c90d">
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<rdf:li rdf:resource="rdf:#db54a206-7907-47dc-8cdc-e4822bb6b803"/>
</rdf:Seq>
<rdf:Description rdf:about="rdf:#ddae8a0f-9ce1-4c6e-b47d-76784ffdcd5f">
<dc:subject rdf:resource="rdf:#9d35364a-f1c3-4060-9cb1-d1d949020a90"/>
</rdf:Description>
<rdf:Description rdf:about="rdf:#597c4aa1-beb2-436b-98da-318f8f39ac92">
<vCard:Given>Catherine</vCard:Given>
<vCard:Family>Lloyd</vCard:Family>
<vCard:Other>May</vCard:Other>
</rdf:Description>
<rdf:Description rdf:about="rdf:#20a01b9d-4c7c-4b0b-88d3-4c5e6301d55d">
<vCard:N rdf:resource="rdf:#bff6ecc4-4975-496c-b242-022af45b47df"/>
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<rdf:Description rdf:about="rdf:#a9557817-9a0c-463e-b870-dd5ea36de5bc">
<vCard:Given>Alan</vCard:Given>
<vCard:Family>Williams</vCard:Family>
<vCard:Other>J</vCard:Other>
</rdf:Description>
<rdf:Description rdf:about="rdf:#8b32001f-f6bf-4cac-b827-be8b81f8aecf">
<bqs:Pubmed_id>11371448</bqs:Pubmed_id>
<bqs:JournalArticle rdf:resource="rdf:#20457224-dbf6-4279-8db2-300c42e68d4f"/>
</rdf:Description>
<rdf:Description rdf:about="rdf:#9d35364a-f1c3-4060-9cb1-d1d949020a90">
<bqs:subject_type>keyword</bqs:subject_type>
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<rdf:Description rdf:about="rdf:#e9eb9f03-a1d5-4c91-a916-98ef4f4fec7e">
<vCard:Given>Elena</vCard:Given>
<vCard:Family>Saftenku</vCard:Family>
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<dc:creator rdf:resource="rdf:#0c2c081c-513a-4205-9fc2-483d6da9ddef"/>
<rdf:value>This is the CellML description of Saftenku et al's 2001 markovian
model of low activity levels of cardiac ryanodine receptors.</rdf:value>
</rdf:Description>
<rdf:Description rdf:about="rdf:#ded3fd93-4613-4002-b144-2e20422bb84e">
<dc:title>Biophysical Journal</dc:title>
</rdf:Description>
<rdf:Description rdf:about="rdf:#bff6ecc4-4975-496c-b242-022af45b47df">
<vCard:Given>Catherine</vCard:Given>
<vCard:Family>Lloyd</vCard:Family>
<vCard:Other>May</vCard:Other>
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<rdf:Description rdf:about="rdf:#63490779-8ebd-4055-a7ce-e848d312633d">
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<vCard:ORG rdf:resource="rdf:#cdab5d46-ef24-456d-a551-33b7e8a0ff21"/>
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<rdf:Description rdf:about="rdf:#cdab5d46-ef24-456d-a551-33b7e8a0ff21">
<vCard:Orgname>The University of Auckland</vCard:Orgname>
<vCard:Orgunit>The Bioengineering Institute</vCard:Orgunit>
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<rdf:Description rdf:about="rdf:#6c9837c0-c323-4131-9fc8-20f25f20bea5">
<dcterms:modified rdf:resource="rdf:#6c92080a-da75-49f4-be21-1c7b94b03498"/>
<rdf:value>Gave C1 an initial value of 1.0 - this allows the model to produce a curve, rather than a flat line output. This is still unlikely to be the correct output as the model is supposed to depend on voltage and changing calcium levels.</rdf:value>
<cmeta:modifier rdf:resource="rdf:#2af888ce-2cff-499f-9bea-ad2f63e43a54"/>
</rdf:Description>
<rdf:Description rdf:about="">
<dc:title>Markovian Models of Low and High Activity Levals of Cardiac Ryanodine Receptors (H1 Model)</dc:title>
<dc:publisher>The University of Auckland, Bioengineering Institute</dc:publisher>
<cmeta:comment rdf:resource="rdf:#2cbe538e-af80-43b0-8404-b3c9b701e8de"/>
<dcterms:created rdf:resource="rdf:#9bf81160-fd30-4021-8381-2502df647c4c"/>
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<cmeta:modification rdf:resource="rdf:#3d131d26-f88c-462d-9007-213077a073b4"/>
</rdf:Description>
<rdf:Description rdf:about="#saftenku_H1_model_2001">
<dc:title>
Saftenku et al's 2001 markovian model of low activity levels of cardiac ryanodine receptors.
</dc:title>
<cmeta:bio_entity>Cardiac Myocyte</cmeta:bio_entity>
<cmeta:comment rdf:resource="rdf:#b3d3d804-2ab4-4090-9ccc-d2fb78bf50c9"/>
<bqs:reference rdf:resource="rdf:#8b32001f-f6bf-4cac-b827-be8b81f8aecf"/>
<bqs:reference rdf:resource="rdf:#ddae8a0f-9ce1-4c6e-b47d-76784ffdcd5f"/>
</rdf:Description>
<rdf:Description rdf:about="rdf:#887c6a74-bdf0-41b5-bbc6-0fcaf0bf314d">
<dcterms:W3CDTF>2001-06</dcterms:W3CDTF>
</rdf:Description>
<rdf:Description rdf:about="rdf:#e0812e2a-070d-4abd-97a4-331d96cd4486">
<vCard:Given>James</vCard:Given>
<vCard:Family>Lawson</vCard:Family>
<vCard:Other>Richard</vCard:Other>
</rdf:Description>
<rdf:Description rdf:about="rdf:#9bf81160-fd30-4021-8381-2502df647c4c">
<dcterms:W3CDTF>2007-05-25T00:00:00+00:00</dcterms:W3CDTF>
</rdf:Description>
<rdf:Description rdf:about="rdf:#db54a206-7907-47dc-8cdc-e4822bb6b803">
<rdf:type rdf:resource="http://www.cellml.org/bqs/1.0#Person"/>
<vCard:N rdf:resource="rdf:#daa760f3-4764-4eeb-8fb5-079736745793"/>
</rdf:Description>
<rdf:Description rdf:about="rdf:#460dceb6-1397-4456-973c-3d4808d41bcc">
<dcterms:W3CDTF>2007-06-05T10:43:32+12:00</dcterms:W3CDTF>
</rdf:Description>
<rdf:Description rdf:about="rdf:#daa760f3-4764-4eeb-8fb5-079736745793">
<vCard:Given>Rebecca</vCard:Given>
<vCard:Family>Sitsapesan</vCard:Family>
</rdf:Description>
<rdf:Description rdf:about="rdf:#2cbe538e-af80-43b0-8404-b3c9b701e8de">
<dc:creator rdf:resource="rdf:#e155e669-cc65-41c3-8866-3545e9d4c7d8"/>
</rdf:Description>
<rdf:Description rdf:about="#C4">
<dcterms:alternative>closed state 4</dcterms:alternative>
<dc:title>C4</dc:title>
</rdf:Description>
<rdf:Description rdf:about="#C2">
<dcterms:alternative>closed state 2</dcterms:alternative>
<dc:title>C2</dc:title>
</rdf:Description>
<rdf:Description rdf:about="#C3">
<dcterms:alternative>closed state 3</dcterms:alternative>
<dc:title>C3</dc:title>
</rdf:Description>
<rdf:Description rdf:about="#C1">
<dcterms:alternative>closed state 1</dcterms:alternative>
<dc:title>C1</dc:title>
</rdf:Description>
<rdf:Description rdf:about="#O1">
<dcterms:alternative>open state 1</dcterms:alternative>
<dc:title>O1</dc:title>
</rdf:Description>
<rdf:Description rdf:about="rdf:#2af888ce-2cff-499f-9bea-ad2f63e43a54">
<vCard:N rdf:resource="rdf:#e0812e2a-070d-4abd-97a4-331d96cd4486"/>
</rdf:Description>
<rdf:Description rdf:about="rdf:#6c92080a-da75-49f4-be21-1c7b94b03498">
<dcterms:W3CDTF>2007-08-21T10:20:13+12:00</dcterms:W3CDTF>
</rdf:Description>
<rdf:Description rdf:about="rdf:#20457224-dbf6-4279-8db2-300c42e68d4f">
<dc:creator rdf:resource="rdf:#d51086a3-08b5-43fc-8597-45195486c90d"/>
<dc:title>Markovian Models of Low and High Activity Levals of Cardiac Ryanodine Receptors</dc:title>
<bqs:volume>80</bqs:volume>
<bqs:first_page>2727</bqs:first_page>
<bqs:Journal rdf:resource="rdf:#ded3fd93-4613-4002-b144-2e20422bb84e"/>
<dcterms:issued rdf:resource="rdf:#887c6a74-bdf0-41b5-bbc6-0fcaf0bf314d"/>
<bqs:last_page>2741</bqs:last_page>
</rdf:Description>
<rdf:Description rdf:about="rdf:#0c2c081c-513a-4205-9fc2-483d6da9ddef">
<vCard:FN>Catherine Lloyd</vCard:FN>
</rdf:Description>
<rdf:Description rdf:about="#O2">
<dcterms:alternative>open state 2</dcterms:alternative>
<dc:title>O2</dc:title>
</rdf:Description>
<rdf:Description rdf:about="rdf:#1680fa87-8165-4302-bda8-ff95781b1ef0">
<rdf:type rdf:resource="http://imc.org/vCard/3.0#internet"/>
<rdf:value>c.lloyd@auckland.ac.nz</rdf:value>
</rdf:Description>
<rdf:Description rdf:about="rdf:#3d131d26-f88c-462d-9007-213077a073b4">
<dcterms:modified rdf:resource="rdf:#460dceb6-1397-4456-973c-3d4808d41bcc"/>
<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>
<cmeta:modifier rdf:resource="rdf:#20a01b9d-4c7c-4b0b-88d3-4c5e6301d55d"/>
</rdf:Description>
<rdf:Description rdf:about="rdf:#2a7f73f0-6a73-43e2-a091-46a4917c2d91">
<rdf:type rdf:resource="http://www.cellml.org/bqs/1.0#Person"/>
<vCard:N rdf:resource="rdf:#a9557817-9a0c-463e-b870-dd5ea36de5bc"/>
</rdf:Description>
</rdf:RDF>
</model>
