- Author:
- Hanne <Hanne@hanne-nielsens-macbook.local>
- Date:
- 2009-12-14 15:04:51+13:00
- Desc:
- Added images in ai and svg fomrat, removed non pub med referernces
- Permanent Source URI:
- https://staging.physiomeproject.org/workspace/saftenku_williams_sitsapesan_2001/rawfile/01e0dd22ef2f48c5e41ac8cdb544c2e224833d64/saftenku_williams_sitsapesan_2001_low_model.cellml
<?xml version='1.0' encoding='utf-8'?>
<!-- FILE : saftenku_low_model_2001_version02.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#" name="saftenku_williams_sitsapesan_2001_version03" cmeta:id="saftenku_low_model_2001_version02">
<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>Bioengineering Institute, University of Auckland</shortaffil>
</affiliation>
</author>
</articleinfo>
<section id="sec_status">
<title>Model Status</title>
<para>
This model has been recoded to remove the reaction elements by Catherine Lloyd. This file represents the 'low' Markovian model of the RyR channel activity. This file is known to load and run in PCEnv, but the output of the model may not be correct. Unfortunately, there is not enough information in the original paper to fully replicate this model.
</para>
</section>
<sect1 id="sec_structure">
<title>Model Structure</title>
<para>
In cardiac cells, Ca<superscript>2+</superscript> influx through L-type Ca<superscript>2+</superscript>-channels triggers the opening of ryanodine receptor (RyR) channels, thereby releasing Ca<superscript>2+</superscript> from the sarcoplasmic reticulum (SR) causing muscle contraction. The mechanisms underlying Ca<superscript>2+</superscript> activation and inactivation of RyR channels have been extensively studied. In their 2001 paper, Elena Saftenku, Alan J. Williams and Rebecca Sitsapesan found that the gating of RyR channels spontaneously shifts between high (H) and low (L) levels of activity and that there is evidence for multiple gating modes within H activity (H1 and H2). They propose distinct kinetic schemes for L, H1, and H2 activity that describe the major features of cardiac RyR channel gating (see the figure below).
</para>
<para>
The complete 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">
<unit units="mole" prefix="micro"/>
<unit units="litre" exponent="-1"/>
</units>
<units name="first_order_rate_constant">
<unit units="second" exponent="-1"/>
</units>
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<map_variables variable_2="C4O2" variable_1="C4O2"/>
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</connection>
<rdf:RDF>
<rdf:Bag rdf:about="rdf:#9b046b3d-e2df-4b41-aa47-b4e433c842d0">
<rdf:li>calcium dynamics</rdf:li>
<rdf:li>ryanodine receptor</rdf:li>
<rdf:li>signal transduction</rdf:li>
<rdf:li>cardiac myocyte</rdf:li>
<rdf:li>Cardiac Myocyte</rdf:li>
<rdf:li>cardiac</rdf:li>
<rdf:li>ryanodine receptors</rdf:li>
</rdf:Bag>
<rdf:Seq rdf:about="rdf:#0df67349-4584-41ca-91f3-5dedd13c91b8">
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<dcterms:W3CDTF>2007-08-21T10:50:06+12:00</dcterms:W3CDTF>
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<dcterms:W3CDTF>2007-05-25T00:00:00+00:00</dcterms:W3CDTF>
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<vCard:Given>James</vCard:Given>
<vCard:Family>Lawson</vCard:Family>
<vCard:Other>Richard</vCard:Other>
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<rdf:Description rdf:about="rdf:#29b80e5e-bbf0-4df6-b037-87e14dde96be">
<dcterms:modified rdf:resource="rdf:#db0e7869-ff84-49df-b14d-dd2904357b86"/>
<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>
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<rdf:value>c.lloyd@auckland.ac.nz</rdf:value>
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<vCard:Given>Rebecca</vCard:Given>
<vCard:Family>Sitsapesan</vCard:Family>
</rdf:Description>
<rdf:Description rdf:about="rdf:#986355fb-175a-470c-a3da-fd91248613d1">
<vCard:Orgname>The University of Auckland</vCard:Orgname>
<vCard:Orgunit>The Bioengineering Institute</vCard:Orgunit>
</rdf:Description>
<rdf:Description rdf:about="rdf:#2141fdf3-ffed-485b-a571-6f5f1834d692">
<vCard:Given>Catherine</vCard:Given>
<vCard:Family>Lloyd</vCard:Family>
<vCard:Other>May</vCard:Other>
</rdf:Description>
<rdf:Description rdf:about="rdf:#7e6ec5d6-0bce-4f5f-a773-3168c81714ae">
<bqs:Pubmed_id>11371448</bqs:Pubmed_id>
<bqs:JournalArticle rdf:resource="rdf:#f6cf8460-0558-426f-a193-9249d504802f"/>
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<dc:creator rdf:resource="rdf:#0df67349-4584-41ca-91f3-5dedd13c91b8"/>
<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:#1c2eb015-dfe9-4726-aca3-e92ab4a530b9"/>
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<bqs:last_page>2741</bqs:last_page>
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<bqs:subject_type>keyword</bqs:subject_type>
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</rdf:Description>
<rdf:Description rdf:about="rdf:#1c2eb015-dfe9-4726-aca3-e92ab4a530b9">
<dc:title>Biophysical Journal</dc:title>
</rdf:Description>
<rdf:Description rdf:about="rdf:#b7c55023-1ac2-4200-b920-1b89fdc70b70">
<dc:creator rdf:resource="rdf:#47096f45-1594-4d4c-87da-b399ce37a1dc"/>
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<rdf:Description rdf:about="rdf:#1ac5704e-212e-49c0-b431-5e454f66270c">
<vCard:FN>Catherine Lloyd</vCard:FN>
</rdf:Description>
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<dcterms:W3CDTF>2007-06-05T10:42:08+12:00</dcterms:W3CDTF>
</rdf:Description>
<rdf:Description rdf:about="#saftenku_low_model_2001_version02">
<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:#cc18644f-7ded-40bd-b754-78bbe9eab5a8"/>
<bqs:reference rdf:resource="rdf:#5f808d9e-7bb4-4482-b443-59580e40b565"/>
<bqs:reference rdf:resource="rdf:#7e6ec5d6-0bce-4f5f-a773-3168c81714ae"/>
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<rdf:Description rdf:about="rdf:#1f318789-73bc-4b2f-b833-a763970d6188">
<vCard:Given>Elena</vCard:Given>
<vCard:Family>Saftenku</vCard:Family>
</rdf:Description>
<rdf:Description rdf:about="rdf:#010de219-caa0-46b5-8724-66ba4bdd52ea">
<vCard:N rdf:resource="rdf:#253586ff-acc7-4a3c-9fad-dc94e33db4fe"/>
</rdf:Description>
<rdf:Description rdf:about="rdf:#e2a41ec0-8c3f-4d45-aaaf-1e911de22a84">
<vCard:ORG rdf:resource="rdf:#986355fb-175a-470c-a3da-fd91248613d1"/>
<vCard:EMAIL rdf:resource="rdf:#f91b2aa5-4201-4f79-8006-0c0b56cf15d9"/>
<vCard:N rdf:resource="rdf:#cefeea86-d702-4232-8b89-a16c1203d5b8"/>
</rdf:Description>
<rdf:Description rdf:about="rdf:#41cd4b18-b9c5-469c-b4ae-33c63f06178c">
<dcterms:modified rdf:resource="rdf:#5281f64e-4b77-45c8-87cb-ecf93eec3556"/>
<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:#010de219-caa0-46b5-8724-66ba4bdd52ea"/>
</rdf:Description>
<rdf:Description rdf:about="rdf:#cc18644f-7ded-40bd-b754-78bbe9eab5a8">
<dc:creator rdf:resource="rdf:#1ac5704e-212e-49c0-b431-5e454f66270c"/>
<rdf:value>This is the CellML description of Saftenku et al's 2001 markovian model of low activity levels of cardiac ryanodine receptors.
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>
</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="#C5">
<dcterms:alternative>closed state 5</dcterms:alternative>
<dc:title>C5</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="rdf:#ab5cda8c-3c35-47e7-86bb-ab3f4155c635">
<vCard:Given>Alan</vCard:Given>
<vCard:Family>Williams</vCard:Family>
<vCard:Other>J</vCard:Other>
</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="">
<dc:publisher>The University of Auckland, Bioengineering Institute</dc:publisher>
<cmeta:comment rdf:resource="rdf:#b7c55023-1ac2-4200-b920-1b89fdc70b70"/>
<dcterms:created rdf:resource="rdf:#ca761942-6aa7-48db-b5a8-78a716cc5211"/>
<dc:creator rdf:resource="rdf:#e2a41ec0-8c3f-4d45-aaaf-1e911de22a84"/>
<cmeta:modification rdf:resource="rdf:#41cd4b18-b9c5-469c-b4ae-33c63f06178c"/>
<cmeta:modification rdf:resource="rdf:#29b80e5e-bbf0-4df6-b037-87e14dde96be"/>
</rdf:Description>
<rdf:Description rdf:about="rdf:#20d04ea1-6474-4187-899e-394b778a725f">
<rdf:type rdf:resource="http://www.cellml.org/bqs/1.0#Person"/>
<vCard:N rdf:resource="rdf:#1f318789-73bc-4b2f-b833-a763970d6188"/>
</rdf:Description>
<rdf:Description rdf:about="rdf:#2053e194-cdfe-48bf-98c4-daed1cda8123">
<vCard:N rdf:resource="rdf:#2141fdf3-ffed-485b-a571-6f5f1834d692"/>
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<rdf:Description rdf:about="rdf:#5f808d9e-7bb4-4482-b443-59580e40b565">
<dc:subject rdf:resource="rdf:#a276f149-0b51-40fe-a255-1f8d0138c909"/>
</rdf:Description>
<rdf:Description rdf:about="rdf:#cefeea86-d702-4232-8b89-a16c1203d5b8">
<vCard:Given>Catherine</vCard:Given>
<vCard:Family>Lloyd</vCard:Family>
<vCard:Other>May</vCard:Other>
</rdf:Description>
<rdf:Description rdf:about="rdf:#357316d1-a18c-4d5e-9434-162c51507145">
<dcterms:W3CDTF>2001-06</dcterms:W3CDTF>
</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="#O3">
<dcterms:alternative>open state 3</dcterms:alternative>
<dc:title>O3</dc:title>
</rdf:Description>
<rdf:Description rdf:about="#O1">
<dcterms:alternative>open state 1</dcterms:alternative>
<dc:title>O1</dc:title>
</rdf:Description>
</rdf:RDF>
</model>
