- Author:
- pmr2.import <nobody@models.cellml.org>
- Date:
- 2006-09-04 00:25:49+12:00
- Desc:
- committing version01 of saftenku_williams_sitsapesan_2001
- Permanent Source URI:
- http://models.cellml.org/workspace/saftenku_williams_sitsapesan_2001/rawfile/2f2475b51d7a8c2662aa6acbb3b3912d9576d457/saftenku_williams_sitsapesan_2001_H1_model.cellml
<?xml version='1.0' encoding='utf-8'?>
<!-- FILE : saftenku_H1_model_2001.xml
CREATED : 22nd March 2002
LAST MODIFIED : 9th April 2003
AUTHOR : Catherine Lloyd
Bioengineering Institute
The University of Auckland
MODEL STATUS : This model conforms to the CellML 1.0 Specification released on
10th August 2001, and the 16/1/02 CellML Metadata 1.0 Specification.
DESCRIPTION : This file contains a CellML description of Saftenku et al's
2001 markovian model of high activity levels of cardiac ryanodine receptors.
CHANGES:
18/07/2002 - CML - Added more metadata.
09/04/2003 - AAC - Added publication date information.
--><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:cellml="http://www.cellml.org/cellml/1.0#" xmlns:dcterms="http://purl.org/dc/terms/" xmlns:vCard="http://www.w3.org/2001/vcard-rdf/3.0#" cmeta:id="saftenku_williams_sitsapesan_2001_version01" name="saftenku_williams_sitsapesan_2001_version01">
<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 is the original unchecked version of the model imported from the previous
CellML model repository, 24-Jan-2006.
</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 <xref linkend="fig_reaction_diagrams"/> below).
</para>
<para>
The complete original paper reference is cited below:
</para>
<para>
<ulink url="http://www.biophysj.org/cgi/content/abstract/80/6/2727">Markovian Models Of Low And High Activity Levels Of Cardiac Ryanodine Receptors</ulink>, Elena Saftenku, Alan J. Williams and Rebecca Sitsapesan, 2001, <ulink url="http://www.biophysj.org/">
<emphasis>Biophysical Journal</emphasis>
</ulink>, 80, 2727-2741. (<ulink url="http://www.biophysj.org/cgi/content/full/80/6/2727">Full text</ulink> and <ulink url="http://www.biophysj.org/cgi/reprint/80/6/2727.pdf">PDF versions</ulink> of the article are available to subscribers on the Biophysical Journal website.) <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>
<para>
The raw CellML descriptions of the markovian models of low and high activity levels of cardiac ryanodine receptors can be downloaded in various formats as described in <xref linkend="sec_download_this_model"/>.
</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>
<!--
Below, we define some additional units for association with variables and
constants within the model. The identifiers are fairly self-explanatory.
-->
<units name="micromolar">
<unit units="mole" prefix="micro"/>
<unit units="litre" exponent="-1"/>
</units>
<units name="flux">
<unit units="micromolar"/>
<unit units="second" exponent="-1"/>
</units>
<units name="first_order_rate_constant">
<unit units="second" exponent="-1"/>
</units>
<units name="second_order_rate_constant">
<unit units="micromolar" exponent="-1"/>
<unit units="second" exponent="-1"/>
</units>
<!--
The "environment" component is used to declare variables that are used by
all or most of the other components, in this case just "time".
-->
<component name="environment">
<variable units="second" public_interface="out" name="time"/>
</component>
<!--
The following components describe all the reactants and products involved in
reactions.
-->
<component cmeta:id="C1" name="C1">
<variable units="micromolar" public_interface="out" name="C1"/>
<variable units="flux" public_interface="in" name="delta_C1_rxn_1"/>
<variable units="second" public_interface="in" name="time"/>
<math xmlns="http://www.w3.org/1998/Math/MathML">
<apply>
<eq/>
<apply>
<diff/>
<bvar>
<ci>time</ci>
</bvar>
<ci>C1</ci>
</apply>
<ci>delta_C1_rxn_1</ci>
</apply>
</math>
</component>
<component cmeta:id="C2" name="C2">
<variable units="micromolar" public_interface="out" name="C2"/>
<variable units="flux" public_interface="in" name="delta_C2_rxn_1"/>
<variable units="flux" public_interface="in" name="delta_C2_rxn_2"/>
<variable units="flux" public_interface="in" name="delta_C2_rxn_5"/>
<variable units="second" public_interface="in" name="time"/>
<math xmlns="http://www.w3.org/1998/Math/MathML">
<apply>
<eq/>
<apply>
<diff/>
<bvar>
<ci>time</ci>
</bvar>
<ci>C2</ci>
</apply>
<apply>
<plus/>
<ci>delta_C2_rxn_1</ci>
<ci>delta_C2_rxn_2</ci>
<ci>delta_C2_rxn_5</ci>
</apply>
</apply>
</math>
</component>
<component cmeta:id="C3" name="C3">
<variable units="micromolar" public_interface="out" name="C3"/>
<variable units="flux" public_interface="in" name="delta_C3_rxn_2"/>
<variable units="flux" public_interface="in" name="delta_C3_rxn_3"/>
<variable units="second" public_interface="in" name="time"/>
<math xmlns="http://www.w3.org/1998/Math/MathML">
<apply>
<eq/>
<apply>
<diff/>
<bvar>
<ci>time</ci>
</bvar>
<ci>C3</ci>
</apply>
<apply>
<plus/>
<ci>delta_C3_rxn_2</ci>
<ci>delta_C3_rxn_3</ci>
</apply>
</apply>
</math>
</component>
<component cmeta:id="C4" name="C4">
<variable units="micromolar" public_interface="out" name="C4"/>
<variable units="flux" public_interface="in" name="delta_C4_rxn_4"/>
<variable units="second" public_interface="in" name="time"/>
<math xmlns="http://www.w3.org/1998/Math/MathML">
<apply>
<eq/>
<apply>
<diff/>
<bvar>
<ci>time</ci>
</bvar>
<ci>C4</ci>
</apply>
<ci>delta_C4_rxn_4</ci>
</apply>
</math>
</component>
<component cmeta:id="O1" name="O1">
<variable units="micromolar" public_interface="out" name="O1"/>
<variable units="flux" public_interface="in" name="delta_O1_rxn_5"/>
<variable units="second" public_interface="in" name="time"/>
<math xmlns="http://www.w3.org/1998/Math/MathML">
<apply>
<eq/>
<apply>
<diff/>
<bvar>
<ci>time</ci>
</bvar>
<ci>O1</ci>
</apply>
<ci>delta_O1_rxn_5</ci>
</apply>
</math>
</component>
<component cmeta:id="O2" name="O2">
<variable units="micromolar" public_interface="out" name="O2"/>
<variable units="flux" public_interface="in" name="delta_O2_rxn_3"/>
<variable units="flux" public_interface="in" name="delta_O2_rxn_4"/>
<variable units="second" public_interface="in" name="time"/>
<math xmlns="http://www.w3.org/1998/Math/MathML">
<apply>
<eq/>
<apply>
<diff/>
<bvar>
<ci>time</ci>
</bvar>
<ci>O2</ci>
</apply>
<apply>
<plus/>
<ci>delta_O2_rxn_3</ci>
<ci>delta_O2_rxn_4</ci>
</apply>
</apply>
</math>
</component>
<component cmeta:id="Ca" name="Ca">
<variable units="micromolar" public_interface="out" name="Ca"/>
<variable units="flux" public_interface="in" name="delta_Ca_rxn_1"/>
<variable units="flux" public_interface="in" name="delta_Ca_rxn_2"/>
<variable units="second" public_interface="in" name="time"/>
<math xmlns="http://www.w3.org/1998/Math/MathML">
<apply>
<eq/>
<apply>
<diff/>
<bvar>
<ci>time</ci>
</bvar>
<ci>Ca</ci>
</apply>
<apply>
<plus/>
<ci>delta_Ca_rxn_1</ci>
<ci>delta_Ca_rxn_2</ci>
</apply>
</apply>
</math>
</component>
<!--
The following components describe the reactions of the model.
-->
<component name="reaction1">
<variable units="micromolar" public_interface="in" name="Ca"/>
<variable units="micromolar" public_interface="in" name="C1"/>
<variable units="micromolar" public_interface="in" name="C2"/>
<variable units="second_order_rate_constant" name="k_C1C2" initial_value="3.26"/>
<variable units="first_order_rate_constant" name="k_C2C1" initial_value="116.0"/>
<variable units="flux" public_interface="out" name="delta_C1_rxn_1"/>
<variable units="flux" public_interface="out" name="delta_Ca_rxn_1"/>
<variable units="flux" public_interface="out" name="delta_C2_rxn_1"/>
<variable units="flux" name="r"/>
<reaction reversible="yes">
<variable_ref variable="C1">
<role stoichiometry="1" direction="forward" delta_variable="delta_C1_rxn_1" role="reactant"/>
</variable_ref>
<variable_ref variable="Ca">
<role stoichiometry="1" direction="forward" delta_variable="delta_Ca_rxn_1" role="reactant"/>
</variable_ref>
<variable_ref variable="C2">
<role stoichiometry="1" direction="forward" delta_variable="delta_C2_rxn_1" role="product"/>
</variable_ref>
<variable_ref variable="r">
<role role="rate">
<math xmlns="http://www.w3.org/1998/Math/MathML">
<apply>
<eq/>
<ci> r </ci>
<apply>
<plus/>
<apply>
<minus/>
<apply>
<times/>
<ci> k_C1C2 </ci>
<ci> C1 </ci>
<ci> Ca </ci>
</apply>
</apply>
<apply>
<times/>
<ci> k_C2C1 </ci>
<ci> C2 </ci>
</apply>
</apply>
</apply>
</math>
</role>
</variable_ref>
</reaction>
</component>
<component name="reaction2">
<variable units="micromolar" public_interface="in" name="Ca"/>
<variable units="micromolar" public_interface="in" name="C2"/>
<variable units="micromolar" public_interface="in" name="C3"/>
<variable units="second_order_rate_constant" name="k_C2C3" initial_value="0.66"/>
<variable units="first_order_rate_constant" name="k_C3C2" initial_value="163.0"/>
<variable units="flux" public_interface="out" name="delta_C2_rxn_2"/>
<variable units="flux" public_interface="out" name="delta_Ca_rxn_2"/>
<variable units="flux" public_interface="out" name="delta_C3_rxn_2"/>
<variable units="flux" name="r"/>
<reaction reversible="yes">
<variable_ref variable="C2">
<role stoichiometry="1" direction="forward" delta_variable="delta_C2_rxn_2" role="reactant"/>
</variable_ref>
<variable_ref variable="Ca">
<role stoichiometry="1" direction="forward" delta_variable="delta_Ca_rxn_2" role="reactant"/>
</variable_ref>
<variable_ref variable="C3">
<role stoichiometry="1" direction="forward" delta_variable="delta_C3_rxn_2" role="product"/>
</variable_ref>
<variable_ref variable="r">
<role role="rate">
<math xmlns="http://www.w3.org/1998/Math/MathML">
<apply>
<eq/>
<ci> r </ci>
<apply>
<plus/>
<apply>
<minus/>
<apply>
<times/>
<ci> k_C2C3 </ci>
<ci> C2 </ci>
<ci> Ca </ci>
</apply>
</apply>
<apply>
<times/>
<ci> k_C3C2 </ci>
<ci> C3 </ci>
</apply>
</apply>
</apply>
</math>
</role>
</variable_ref>
</reaction>
</component>
<component name="reaction3">
<variable units="micromolar" public_interface="in" name="C3"/>
<variable units="micromolar" public_interface="in" name="O2"/>
<variable units="first_order_rate_constant" name="k_C3O2" initial_value="7.77"/>
<variable units="first_order_rate_constant" name="k_O2C3" initial_value="330.0"/>
<variable units="flux" public_interface="out" name="delta_C3_rxn_3"/>
<variable units="flux" public_interface="out" name="delta_O2_rxn_3"/>
<variable units="flux" name="r"/>
<reaction reversible="yes">
<variable_ref variable="C3">
<role stoichiometry="1" direction="forward" delta_variable="delta_C3_rxn_3" role="reactant"/>
</variable_ref>
<variable_ref variable="O2">
<role stoichiometry="1" direction="forward" delta_variable="delta_O2_rxn_3" role="product"/>
</variable_ref>
<variable_ref variable="r">
<role role="rate">
<math xmlns="http://www.w3.org/1998/Math/MathML">
<apply>
<eq/>
<ci> r </ci>
<apply>
<plus/>
<apply>
<minus/>
<apply>
<times/>
<ci> k_C3O2 </ci>
<ci> C3 </ci>
</apply>
</apply>
<apply>
<times/>
<ci> k_O2C3 </ci>
<ci> O2 </ci>
</apply>
</apply>
</apply>
</math>
</role>
</variable_ref>
</reaction>
</component>
<component name="reaction4">
<variable units="micromolar" public_interface="in" name="O2"/>
<variable units="micromolar" public_interface="in" name="C4"/>
<variable units="first_order_rate_constant" name="k_O2C4" initial_value="298.0"/>
<variable units="first_order_rate_constant" name="k_C4O2" initial_value="2390.0"/>
<variable units="flux" public_interface="out" name="delta_O2_rxn_4"/>
<variable units="flux" public_interface="out" name="delta_C4_rxn_4"/>
<variable units="flux" name="r"/>
<reaction reversible="yes">
<variable_ref variable="O2">
<role stoichiometry="1" direction="forward" delta_variable="delta_O2_rxn_4" role="reactant"/>
</variable_ref>
<variable_ref variable="C4">
<role stoichiometry="1" direction="forward" delta_variable="delta_C4_rxn_4" role="product"/>
</variable_ref>
<variable_ref variable="r">
<role role="rate">
<math xmlns="http://www.w3.org/1998/Math/MathML">
<apply>
<eq/>
<ci> r </ci>
<apply>
<plus/>
<apply>
<minus/>
<apply>
<times/>
<ci> k_O2C4 </ci>
<ci> O2 </ci>
</apply>
</apply>
<apply>
<times/>
<ci> k_C4O2 </ci>
<ci> C4 </ci>
</apply>
</apply>
</apply>
</math>
</role>
</variable_ref>
</reaction>
</component>
<component name="reaction5">
<variable units="micromolar" public_interface="in" name="C2"/>
<variable units="micromolar" public_interface="in" name="O1"/>
<variable units="first_order_rate_constant" name="k_C2O1" initial_value="7.86"/>
<variable units="first_order_rate_constant" name="k_O1C2" initial_value="1480.0"/>
<variable units="flux" public_interface="out" name="delta_C2_rxn_5"/>
<variable units="flux" public_interface="out" name="delta_O1_rxn_5"/>
<variable units="flux" name="r"/>
<reaction reversible="yes">
<variable_ref variable="C2">
<role stoichiometry="1" direction="forward" delta_variable="delta_C2_rxn_5" role="reactant"/>
</variable_ref>
<variable_ref variable="O1">
<role stoichiometry="1" direction="forward" delta_variable="delta_O1_rxn_5" role="product"/>
</variable_ref>
<variable_ref variable="r">
<role role="rate">
<math xmlns="http://www.w3.org/1998/Math/MathML">
<apply>
<eq/>
<ci> r </ci>
<apply>
<plus/>
<apply>
<minus/>
<apply>
<times/>
<ci> k_C2O1 </ci>
<ci> C2 </ci>
</apply>
</apply>
<apply>
<times/>
<ci> k_O1C2 </ci>
<ci> O1 </ci>
</apply>
</apply>
</apply>
</math>
</role>
</variable_ref>
</reaction>
</component>
<connection>
<map_components component_2="environment" component_1="C1"/>
<map_variables variable_2="time" variable_1="time"/>
</connection>
<connection>
<map_components component_2="environment" component_1="C2"/>
<map_variables variable_2="time" variable_1="time"/>
</connection>
<connection>
<map_components component_2="environment" component_1="C3"/>
<map_variables variable_2="time" variable_1="time"/>
</connection>
<connection>
<map_components component_2="environment" component_1="C4"/>
<map_variables variable_2="time" variable_1="time"/>
</connection>
<connection>
<map_components component_2="environment" component_1="O1"/>
<map_variables variable_2="time" variable_1="time"/>
</connection>
<connection>
<map_components component_2="environment" component_1="O2"/>
<map_variables variable_2="time" variable_1="time"/>
</connection>
<connection>
<map_components component_2="environment" component_1="Ca"/>
<map_variables variable_2="time" variable_1="time"/>
</connection>
<connection>
<map_components component_2="reaction1" component_1="C1"/>
<map_variables variable_2="C1" variable_1="C1"/>
<map_variables variable_2="delta_C1_rxn_1" variable_1="delta_C1_rxn_1"/>
</connection>
<connection>
<map_components component_2="reaction1" component_1="C2"/>
<map_variables variable_2="C2" variable_1="C2"/>
<map_variables variable_2="delta_C2_rxn_1" variable_1="delta_C2_rxn_1"/>
</connection>
<connection>
<map_components component_2="reaction2" component_1="C2"/>
<map_variables variable_2="C2" variable_1="C2"/>
<map_variables variable_2="delta_C2_rxn_2" variable_1="delta_C2_rxn_2"/>
</connection>
<connection>
<map_components component_2="reaction5" component_1="C2"/>
<map_variables variable_2="C2" variable_1="C2"/>
<map_variables variable_2="delta_C2_rxn_5" variable_1="delta_C2_rxn_5"/>
</connection>
<connection>
<map_components component_2="reaction2" component_1="C3"/>
<map_variables variable_2="C3" variable_1="C3"/>
<map_variables variable_2="delta_C3_rxn_2" variable_1="delta_C3_rxn_2"/>
</connection>
<connection>
<map_components component_2="reaction3" component_1="C3"/>
<map_variables variable_2="C3" variable_1="C3"/>
<map_variables variable_2="delta_C3_rxn_3" variable_1="delta_C3_rxn_3"/>
</connection>
<connection>
<map_components component_2="reaction4" component_1="C4"/>
<map_variables variable_2="C4" variable_1="C4"/>
<map_variables variable_2="delta_C4_rxn_4" variable_1="delta_C4_rxn_4"/>
</connection>
<connection>
<map_components component_2="reaction5" component_1="O1"/>
<map_variables variable_2="O1" variable_1="O1"/>
<map_variables variable_2="delta_O1_rxn_5" variable_1="delta_O1_rxn_5"/>
</connection>
<connection>
<map_components component_2="reaction3" component_1="O2"/>
<map_variables variable_2="O2" variable_1="O2"/>
<map_variables variable_2="delta_O2_rxn_3" variable_1="delta_O2_rxn_3"/>
</connection>
<connection>
<map_components component_2="reaction4" component_1="O2"/>
<map_variables variable_2="O2" variable_1="O2"/>
<map_variables variable_2="delta_O2_rxn_4" variable_1="delta_O2_rxn_4"/>
</connection>
<connection>
<map_components component_2="reaction1" component_1="Ca"/>
<map_variables variable_2="Ca" variable_1="Ca"/>
<map_variables variable_2="delta_Ca_rxn_1" variable_1="delta_Ca_rxn_1"/>
</connection>
<connection>
<map_components component_2="reaction2" component_1="Ca"/>
<map_variables variable_2="Ca" variable_1="Ca"/>
<map_variables variable_2="delta_Ca_rxn_2" variable_1="delta_Ca_rxn_2"/>
</connection>
<rdf:RDF>
<rdf:Bag rdf:about="rdf:#f1b93d14-4c78-4bc5-9520-d7903bc8e8fe">
<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:#citationAuthorsSeq">
<rdf:li rdf:resource="rdf:#author1Vcard"/>
<rdf:li rdf:resource="rdf:#author2Vcard"/>
<rdf:li rdf:resource="rdf:#author3Vcard"/>
</rdf:Seq>
<rdf:Description rdf:about="rdf:#author1VcardN">
<vCard:Given>Elena</vCard:Given>
<vCard:Family>Saftenku</vCard:Family>
</rdf:Description>
<rdf:Description rdf:about="rdf:#92c41e66-205d-4b4e-bc83-cde2a95439ff">
<vCard:Orgname>The University of Auckland</vCard:Orgname>
<vCard:Orgunit>The Bioengineering Institute</vCard:Orgunit>
</rdf:Description>
<rdf:Description rdf:about="rdf:#233a46b8-8279-4142-b422-1a979660fbfd">
<dcterms:W3CDTF>2002-03-22</dcterms:W3CDTF>
</rdf:Description>
<rdf:Description rdf:about="rdf:#a9d14403-f19f-481d-879c-e26ab48362d2">
<dc:creator rdf:resource="rdf:#citationAuthorsSeq"/>
<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:#d5a2c17e-11de-4b53-9022-674734bb07e6"/>
<dcterms:issued rdf:resource="rdf:#fb214e65-bad2-49ed-8ed9-3a50986da570"/>
<bqs:last_page>2741</bqs:last_page>
</rdf:Description>
<rdf:Description rdf:about="rdf:#author1Vcard">
<rdf:type rdf:resource="http://www.cellml.org/bqs/1.0#Person"/>
<vCard:N rdf:resource="rdf:#author1VcardN"/>
</rdf:Description>
<rdf:Description rdf:about="rdf:#e26a29bc-0252-485e-aa19-04f621b45f61">
<vCard:Given>Catherine</vCard:Given>
<vCard:Family>Lloyd</vCard:Family>
<vCard:Other>May</vCard:Other>
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Saftenku et al's 2001 markovian model of high activity levels of cardiac ryanodine receptors.
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