<?xml version="1.0"?>
<!--
This CellML file was generated on 13/05/2010 at 3:13:21 at p.m. using:
COR (0.9.31.1371)
Copyright 2002-2010 Dr Alan Garny
http://cor.physiol.ox.ac.uk/ - cor@physiol.ox.ac.uk
CellML 1.0 was used to generate this model
http://www.cellml.org/
--><model xmlns="http://www.cellml.org/cellml/1.0#" xmlns:cmeta="http://www.cellml.org/metadata/1.0#" cmeta:id="sneyd_2002" name="sneyd_2002">
<documentation xmlns="http://cellml.org/tmp-documentation">
<article>
<articleinfo>
<title>A Dynamic Model Of The Type-2 Inositol Triphosphate Receptor</title>
<author>
<firstname>Catherine</firstname>
<surname>Lloyd</surname>
<affiliation>
<shortaffil>Auckland Bioengineering Institute, The University of Auckland</shortaffil>
</affiliation>
</author>
</articleinfo>
<section id="sec_status">
<title>Model Status</title>
<para>
This CellML model runs in OpenCell and COR and the units are consistent throughout. The model runs to recreate published results and is currently configured to recreate Figure 4 (Lower Plot, Trace 4), but variation of the IP3 and Calcium concentrations will allow the model to recreate different figures.
</para>
</section>
<sect1 id="sec_structure">
<title>Model Structure</title>
<para>
ABSTRACT: The dynamic properties of the inositol (1,4,5)-trisphosphate (IP(3)) receptor are crucial for the control of intracellular Ca(2+), including the generation of Ca(2+) oscillations and waves. However, many models of this receptor do not agree with recent experimental data on the dynamic responses of the receptor. We construct a model of the IP(3) receptor and fit the model to dynamic and steady-state experimental data from type-2 IP(3) receptors. Our results indicate that, (i) Ca(2+) binds to the receptor using saturating, not mass-action, kinetics; (ii) Ca(2+) decreases the rate of IP(3) binding while simultaneously increasing the steady-state sensitivity of the receptor to IP(3); (iii) the rate of Ca(2+)-induced receptor activation increases with Ca(2+) and is faster than Ca(2+)-induced receptor inactivation; and (iv) IP(3) receptors are sequentially activated and inactivated by Ca(2+) even when IP(3) is bound. Our results emphasize that measurement of steady-state properties alone is insufficient to characterize the functional properties of the receptor.
</para>
<para>
The original paper reference is cited below:
</para>
<para>
A dynamic model of the type-2 inositol triphosphate receptor, James Sneyd and Jean-Francois Dufour, 2002, <emphasis>Proceedings of the National Academy of Sciences </emphasis>, 99, 2398-2403. <ulink url="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=11842185&dopt=Abstract">PubMed ID: 11842185</ulink>
</para>
<informalfigure float="0" id="fig_simplified_diagram">
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<title>A simplified diagram of the IPR model</title>
</objectinfo>
<imagedata fileref="sneyd_2002.png"/>
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<caption>A simplified diagram of the IPR model, where R represents the free receptor, O is the open state of the channel, A is the activated state of the channel and I1, I2, and S are three inactive states.</caption>
</informalfigure>
</sect1>
</article>
</documentation>
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<rdf:RDF xmlns:rdf="http://www.w3.org/1999/02/22-rdf-syntax-ns#"><rdf:Description rdf:about="rdf:#9495dff1-73e0-413c-aadf-7967fca1ffb7"><creator xmlns="http://purl.org/dc/elements/1.1/"><rdf:Description rdf:about="rdf:#6111cd36-0957-42ed-a020-0a413b58e32e"/></creator><title xmlns="http://purl.org/dc/elements/1.1/" xml:lang="en">A dynamic model of the type-2 inositol triphosphate receptor</title><volume xmlns="http://www.cellml.org/bqs/1.0#" xml:lang="en">99</volume><Journal xmlns="http://www.cellml.org/bqs/1.0#"><rdf:Description rdf:about="rdf:#cef5a763-b1c9-4c6b-8bc9-9daaa5b9e08a"/></Journal><last_page xmlns="http://www.cellml.org/bqs/1.0#" xml:lang="en">2403</last_page><issued xmlns="http://purl.org/dc/terms/"><rdf:Description rdf:about="rdf:#cd8712b1-d799-48cd-b7ca-42ef82b1ed24"/></issued><first_page xmlns="http://www.cellml.org/bqs/1.0#" xml:lang="en">2398</first_page></rdf:Description><rdf:Description rdf:about="rdf:#9249daff-b2ed-4a5a-aa13-f3384eb279ff"><subject xmlns="http://purl.org/dc/elements/1.1/"><rdf:Description rdf:about="rdf:#8de13f80-a3fe-45a0-820f-328debc8faa1"/></subject></rdf:Description><rdf:Description rdf:about="rdf:#292f31fd-3a27-479c-994d-5e112c60017a"><rdf:type><rdf:Description rdf:about="http://www.cellml.org/bqs/1.0#Person"/></rdf:type><N xmlns="http://www.w3.org/2001/vcard-rdf/3.0#"><rdf:Description rdf:about="rdf:#831499e1-8b9d-4194-a720-c3b8c89d806c"/></N></rdf:Description><rdf:Description rdf:about="rdf:#f2f72219-83b7-4a26-bcc9-29a1701dd667"><W3CDTF xmlns="http://purl.org/dc/terms/" xml:lang="en">2007-06-05T10:45:11+12:00</W3CDTF></rdf:Description><rdf:Description rdf:about="rdf:#26734d27-c924-44b8-aa7f-f2a76a180491"><Given xmlns="http://www.w3.org/2001/vcard-rdf/3.0#" xml:lang="en">Jean-Francois</Given><Family xmlns="http://www.w3.org/2001/vcard-rdf/3.0#" xml:lang="en">Dufour</Family></rdf:Description><rdf:Description rdf:about="rdf:#0585328f-cbc9-4041-96cb-f7a0033edd46"><creator xmlns="http://purl.org/dc/elements/1.1/"><rdf:Description rdf:about="rdf:#2aa54fd4-e809-41fd-bda4-e52b56340014"/></creator></rdf:Description><rdf:Description rdf:about="rdf:#8de13f80-a3fe-45a0-820f-328debc8faa1"><subject_type xmlns="http://www.cellml.org/bqs/1.0#" xml:lang="en">keyword</subject_type><rdf:value><rdf:Description rdf:about="rdf:#b865b3df-b00a-4e44-a8ce-886187f7eea9"/></rdf:value></rdf:Description><rdf:Description rdf:nodeID="n1"><endingValue xmlns="http://www.cellml.org/metadata/simulation/1.0#" xml:lang="en">1.5</endingValue><pointDensity xmlns="http://www.cellml.org/metadata/simulation/1.0#nonstandard-" xml:lang="en">10000</pointDensity><maximumStepSize xmlns="http://www.cellml.org/metadata/simulation/1.0#" xml:lang="en">0.1</maximumStepSize></rdf:Description><rdf:Description rdf:about="rdf:#600a325c-8a8b-43ac-b8d7-625a5b7d799b"><rdf:type><rdf:Description rdf:about="http://www.cellml.org/bqs/1.0#Person"/></rdf:type><N xmlns="http://www.w3.org/2001/vcard-rdf/3.0#"><rdf:Description rdf:about="rdf:#26734d27-c924-44b8-aa7f-f2a76a180491"/></N></rdf:Description><rdf:Description rdf:about="rdf:#1e5ab40f-1204-4fb3-b0d3-e4eacac36090"><FN xmlns="http://www.w3.org/2001/vcard-rdf/3.0#" xml:lang="en">Catherine Lloyd</FN></rdf:Description><rdf:Description rdf:about="rdf:#29bca02a-d2e6-42a9-a72d-ee3bd1c02895"><rdf:value xml:lang="en">Corrected two of the equations.</rdf:value><cmeta:modifier><rdf:Description rdf:about="rdf:#078e99d0-2315-42a3-bf2b-b1698d1bb949"/></cmeta:modifier><modified xmlns="http://purl.org/dc/terms/"><rdf:Description rdf:about="rdf:#2b0b970c-3794-4508-8999-7edbf7adeb0e"/></modified></rdf:Description><rdf:Description rdf:about="rdf:#f9b5f6cb-de92-4bdd-829c-b9ef7252d9c8"><Given xmlns="http://www.w3.org/2001/vcard-rdf/3.0#" xml:lang="en">Catherine</Given><Family xmlns="http://www.w3.org/2001/vcard-rdf/3.0#" xml:lang="en">Lloyd</Family><Other xmlns="http://www.w3.org/2001/vcard-rdf/3.0#" xml:lang="en">May</Other></rdf:Description><rdf:Description rdf:about="rdf:#c339100b-a635-424f-bcba-ce571d03dbab"><JournalArticle xmlns="http://www.cellml.org/bqs/1.0#"><rdf:Description rdf:about="rdf:#9495dff1-73e0-413c-aadf-7967fca1ffb7"/></JournalArticle><Pubmed_id xmlns="http://www.cellml.org/bqs/1.0#" xml:lang="en">11842185</Pubmed_id></rdf:Description><rdf:Description rdf:about="#O"><title xmlns="http://purl.org/dc/elements/1.1/" xml:lang="en">O</title><alternative xmlns="http://purl.org/dc/terms/" xml:lang="en">Open state</alternative></rdf:Description><rdf:Description rdf:about=""><creator xmlns="http://purl.org/dc/elements/1.1/"><rdf:Description rdf:about="rdf:#d222b477-b54b-48d5-842e-ae09a9a11530"/></creator><cmeta:comment><rdf:Description rdf:about="rdf:#0585328f-cbc9-4041-96cb-f7a0033edd46"/></cmeta:comment><cmeta:modification><rdf:Description rdf:about="rdf:#34ba7e21-a71a-42c1-b9f8-b5f4cdf10238"/></cmeta:modification><cmeta:modification><rdf:Description rdf:about="rdf:#29bca02a-d2e6-42a9-a72d-ee3bd1c02895"/></cmeta:modification><publisher xmlns="http://purl.org/dc/elements/1.1/" xml:lang="en">The University of Auckland, Auckland Bioengineering Institute</publisher><created xmlns="http://purl.org/dc/terms/"><rdf:Description rdf:about="rdf:#2b47520f-a27e-4206-8b9d-38f2685816a1"/></created></rdf:Description><rdf:Description rdf:about="#I_2"><title xmlns="http://purl.org/dc/elements/1.1/" xml:lang="en">I_1</title><alternative xmlns="http://purl.org/dc/terms/" xml:lang="en">Inactive state 2</alternative></rdf:Description><rdf:Description rdf:about="rdf:#06465ad8-e922-4b22-8d2e-a63d6de45d0c"><rdf:value xml:lang="en">This is the CellML description of Sneyd and Dufour's 2002 dynamic model of type-2 inositol triphosphate receptor. The dynamic properties of this receptor are essential for the control of intracellular calcium, including the generation of calcium oscillations and waves.</rdf:value><creator xmlns="http://purl.org/dc/elements/1.1/"><rdf:Description rdf:about="rdf:#1e5ab40f-1204-4fb3-b0d3-e4eacac36090"/></creator></rdf:Description><rdf:Description rdf:about="rdf:#2b0b970c-3794-4508-8999-7edbf7adeb0e"><W3CDTF xmlns="http://purl.org/dc/terms/" xml:lang="en">2007-05-24T08:10:03+12:00</W3CDTF></rdf:Description><rdf:Description rdf:nodeID="n2"><rdf:rest><rdf:Description rdf:about="http://www.w3.org/1999/02/22-rdf-syntax-ns#nil"/></rdf:rest><rdf:first><rdf:Description rdf:nodeID="n1"/></rdf:first></rdf:Description><rdf:Description rdf:nodeID="n3"><boundIntervals xmlns="http://www.cellml.org/metadata/simulation/1.0#"><rdf:Description rdf:nodeID="n2"/></boundIntervals></rdf:Description><rdf:Description rdf:about="rdf:#c581990a-df08-484b-8f3d-de84e02c2b7a"><N xmlns="http://www.w3.org/2001/vcard-rdf/3.0#"><rdf:Description rdf:about="rdf:#f9b5f6cb-de92-4bdd-829c-b9ef7252d9c8"/></N></rdf:Description><rdf:Description rdf:about="rdf:#b865b3df-b00a-4e44-a8ce-886187f7eea9"><rdf:type><rdf:Description rdf:about="http://www.w3.org/1999/02/22-rdf-syntax-ns#Bag"/></rdf:type><rdf:_1 xml:lang="en">calcium dynamics</rdf:_1><rdf:_2 xml:lang="en">IP3 receptor</rdf:_2></rdf:Description><rdf:Description rdf:about="rdf:#2b47520f-a27e-4206-8b9d-38f2685816a1"><W3CDTF xmlns="http://purl.org/dc/terms/" xml:lang="en">2007-05-22T00:00:00+00:00</W3CDTF></rdf:Description><rdf:Description rdf:about="rdf:#d222b477-b54b-48d5-842e-ae09a9a11530"><N xmlns="http://www.w3.org/2001/vcard-rdf/3.0#"><rdf:Description rdf:about="rdf:#67d268c3-19f0-420c-9721-31f6f32f6324"/></N><EMAIL xmlns="http://www.w3.org/2001/vcard-rdf/3.0#"><rdf:Description rdf:about="rdf:#a8ab691f-d35c-49a9-b512-886d9896095b"/></EMAIL><ORG xmlns="http://www.w3.org/2001/vcard-rdf/3.0#"><rdf:Description rdf:about="rdf:#35ad1886-9cab-44b7-8756-237b235f3ae8"/></ORG></rdf:Description><rdf:Description rdf:about="#A"><title xmlns="http://purl.org/dc/elements/1.1/" xml:lang="en">A</title><alternative xmlns="http://purl.org/dc/terms/" xml:lang="en">Active state</alternative></rdf:Description><rdf:Description rdf:about="rdf:#cef5a763-b1c9-4c6b-8bc9-9daaa5b9e08a"><title xmlns="http://purl.org/dc/elements/1.1/" xml:lang="en">PNAS</title></rdf:Description><rdf:Description rdf:about="rdf:#35ad1886-9cab-44b7-8756-237b235f3ae8"><Orgunit xmlns="http://www.w3.org/2001/vcard-rdf/3.0#" xml:lang="en">Auckland Bioengineering Institute</Orgunit><Orgname xmlns="http://www.w3.org/2001/vcard-rdf/3.0#" xml:lang="en">The University of Auckland</Orgname></rdf:Description><rdf:Description rdf:about="rdf:#cd8712b1-d799-48cd-b7ca-42ef82b1ed24"><W3CDTF xmlns="http://purl.org/dc/terms/" xml:lang="en">2002-02-19</W3CDTF></rdf:Description><rdf:Description rdf:about="rdf:#31ab70d4-dd42-4248-badc-de88f84942c2"><Given xmlns="http://www.w3.org/2001/vcard-rdf/3.0#" xml:lang="en">Catherine</Given><Family xmlns="http://www.w3.org/2001/vcard-rdf/3.0#" xml:lang="en">Lloyd</Family><Other xmlns="http://www.w3.org/2001/vcard-rdf/3.0#" xml:lang="en">May</Other></rdf:Description><rdf:Description rdf:about="rdf:#831499e1-8b9d-4194-a720-c3b8c89d806c"><Given xmlns="http://www.w3.org/2001/vcard-rdf/3.0#" xml:lang="en">James</Given><Family xmlns="http://www.w3.org/2001/vcard-rdf/3.0#" xml:lang="en">Sneyd</Family></rdf:Description><rdf:Description rdf:about="rdf:#67d268c3-19f0-420c-9721-31f6f32f6324"><Given xmlns="http://www.w3.org/2001/vcard-rdf/3.0#" xml:lang="en">Catherine</Given><Family xmlns="http://www.w3.org/2001/vcard-rdf/3.0#" xml:lang="en">Lloyd</Family><Other xmlns="http://www.w3.org/2001/vcard-rdf/3.0#" xml:lang="en">May</Other></rdf:Description><rdf:Description rdf:about="#R"><title xmlns="http://purl.org/dc/elements/1.1/" xml:lang="en">R</title><alternative xmlns="http://purl.org/dc/terms/" xml:lang="en">Receptor</alternative></rdf:Description><rdf:Description rdf:about="#I_1"><title xmlns="http://purl.org/dc/elements/1.1/" xml:lang="en">I_1</title><alternative xmlns="http://purl.org/dc/terms/" xml:lang="en">Inactive state 1</alternative></rdf:Description><rdf:Description rdf:about="rdf:#34ba7e21-a71a-42c1-b9f8-b5f4cdf10238"><rdf:value xml:lang="en">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 and gives a nice curved output.</rdf:value><cmeta:modifier><rdf:Description rdf:about="rdf:#c581990a-df08-484b-8f3d-de84e02c2b7a"/></cmeta:modifier><modified xmlns="http://purl.org/dc/terms/"><rdf:Description rdf:about="rdf:#f2f72219-83b7-4a26-bcc9-29a1701dd667"/></modified></rdf:Description><rdf:Description rdf:about="rdf:#6111cd36-0957-42ed-a020-0a413b58e32e"><rdf:type><rdf:Description rdf:about="http://www.w3.org/1999/02/22-rdf-syntax-ns#Seq"/></rdf:type><rdf:_1><rdf:Description rdf:about="rdf:#292f31fd-3a27-479c-994d-5e112c60017a"/></rdf:_1><rdf:_2><rdf:Description rdf:about="rdf:#600a325c-8a8b-43ac-b8d7-625a5b7d799b"/></rdf:_2></rdf:Description><rdf:Description rdf:about="rdf:#a8ab691f-d35c-49a9-b512-886d9896095b"><rdf:type><rdf:Description rdf:about="http://imc.org/vCard/3.0#internet"/></rdf:type><rdf:value xml:lang="en">c.lloyd@auckland.ac.nz</rdf:value></rdf:Description><rdf:Description rdf:about="#sneyd_2002"><cmeta:comment><rdf:Description rdf:about="rdf:#06465ad8-e922-4b22-8d2e-a63d6de45d0c"/></cmeta:comment><title xmlns="http://purl.org/dc/elements/1.1/" xml:lang="en">
The Sneyd-Dufour 2002 dynamic model of the type-2 inositol triphosphate receptor.
</title><reference xmlns="http://www.cellml.org/bqs/1.0#"><rdf:Description rdf:about="rdf:#9249daff-b2ed-4a5a-aa13-f3384eb279ff"/></reference><reference xmlns="http://www.cellml.org/bqs/1.0#"><rdf:Description rdf:about="rdf:#c339100b-a635-424f-bcba-ce571d03dbab"/></reference><simulation xmlns="http://www.cellml.org/metadata/simulation/1.0#"><rdf:Description rdf:nodeID="n3"/></simulation></rdf:Description><rdf:Description rdf:about="rdf:#078e99d0-2315-42a3-bf2b-b1698d1bb949"><N xmlns="http://www.w3.org/2001/vcard-rdf/3.0#"><rdf:Description rdf:about="rdf:#31ab70d4-dd42-4248-badc-de88f84942c2"/></N></rdf:Description><rdf:Description rdf:about="#S"><title xmlns="http://purl.org/dc/elements/1.1/" xml:lang="en">S</title><alternative xmlns="http://purl.org/dc/terms/" xml:lang="en">Shut state</alternative></rdf:Description></rdf:RDF></model>
