- Author:
- pmr2.import <nobody@models.cellml.org>
- Date:
- 2009-06-17 14:11:37+12:00
- Desc:
- committing version01 of fink_slepchenko_loew_1999
- Permanent Source URI:
- https://models.physiomeproject.org/workspace/575/rawfile/6fb93694076209bfeaaebd86d3039c39a17ee052/fink_slepchenko_loew_1999.cellml
<?xml version='1.0' encoding='utf-8'?>
<!-- FILE : fink_model_1999.xml
CREATED : 30th July 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 Fink et al's 1999 model of IP3-mediated Ca2+ release in smooth muscle cells.
CHANGES:
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="fink_slepchenko_loew_1999_version01" name="fink_slepchenko_loew_1999_version01">
<documentation xmlns="http://cellml.org/tmp-documentation">
<article>
<articleinfo>
<title>Intracellular IP3 and Calcium Release in a Smooth Muscle Cell</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>
Intracellular calcium dynamics are frequently the subject of theoretical mathematical models (<ulink url="${HTML_EXMPL_IP3_CA2+_MODEL}">De Young and Keizer, 1992</ulink>, <ulink url="${HTML_EXMPL_LI_MODEL}">Li and Rinzel, 1994</ulink>, <ulink url="${HTML_EXMPL_KEIZER_MODEL}">Keizer and Levine, 1996</ulink>, <ulink url="${HTML_EXMPL_JRW_MODEL}">Jafri-Rice-Winslow, 1998</ulink>, and <ulink url="${HTML_EXMPL_SNYDER_MODEL}">Snyder et al., 2000</ulink> are just a few examples of calcium dynamic models that have been coded up into CellML). The physical and chemical laws of calcium waves and oscillations can be expressed in terms of differential equations describing reaction kinetics, fluxes through membranes, and diffusion.
</para>
<para>
Inositol-1,4,5-triphosphate (IP<subscript>3</subscript>)-mediated calcium release from the endoplasmic reticulum is an important intracellular signalling mechanism in many cell types. In their 1999 study, Fink <emphasis>et al</emphasis>. determine the levels of IP<subscript>3</subscript> required for calcium release in A7r5 cells (a rat smooth muscle cell from the thoracic aorta). Experimental data were used to construct a mathematical model of the IP<subscript>3</subscript>-dependent calcium changes (see <xref linkend="fig_cell_diagram"/> below). This model considers of several elements, including:
<itemizedlist>
<listitem>
<para>the mechanism of the IP<subscript>3</subscript>-receptor;</para>
</listitem>
<listitem>
<para>IP<subscript>3</subscript> degradation;</para>
</listitem>
<listitem>
<para>calcium buffering in the cytosol;</para>
</listitem> and
<listitem>
<para>refilling of the endoplasmic reticulum (ER) calcium stores via sarcoplasmic endoplasmic reticulum ATPase (SERCA) pumps.</para>
</listitem>
</itemizedlist>
</para>
<para>
The calcium response to IP<subscript>3</subscript> release and its subsequent degradation were modelled using <emphasis>Vitual Cell</emphasis> software. By combining experimental and modelling approaches, IP<subscript>3</subscript> and Ca<superscript>2+</superscript> time courses can be directly compared.
</para>
<para>
<ulink url="http://www.biophysj.org/cgi/content/abstract/77/1/617">Determination of Time-Dependent Inositol-1,4,5-Trisphosphate Concentrations during Calcium Release in a Smooth Muscle Cell</ulink>, Charles C. Fink, Boris Slepchenko, and Leslie M. Loew, 1999, <ulink url="http://www.biophysj.org/">
<emphasis>Biophysical Journal</emphasis>
</ulink>, 77, 617-628. (<ulink url="http://www.biophysj.org/cgi/content/full/77/1/617">Full text</ulink> and <ulink url="http://www.biophysj.org/cgi/reprint/77/1/617.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=10388786&dopt=Abstract">PubMed ID: 10388776</ulink>
</para>
<informalfigure float="0" id="fig_cell_diagram">
<mediaobject>
<imageobject>
<objectinfo>
<title>Schematic diagram of model</title>
</objectinfo>
<imagedata fileref="fink_1999.png"/>
</imageobject>
</mediaobject>
</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="micrometre">
<unit units="metre" prefix="micro"/>
</units>
<units name="micromolar_micrometre_per_second">
<unit units="micromolar"/>
<unit units="micrometre"/>
<unit units="second" exponent="-1"/>
</units>
<units name="micrometre_per_second">
<unit units="micrometre"/>
<unit units="second" exponent="-1"/>
</units>
<units name="micrometre_2_per_second">
<unit units="micrometre" exponent="2"/>
<unit units="second" exponent="-1"/>
</units>
<units name="flux">
<unit units="micromolar"/>
<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>
<component name="Calcium_dynamics">
<variable units="micromolar" public_interface="out" name="Ca" initial_value="0.05"/>
<variable units="second" public_interface="in" name="time"/>
<variable units="flux" public_interface="in" name="J_channel"/>
<variable units="flux" public_interface="in" name="J_pump"/>
<variable units="flux" public_interface="in" name="J_leak"/>
<variable units="dimensionless" public_interface="in" name="beta"/>
<math xmlns="http://www.w3.org/1998/Math/MathML">
<apply id="Ca_diff_eq">
<eq/>
<apply>
<diff/>
<bvar>
<ci>time</ci>
</bvar>
<ci> Ca </ci>
</apply>
<apply>
<times/>
<ci> beta </ci>
<apply>
<plus/>
<apply>
<minus/>
<ci> J_channel </ci>
<ci> J_pump </ci>
</apply>
<ci> J_leak </ci>
</apply>
</apply>
</apply>
</math>
</component>
<component name="ER">
<variable units="micromolar" public_interface="out" name="Ca_ER" initial_value="400.0"/>
</component>
<component name="Channel_kinetics">
<variable units="flux" public_interface="out" name="J_channel"/>
<variable units="flux" name="J_max" initial_value="2880.0"/>
<variable units="dimensionless" name="h" initial_value="0.667"/>
<variable units="micromolar" name="K_act" initial_value="0.17"/>
<variable units="micromolar" name="K_I" initial_value="0.03"/>
<variable units="micromolar" name="K_inh" initial_value="0.1"/>
<variable units="second_order_rate_constant" name="k_on" initial_value="8.0"/>
<variable units="micromolar" name="I" initial_value="0.01"/>
<variable units="second" public_interface="in" name="time"/>
<variable units="micromolar" public_interface="in" name="Ca"/>
<variable units="micromolar" public_interface="in" name="Ca_ER"/>
<math xmlns="http://www.w3.org/1998/Math/MathML">
<apply id="J_channel_calculation">
<eq/>
<ci> J_channel </ci>
<apply>
<times/>
<ci> J_max </ci>
<apply>
<power/>
<apply>
<times/>
<apply>
<divide/>
<ci> I </ci>
<apply>
<plus/>
<ci> I </ci>
<ci> K_I </ci>
</apply>
</apply>
<apply>
<divide/>
<ci> Ca </ci>
<apply>
<plus/>
<ci> Ca </ci>
<ci> K_act </ci>
</apply>
</apply>
<ci> h </ci>
</apply>
<cn cellml:units="dimensionless"> 3.0 </cn>
</apply>
<apply>
<minus/>
<cn cellml:units="dimensionless"> 1.0 </cn>
<apply>
<divide/>
<ci> Ca </ci>
<ci> Ca_ER </ci>
</apply>
</apply>
</apply>
</apply>
<apply id="h_diff_eq">
<eq/>
<apply>
<diff/>
<bvar>
<ci> time </ci>
</bvar>
<ci> h </ci>
</apply>
<apply>
<times/>
<ci> k_on </ci>
<apply>
<minus/>
<ci> K_inh </ci>
<apply>
<times/>
<ci> h </ci>
<apply>
<plus/>
<ci> Ca </ci>
<ci> K_inh </ci>
</apply>
</apply>
</apply>
</apply>
</apply>
</math>
</component>
<component name="SERCA_pump_kinetics">
<variable units="flux" public_interface="out" name="J_pump"/>
<variable units="flux" name="V_max" initial_value="5.85"/>
<variable units="micromolar" name="K_p" initial_value="0.24"/>
<variable units="second" public_interface="in" name="time"/>
<variable units="micromolar" public_interface="in" name="Ca"/>
<math xmlns="http://www.w3.org/1998/Math/MathML">
<apply id="J_pump_calculation">
<eq/>
<ci> J_pump </ci>
<apply>
<times/>
<ci> V_max </ci>
<apply>
<divide/>
<apply>
<power/>
<ci> Ca </ci>
<cn cellml:units="dimensionless"> 2.0 </cn>
</apply>
<apply>
<plus/>
<apply>
<power/>
<ci> Ca </ci>
<cn cellml:units="dimensionless"> 2.0 </cn>
</apply>
<apply>
<power/>
<ci> K_p </ci>
<cn cellml:units="dimensionless"> 2.0 </cn>
</apply>
</apply>
</apply>
</apply>
</apply>
</math>
</component>
<component name="Calcium_buffering">
<variable units="dimensionless" public_interface="out" name="beta"/>
<variable units="micromolar" name="B_end" initial_value="12.0"/>
<variable units="micromolar" name="B_ex" initial_value="11.35"/>
<variable units="micromolar" name="K_end" initial_value="0.3"/>
<variable units="micromolar" name="K_ex" initial_value="0.26"/>
<variable units="micromolar" name="Ca_ex"/>
<variable units="second" public_interface="in" name="time"/>
<math xmlns="http://www.w3.org/1998/Math/MathML">
<apply id="beta_calculation">
<eq/>
<ci> beta </ci>
<apply>
<power/>
<apply>
<plus/>
<cn cellml:units="dimensionless"> 1.0 </cn>
<apply>
<divide/>
<ci> B_end </ci>
<ci> K_end </ci>
</apply>
<apply>
<divide/>
<apply>
<times/>
<ci> B_ex </ci>
<ci> K_ex </ci>
</apply>
<apply>
<power/>
<apply>
<plus/>
<ci> Ca_ex </ci>
<ci> K_ex </ci>
</apply>
<cn cellml:units="dimensionless"> 2.0 </cn>
</apply>
</apply>
</apply>
<cn cellml:units="dimensionless"> -1.0 </cn>
</apply>
</apply>
</math>
</component>
<component name="Leak">
<variable units="flux" public_interface="out" name="J_leak"/>
<variable units="flux" name="L" initial_value="0.0804"/>
<variable units="second" public_interface="in" name="time"/>
<variable units="micromolar" public_interface="in" name="Ca"/>
<variable units="micromolar" public_interface="in" name="Ca_ER"/>
<math xmlns="http://www.w3.org/1998/Math/MathML">
<apply id="J_leak_calculation">
<eq/>
<ci> J_leak </ci>
<apply>
<times/>
<ci> L </ci>
<apply>
<minus/>
<cn cellml:units="dimensionless"> 1.0 </cn>
<apply>
<divide/>
<ci> Ca </ci>
<ci> Ca_ER </ci>
</apply>
</apply>
</apply>
</apply>
</math>
</component>
<connection>
<map_components component_2="environment" component_1="Calcium_dynamics"/>
<map_variables variable_2="time" variable_1="time"/>
</connection>
<connection>
<map_components component_2="environment" component_1="Channel_kinetics"/>
<map_variables variable_2="time" variable_1="time"/>
</connection>
<connection>
<map_components component_2="environment" component_1="SERCA_pump_kinetics"/>
<map_variables variable_2="time" variable_1="time"/>
</connection>
<connection>
<map_components component_2="environment" component_1="Leak"/>
<map_variables variable_2="time" variable_1="time"/>
</connection>
<connection>
<map_components component_2="environment" component_1="Calcium_buffering"/>
<map_variables variable_2="time" variable_1="time"/>
</connection>
<connection>
<map_components component_2="Channel_kinetics" component_1="Calcium_dynamics"/>
<map_variables variable_2="Ca" variable_1="Ca"/>
<map_variables variable_2="J_channel" variable_1="J_channel"/>
</connection>
<connection>
<map_components component_2="SERCA_pump_kinetics" component_1="Calcium_dynamics"/>
<map_variables variable_2="Ca" variable_1="Ca"/>
<map_variables variable_2="J_pump" variable_1="J_pump"/>
</connection>
<connection>
<map_components component_2="Leak" component_1="Calcium_dynamics"/>
<map_variables variable_2="Ca" variable_1="Ca"/>
<map_variables variable_2="J_leak" variable_1="J_leak"/>
</connection>
<connection>
<map_components component_2="Calcium_buffering" component_1="Calcium_dynamics"/>
<map_variables variable_2="beta" variable_1="beta"/>
</connection>
<connection>
<map_components component_2="Channel_kinetics" component_1="ER"/>
<map_variables variable_2="Ca_ER" variable_1="Ca_ER"/>
</connection>
<connection>
<map_components component_2="Leak" component_1="ER"/>
<map_variables variable_2="Ca_ER" variable_1="Ca_ER"/>
</connection>
<rdf:RDF>
<rdf:Bag rdf:about="rdf:#1a649420-1110-44ca-88dd-b90da508b157">
<rdf:li>calcium dynamics</rdf:li>
<rdf:li>ip3</rdf:li>
<rdf:li>Smooth Muscle</rdf:li>
<rdf:li>smooth muscle</rdf:li>
<rdf:li>IP3</rdf:li>
</rdf:Bag>
<rdf:Seq rdf:about="rdf:#2074521b-b7d5-4f98-bc52-8bef0bb50e5f">
<rdf:li rdf:resource="rdf:#ab68eaa0-136a-4adf-a07d-7f5da56a2b01"/>
<rdf:li rdf:resource="rdf:#0caa631e-ee04-4421-b26d-47b1e89e68b3"/>
<rdf:li rdf:resource="rdf:#073284f6-b78b-402d-92db-e0caa8b0ec17"/>
</rdf:Seq>
<rdf:Description rdf:about="rdf:#5ee311c6-7337-4632-add4-667c1fee6374">
<dcterms:W3CDTF>2003-04-09</dcterms:W3CDTF>
</rdf:Description>
<rdf:Description rdf:about="rdf:#b24ff8f9-beed-49c0-9a0f-2da36ba2d4d3">
<vCard:Orgname>The University of Auckland</vCard:Orgname>
<vCard:Orgunit>The Bioengineering Institute</vCard:Orgunit>
</rdf:Description>
<rdf:Description rdf:about="rdf:#ab2482eb-f94d-47a5-ae1e-f9ab660ae609">
<dc:subject rdf:resource="rdf:#31314fdf-ac65-4c97-a7c5-d073f7af3c40"/>
</rdf:Description>
<rdf:Description rdf:about="rdf:#e081153c-787d-44d6-b060-37c4150476a8">
<dcterms:W3CDTF>2002-07-30</dcterms:W3CDTF>
</rdf:Description>
<rdf:Description rdf:about="rdf:#31314fdf-ac65-4c97-a7c5-d073f7af3c40">
<bqs:subject_type>keyword</bqs:subject_type>
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</rdf:Description>
<rdf:Description rdf:about="rdf:#8734f611-1680-4e8c-a3de-be92a1202ce7">
<vCard:Given>Autumn</vCard:Given>
<vCard:Family>Cuellar</vCard:Family>
<vCard:Other>A</vCard:Other>
</rdf:Description>
<rdf:Description rdf:about="rdf:#c3cb2460-8666-4f46-a733-03f91bd2e61f">
<dcterms:modified rdf:resource="rdf:#5ee311c6-7337-4632-add4-667c1fee6374"/>
<rdf:value>
Added publication date information.
</rdf:value>
<cmeta:modifier rdf:resource="rdf:#829ea927-976f-4e4c-b050-e068209a9c57"/>
</rdf:Description>
<rdf:Description rdf:about="#fink_slepchenko_loew_1999_version01">
<dc:title>
Fink et al's 1999 model of IP3-mediated Ca2+-release in smooth muscle
cells.
</dc:title>
<cmeta:bio_entity>Smooth Muscle Cell</cmeta:bio_entity>
<cmeta:comment rdf:resource="rdf:#e7f1779b-5eed-4bf9-b981-76a0242c12f6"/>
<bqs:reference rdf:resource="rdf:#6fa23ed4-01b1-491c-8b24-9f30e32bc9c8"/>
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<dc:creator rdf:resource="rdf:#2074521b-b7d5-4f98-bc52-8bef0bb50e5f"/>
<dc:title>
Determination of time-dependent inositol-1,4,5-triphosphate
concentrations during calcium release in a smooth muscle cell
</dc:title>
<bqs:volume>77</bqs:volume>
<bqs:first_page>617</bqs:first_page>
<bqs:Journal rdf:resource="rdf:#8684e6b4-1db7-462d-921a-3918e3240526"/>
<dcterms:issued rdf:resource="rdf:#d2fda1ca-207e-4bb2-8497-eb780ebe72d8"/>
<bqs:last_page>628</bqs:last_page>
</rdf:Description>
<rdf:Description rdf:about="rdf:#21b3948c-15af-4532-beb8-db3880949cc0">
<vCard:Given>Boris</vCard:Given>
<vCard:Family>Slepchenko</vCard:Family>
</rdf:Description>
<rdf:Description rdf:about="rdf:#8684e6b4-1db7-462d-921a-3918e3240526">
<dc:title>Biophysical Journal</dc:title>
</rdf:Description>
<rdf:Description rdf:about="rdf:#d2fda1ca-207e-4bb2-8497-eb780ebe72d8">
<dcterms:W3CDTF>1999-07</dcterms:W3CDTF>
</rdf:Description>
<rdf:Description rdf:about="rdf:#6f62ffbf-434d-47f8-85cd-0abbb8ae43e1">
<vCard:FN>Catherine Lloyd</vCard:FN>
</rdf:Description>
<rdf:Description rdf:about="rdf:#0caa631e-ee04-4421-b26d-47b1e89e68b3">
<rdf:type rdf:resource="http://www.cellml.org/bqs/1.0#Person"/>
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<rdf:Description rdf:about="rdf:#6fa23ed4-01b1-491c-8b24-9f30e32bc9c8">
<bqs:Pubmed_id>10388786</bqs:Pubmed_id>
<bqs:JournalArticle rdf:resource="rdf:#8d707487-9190-47ba-b229-dc3742b211a8"/>
</rdf:Description>
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<dc:creator rdf:resource="rdf:#6f62ffbf-434d-47f8-85cd-0abbb8ae43e1"/>
<rdf:value>
This is the CellML description of Fink et al's 1999 model of
IP3-mediated Ca2+ release in smooth muscle cells.
</rdf:value>
</rdf:Description>
<rdf:Description rdf:about="rdf:#c6645d90-993d-4dbc-a5e2-2b393762b021">
<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="">
<dc:publisher>
The University of Auckland, Bioengineering Institute
</dc:publisher>
<cmeta:modification rdf:resource="rdf:#c3cb2460-8666-4f46-a733-03f91bd2e61f"/>
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<dc:creator rdf:resource="rdf:#8360736d-fbb5-4b76-b5da-f2e6fae1cab6"/>
</rdf:Description>
<rdf:Description rdf:about="rdf:#70db4dcb-52f5-448d-a02b-a46a851b5f46">
<vCard:Given>Catherine</vCard:Given>
<vCard:Family>Lloyd</vCard:Family>
<vCard:Other>May</vCard:Other>
</rdf:Description>
<rdf:Description rdf:about="rdf:#0f394e85-02a2-43bd-be73-9f282cc2a021">
<vCard:Given>Charles</vCard:Given>
<vCard:Family>Fink</vCard:Family>
<vCard:Other>C</vCard:Other>
</rdf:Description>
<rdf:Description rdf:about="rdf:#829ea927-976f-4e4c-b050-e068209a9c57">
<vCard:N rdf:resource="rdf:#8734f611-1680-4e8c-a3de-be92a1202ce7"/>
</rdf:Description>
<rdf:Description rdf:about="rdf:#18690245-a8d3-4422-acfe-c87402f435c6">
<vCard:Given>Leslie</vCard:Given>
<vCard:Family>Loew</vCard:Family>
<vCard:Other>M</vCard:Other>
</rdf:Description>
</rdf:RDF>
</model>
