<?xml version='1.0' encoding='utf-8'?>
<!-- FILE : colegrove_model_2000.xml
CREATED : 21st 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 Colegrove et al's
2000 model of mitochondrial Ca2+ uptake and release pathways in sympathetic neurons.
CHANGES:
18/07/2002 - CML - Added more metadata.
28/03/2003 - AAC - Changed the name and cmeta:id of the model to reflect the
proper spelling of Colegrove.
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="colegrove_albrecht_friel_2000_version01" name="colegrove_albrecht_friel_2000_version01">
<documentation xmlns="http://cellml.org/tmp-documentation">
<article>
<articleinfo>
<title>Quantitative Analysis Of Mitochondrial Ca2+ Uptake And Release Pathways In Sympathetic Neurons</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 can not be solved as it is unsuitably constrained.
</para>
<para>
ValidateCellML verifies this model as valid CellML with consistent units.
</para>
</section>
<sect1 id="sec_structure">
<title>Model Structure</title>
<para>
One of the central goals in the study of calcium signalling is to understand the basis of [Ca<superscript>2+</superscript>] dynamics. This is complicated by the fact that Ca<superscript>2+</superscript> is present in several membrane-bound intracellular compartments, each of which uses a distinct Ca<superscript>2+</superscript> transport system and the rate of Ca<superscript>2+</superscript> transport between these compartments can exhibit a complex non-linear dependence on free [Ca<superscript>2+</superscript>].
</para>
<para>
In their 2000 model, Stephen L. Colegrove, Meredith A. Albrecht and David D. Friel have studied how mitochondrial Ca<superscript>2+</superscript> transport contributes to the redistribution of intracellular Ca<superscript>2+</superscript> during and after depolarisation-evoked Ca<superscript>2+</superscript> entry in sympathetic neurons. The total Ca<superscript>2+</superscript> flux during the recovery phase following membrane depolarisation was divided into three components (see <xref linkend="fig_cell_diagram"/> below): one representing net Ca<superscript>2+</superscript> extrusion across the plasma membrane (J<subscript>extru</subscript>), one representing mitochondrial Ca<superscript>2+</superscript> uptake via the uniporter (J<subscript>uni</subscript>) and one representing mitochondrial Ca<superscript>2+</superscript> release via the Na<superscript>+</superscript>/Ca<superscript>2+</superscript> exchanger (J<subscript>NaCa</subscript>). This mathematical model has been translated into a CellML description which can be downloaded in various formats as described in <xref linkend="sec_download_this_model"/>.
</para>
<para>
The complete original paper reference is cited below:
</para>
<para>
Quantitative Analysis of Mitochondrial Ca<superscript>2+</superscript> Uptake and Release Pathways in Sympathetic Neurons <emphasis>Reconstruction of the Recovery after Depolarisation-evoked [Ca<superscript>2+</superscript>] Elevations</emphasis>
, Stephen L. Colegrove, Meredith A. Albrecht and David D. Friel, 2000,
<emphasis>The Journal Of General Physiology</emphasis>
, 115, 371-388. <ulink url="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=10694264&dopt=Abstract">PubMed ID: 10694264</ulink>
</para>
<informalfigure float="0" id="fig_cell_diagram">
<mediaobject>
<imageobject>
<objectinfo>
<title>cell schematic for the model</title>
</objectinfo>
<imagedata fileref="colegrove_2000.png"/>
</imageobject>
</mediaobject>
<caption>Schematic of the model indicating Ca<superscript>2+</superscript> compartmentalization in the extracellular matrix, cytosol and the mitochondrial matrix and pathways for Ca<superscript>2+</superscript> ion movement between the compartments.</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="per_second">
<unit units="second" exponent="-1"/>
</units>
<units name="millivolt">
<unit units="volt" prefix="milli"/>
</units>
<units name="micromolar">
<unit units="mole" prefix="micro"/>
<unit units="litre" exponent="-1"/>
</units>
<units name="nanomolar">
<unit units="mole" prefix="nano"/>
<unit units="litre" exponent="-1"/>
</units>
<units name="nanomolar_per_second">
<unit units="nanomolar"/>
<unit units="second" exponent="-1"/>
</units>
<units name="micromolar_per_second">
<unit units="micromolar"/>
<unit units="second" exponent="-1"/>
</units>
<units name="micro_litre">
<unit units="litre" prefix="micro"/>
</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="Ca_extrusion_across_the_plasma_membrane">
<variable units="nanomolar_per_second" public_interface="out" name="J_pm"/>
<variable units="nanomolar_per_second" name="J_leak"/>
<variable units="nanomolar_per_second" name="J_extru"/>
<variable units="per_second" name="k_leak" initial_value="0.00000037"/>
<variable units="nanomolar_per_second" name="Vmax_extru" initial_value="28.3"/>
<variable units="nanomolar" name="EC50_extru" initial_value="378.8"/>
<variable units="dimensionless" name="n_extru" initial_value="1.8"/>
<variable units="nanomolar" name="Ca_o" initial_value="0.002"/>
<variable units="nanomolar" public_interface="in" name="Ca_i"/>
<variable units="second" public_interface="in" name="time"/>
<math xmlns="http://www.w3.org/1998/Math/MathML">
<apply id="J_pm_calculation">
<eq/>
<ci> J_pm </ci>
<apply>
<plus/>
<ci> J_leak </ci>
<ci> J_extru </ci>
</apply>
</apply>
<apply id="J_leak_calculation">
<eq/>
<ci> J_leak </ci>
<apply>
<times/>
<ci> k_leak </ci>
<apply>
<minus/>
<ci> Ca_i </ci>
<ci> Ca_o </ci>
</apply>
</apply>
</apply>
<apply id="J_extru_calculation">
<eq/>
<ci> J_extru </ci>
<apply>
<divide/>
<ci> Vmax_extru </ci>
<apply>
<plus/>
<cn cellml:units="dimensionless"> 1.0 </cn>
<apply>
<power/>
<apply>
<divide/>
<ci> EC50_extru </ci>
<ci> Ca_i </ci>
</apply>
<ci> n_extru </ci>
</apply>
</apply>
</apply>
</apply>
</math>
</component>
<component name="mitochondrial_Ca_uptake">
<variable units="nanomolar_per_second" public_interface="out" name="J_uni"/>
<variable units="per_second" name="kuni_max" initial_value="75.9"/>
<variable units="micromolar" name="EC50_uni" initial_value="10.0"/>
<variable units="dimensionless" name="n_uni" initial_value="2.0"/>
<variable units="nanomolar" public_interface="in" name="Ca_i"/>
<variable units="second" public_interface="in" name="time"/>
<math xmlns="http://www.w3.org/1998/Math/MathML">
<apply id="J_uni_calculation">
<eq/>
<ci> J_uni </ci>
<apply>
<divide/>
<apply>
<times/>
<ci> kuni_max </ci>
<ci> Ca_i </ci>
</apply>
<apply>
<plus/>
<cn cellml:units="dimensionless"> 1.0 </cn>
<apply>
<power/>
<apply>
<divide/>
<ci> EC50_uni </ci>
<ci> Ca_i </ci>
</apply>
<ci> n_uni </ci>
</apply>
</apply>
</apply>
</apply>
</math>
</component>
<component name="mitochondrial_Ca_release">
<variable units="nanomolar_per_second" public_interface="out" name="J_NaCa"/>
<variable units="nanomolar_per_second" public_interface="out" name="Ca_inhibited_J_NaCa"/>
<variable units="nanomolar_per_second" public_interface="out" name="J_mito"/>
<variable units="nanomolar_per_second" name="Vmax_NaCa" initial_value="-35.0"/>
<variable units="nanomolar" name="EC50_NaCa" initial_value="307.0"/>
<variable units="dimensionless" name="n_inhib" initial_value="6.0"/>
<variable units="nanomolar" name="k_inhib" initial_value="500.0"/>
<variable units="dimensionless" name="delta_Ca_i"/>
<variable units="nanomolar_per_second" public_interface="in" name="J_uni"/>
<variable units="nanomolar" public_interface="in" name="Ca_i"/>
<variable units="nanomolar" public_interface="in" name="Ca_m"/>
<variable units="second" public_interface="in" name="time"/>
<math xmlns="http://www.w3.org/1998/Math/MathML">
<apply id="J_NaCa_calculation">
<eq/>
<ci> J_NaCa </ci>
<apply>
<divide/>
<apply>
<minus/>
<ci> Vmax_NaCa </ci>
</apply>
<apply>
<plus/>
<cn cellml:units="dimensionless"> 1.0 </cn>
<apply>
<divide/>
<ci> EC50_NaCa </ci>
<ci> Ca_m </ci>
</apply>
</apply>
</apply>
</apply>
<apply id="Ca_inhibited_J_NaCa_calculation">
<eq/>
<ci> Ca_inhibited_J_NaCa </ci>
<apply>
<divide/>
<apply>
<minus/>
<apply>
<times/>
<ci> delta_Ca_i </ci>
<ci> Vmax_NaCa </ci>
</apply>
</apply>
<apply>
<plus/>
<cn cellml:units="dimensionless"> 1.0 </cn>
<apply>
<divide/>
<ci> EC50_NaCa </ci>
<ci> Ca_i </ci>
</apply>
</apply>
</apply>
</apply>
<apply id="delta_Ca_i_calculation">
<eq/>
<ci> delta_Ca_i </ci>
<apply>
<minus/>
<cn cellml:units="dimensionless"> 1.0 </cn>
<apply>
<divide/>
<cn cellml:units="dimensionless"> 1.0 </cn>
<apply>
<minus/>
<cn cellml:units="dimensionless"> 1.0 </cn>
<apply>
<power/>
<apply>
<divide/>
<ci> k_inhib </ci>
<ci> Ca_i </ci>
</apply>
<ci> n_inhib </ci>
</apply>
</apply>
</apply>
</apply>
</apply>
<apply id="J_mito_calculation">
<eq/>
<ci> J_mito </ci>
<apply>
<plus/>
<ci> J_uni </ci>
<ci> J_NaCa </ci>
</apply>
</apply>
</math>
</component>
<component name="intracellular_calcium">
<variable units="nanomolar" public_interface="out" name="Ca_i"/>
<variable units="nanomolar_per_second" public_interface="in" name="J_pm"/>
<variable units="nanomolar_per_second" public_interface="in" name="J_mito"/>
<variable units="second" public_interface="in" name="time"/>
<math xmlns="http://www.w3.org/1998/Math/MathML">
<apply id="Ca_i_diff_eq">
<eq/>
<apply>
<diff/>
<bvar>
<ci> time </ci>
</bvar>
<ci> Ca_i </ci>
</apply>
<apply>
<minus/>
<apply>
<plus/>
<ci> J_pm </ci>
<ci> J_mito </ci>
</apply>
</apply>
</apply>
</math>
</component>
<component name="mitochondrial_calcium">
<variable units="nanomolar" public_interface="out" name="Ca_m"/>
<variable units="dimensionless" name="gamma" initial_value="2.0"/>
<variable units="micro_litre" name="v_m"/>
<variable units="dimensionless" name="k_m"/>
<variable units="micro_litre" name="v_i"/>
<variable units="dimensionless" name="k_i"/>
<variable units="nanomolar_per_second" public_interface="in" name="J_mito"/>
<variable units="second" public_interface="in" name="time"/>
<math xmlns="http://www.w3.org/1998/Math/MathML">
<apply id="Ca_m_diff_eq">
<eq/>
<apply>
<diff/>
<bvar>
<ci> time </ci>
</bvar>
<ci> Ca_m </ci>
</apply>
<apply>
<divide/>
<ci> J_mito </ci>
<ci> gamma </ci>
</apply>
</apply>
<apply id="gamma_calculation">
<eq/>
<ci> gamma </ci>
<apply>
<divide/>
<apply>
<times/>
<ci> v_m </ci>
<ci> k_m </ci>
</apply>
<apply>
<times/>
<ci> v_i </ci>
<ci> k_i </ci>
</apply>
</apply>
</apply>
</math>
</component>
<connection>
<map_components component_2="environment" component_1="Ca_extrusion_across_the_plasma_membrane"/>
<map_variables variable_2="time" variable_1="time"/>
</connection>
<connection>
<map_components component_2="environment" component_1="mitochondrial_Ca_uptake"/>
<map_variables variable_2="time" variable_1="time"/>
</connection>
<connection>
<map_components component_2="environment" component_1="mitochondrial_Ca_release"/>
<map_variables variable_2="time" variable_1="time"/>
</connection>
<connection>
<map_components component_2="environment" component_1="intracellular_calcium"/>
<map_variables variable_2="time" variable_1="time"/>
</connection>
<connection>
<map_components component_2="environment" component_1="mitochondrial_calcium"/>
<map_variables variable_2="time" variable_1="time"/>
</connection>
<connection>
<map_components component_2="intracellular_calcium" component_1="Ca_extrusion_across_the_plasma_membrane"/>
<map_variables variable_2="J_pm" variable_1="J_pm"/>
<map_variables variable_2="Ca_i" variable_1="Ca_i"/>
</connection>
<connection>
<map_components component_2="intracellular_calcium" component_1="mitochondrial_Ca_uptake"/>
<map_variables variable_2="Ca_i" variable_1="Ca_i"/>
</connection>
<connection>
<map_components component_2="mitochondrial_Ca_release" component_1="mitochondrial_Ca_uptake"/>
<map_variables variable_2="J_uni" variable_1="J_uni"/>
</connection>
<connection>
<map_components component_2="intracellular_calcium" component_1="mitochondrial_Ca_release"/>
<map_variables variable_2="J_mito" variable_1="J_mito"/>
<map_variables variable_2="Ca_i" variable_1="Ca_i"/>
</connection>
<connection>
<map_components component_2="mitochondrial_calcium" component_1="mitochondrial_Ca_release"/>
<map_variables variable_2="Ca_m" variable_1="Ca_m"/>
<map_variables variable_2="J_mito" variable_1="J_mito"/>
</connection>
<rdf:RDF>
<rdf:Bag rdf:about="rdf:#c32af19e-6bc0-4535-b0e3-d355cba81348">
<rdf:li>calcium dynamics</rdf:li>
<rdf:li>neuron</rdf:li>
<rdf:li>sympathetic</rdf:li>
<rdf:li>electrophysiology</rdf:li>
</rdf:Bag>
<rdf:Seq rdf:about="rdf:#66e8815f-2d77-46f0-b46a-a2919d8eaa70">
<rdf:li rdf:resource="rdf:#9f11eca5-e8ee-463d-a892-860bf0299d1d"/>
<rdf:li rdf:resource="rdf:#54804b41-fa52-4e5d-8d24-bf840a9363ad"/>
<rdf:li rdf:resource="rdf:#4c55cf6c-5bc2-4dfb-9333-cdcb363bdb54"/>
</rdf:Seq>
<rdf:Description rdf:about="">
<dc:publisher>The University of Auckland, Bioengineering Institute</dc:publisher>
<cmeta:comment rdf:resource="rdf:#11e8d270-3a86-4123-b21c-a800cea9c670"/>
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<dcterms:W3CDTF>2002-03-21T00:00:00+00:00</dcterms:W3CDTF>
</rdf:Description>
<rdf:Description rdf:about="rdf:#242b8f41-13f6-47c9-8cdb-0ac04f1218c5">
<dcterms:W3CDTF>2000-03</dcterms:W3CDTF>
</rdf:Description>
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<dcterms:modified rdf:resource="rdf:#08ffc2ef-27c5-4248-a828-d04361e115bd"/>
<rdf:value>
Added more metadata.
</rdf:value>
<cmeta:modifier rdf:resource="rdf:#2a66c8f9-9a21-447b-b93f-9913e5dc832d"/>
</rdf:Description>
<rdf:Description rdf:about="rdf:#bfb5711f-98fe-41b1-a7f5-b66ea97b1158">
<dc:title>Journal of General Physiology</dc:title>
</rdf:Description>
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<vCard:Given>Stephen</vCard:Given>
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<vCard:Other>L</vCard:Other>
</rdf:Description>
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<rdf:Description rdf:about="#colegrove_albrecht_friel_2000_version01">
<dc:title>
Quantitative analysis of mitochondrial Ca2+ uptake and release.
</dc:title>
<cmeta:bio_entity>sympathetic neuron</cmeta:bio_entity>
<cmeta:comment rdf:resource="rdf:#bed2e8da-84d2-4bc6-aa8e-b5a2e52b070a"/>
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<dcterms:W3CDTF>2003-04-09</dcterms:W3CDTF>
</rdf:Description>
<rdf:Description rdf:about="rdf:#f7f1a7a8-96f9-4b1e-b1b9-53e160951811">
<vCard:Given>Catherine</vCard:Given>
<vCard:Family>Lloyd</vCard:Family>
<vCard:Other>May</vCard:Other>
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<dc:creator rdf:resource="rdf:#60eb3f15-7edf-4ef7-8e03-18401794cc32"/>
<rdf:value>This is the CellML description of Colegrove et al's 2000 model of
mitochondrial Ca2+ uptake and release pathways in sympathetic neurons.</rdf:value>
</rdf:Description>
<rdf:Description rdf:about="rdf:#102b3c52-8a2c-4bc9-9e4d-0a6efe9e1407">
<dcterms:W3CDTF>2009-06-05T15:33:47+12:00</dcterms:W3CDTF>
</rdf:Description>
<rdf:Description rdf:about="rdf:#bf0bc8c5-41da-41a8-9215-4b2d40657a05">
<dcterms:W3CDTF>2003-03-28</dcterms:W3CDTF>
</rdf:Description>
<rdf:Description rdf:about="rdf:#784a653d-0e35-4c93-acc2-91fc946a3d53">
<vCard:Given>Meredith</vCard:Given>
<vCard:Family>Albrecht</vCard:Family>
<vCard:Other>A</vCard:Other>
</rdf:Description>
<rdf:Description rdf:about="rdf:#11e8d270-3a86-4123-b21c-a800cea9c670">
<dc:creator rdf:resource="rdf:#fc2db557-dd0b-490c-baad-a7683648f363"/>
<rdf:value/>
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<vCard:Given>Catherine</vCard:Given>
<vCard:Family>Lloyd</vCard:Family>
<vCard:Other>May</vCard:Other>
</rdf:Description>
<rdf:Description rdf:about="rdf:#7c904e32-a025-4122-9845-95fb0271af84">
<vCard:Given>David</vCard:Given>
<vCard:Family>Friel</vCard:Family>
<vCard:Other>D</vCard:Other>
</rdf:Description>
<rdf:Description rdf:about="rdf:#299ece5d-3d77-4dd3-932e-aa5308a309da">
<dcterms:modified rdf:resource="rdf:#07d373b1-f2e7-4c01-8b08-3fde0f368b11"/>
<rdf:value>
Added publication date information.
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<vCard:FN>Catherine Lloyd</vCard:FN>
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Changed the name and cmeta:id of the model to reflect the proper
spelling of Colegrove.
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<vCard:Given>James</vCard:Given>
<vCard:Family>Lawson</vCard:Family>
<vCard:Other>Richard</vCard:Other>
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<dcterms:W3CDTF>2002-07-18</dcterms:W3CDTF>
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<vCard:Given>Autumn</vCard:Given>
<vCard:Family>Cuellar</vCard:Family>
<vCard:Other>A</vCard:Other>
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<rdf:value>c.lloyd@auckland.ac.nz</rdf:value>
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<dc:creator rdf:resource="rdf:#66e8815f-2d77-46f0-b46a-a2919d8eaa70"/>
<dc:title>Quantitive Analysis of Mitochondrial Ca2+ Uptake and Release Pathways in Sympathetic Neurons Reconstruction of the Recovery after Depolarisation-evoked [Ca2+] Elevations</dc:title>
<bqs:volume>115</bqs:volume>
<bqs:first_page>371</bqs:first_page>
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<bqs:last_page>388</bqs:last_page>
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<rdf:value>updated curation status, removed reference link in documentation</rdf:value>
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<vCard:Given>Autumn</vCard:Given>
<vCard:Family>Cuellar</vCard:Family>
<vCard:Other>A</vCard:Other>
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<vCard:FN/>
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