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Quantitive Analysis of Mitochondrial Ca2+ Uptake and Release Pathways in Sympathetic Neurons Reconstruction of the Recovery after Depolarisation-evoked [Ca2+] Elevations
The CellML code.
<!-- 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:vCard="http://www.w3.org/2001/vcard-rdf/3.0#" xmlns:dcterms="http://purl.org/dc/terms/" xmlns:cellml="http://www.cellml.org/cellml/1.0#" xmlns:bqs="http://www.cellml.org/bqs/1.0#" xmlns:rdf="http://www.w3.org/1999/02/22-rdf-syntax-ns#" xmlns:dc="http://purl.org/dc/elements/1.1/" xmlns:cmeta="http://www.cellml.org/metadata/1.0#" xmlns="http://www.cellml.org/cellml/1.0#" 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 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>
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>
<ulink url="http://www.jgp.org/cgi/content/abstract/115/3/371">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>
</ulink>, Stephen L. Colegrove, Meredith A. Albrecht and David D. Friel, 2000, <ulink url="http://www.jgp.org/">
<emphasis>The Journal Of General Physiology</emphasis>
</ulink>, 115, 371-388. (<ulink url="http://www.jgp.org/cgi/content/full/115/3/371">Full text</ulink> and <ulink url="http://www.jgp.org/cgi/reprint/115/3/371.pdf">PDF</ulink> versions of the article are available for Journal Members on the JGP website.) <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="../images/colegrove_model_2000/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:Bag>
<rdf:Seq rdf:about="rdf:#9a684b74-16af-46ac-9e9b-d88c51828e2f">
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<rdf:Description rdf:about="rdf:#349b78ad-3f02-4edf-9190-19487e3cba3b">
<vCard:Given>Stephen</vCard:Given>
<vCard:Family>Colegrove</vCard:Family>
<vCard:Other>L</vCard:Other>
</rdf:Description>
<rdf:Description rdf:about="rdf:#08ffc2ef-27c5-4248-a828-d04361e115bd">
<dcterms:W3CDTF>2002-07-18</dcterms:W3CDTF>
</rdf:Description>
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<vCard:Given>Autumn</vCard:Given>
<vCard:Family>Cuellar</vCard:Family>
<vCard:Other>A</vCard:Other>
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<dc:creator rdf:resource="rdf:#38bd93ef-8c36-4594-8694-e2ab90027375" />
<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:#bf0bc8c5-41da-41a8-9215-4b2d40657a05">
<dcterms:W3CDTF>2003-03-28</dcterms:W3CDTF>
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<dcterms:W3CDTF>2000-03</dcterms:W3CDTF>
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<vCard:Given>Catherine</vCard:Given>
<vCard:Family>Lloyd</vCard:Family>
<vCard:Other>May</vCard:Other>
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<rdf:value>
Changed the name and cmeta:id of the model to reflect the proper
spelling of Colegrove.
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<vCard:Given>Meredith</vCard:Given>
<vCard:Family>Albrecht</vCard:Family>
<vCard:Other>A</vCard:Other>
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<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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Added more metadata.
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<vCard:Given>David</vCard:Given>
<vCard:Family>Friel</vCard:Family>
<vCard:Other>D</vCard:Other>
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<vCard:Given>Catherine</vCard:Given>
<vCard:Family>Lloyd</vCard:Family>
<vCard:Other>May</vCard:Other>
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<rdf:Description rdf:about="rdf:#2c462796-f403-4309-95cf-af5458d55f4d">
<vCard:Orgname>The University of Auckland</vCard:Orgname>
<vCard:Orgunit>The Bioengineering Institute</vCard:Orgunit>
</rdf:Description>
<rdf:Description rdf:about="rdf:#802dd7eb-eb02-41c5-9257-463e7a0dad2e">
<vCard:Given>Autumn</vCard:Given>
<vCard:Family>Cuellar</vCard:Family>
<vCard:Other>A</vCard:Other>
</rdf:Description>
<rdf:Description rdf:about="rdf:#d4b9f6c4-9dab-4882-b5d5-ee366dfb95df">
<rdf:type rdf:resource="http://www.cellml.org/bqs/1.0#Person" />
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<rdf:Description rdf:about="rdf:#38bd93ef-8c36-4594-8694-e2ab90027375">
<vCard:FN>Catherine Lloyd</vCard:FN>
</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.
</rdf:value>
<cmeta:modifier rdf:resource="rdf:#a6189788-adf5-4375-8624-99a5edb6bc8c" />
</rdf:Description>
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:vCard="http://www.w3.org/2001/vcard-rdf/3.0#" xmlns:dcterms="http://purl.org/dc/terms/" xmlns:cellml="http://www.cellml.org/cellml/1.0#" xmlns:bqs="http://www.cellml.org/bqs/1.0#" xmlns:rdf="http://www.w3.org/1999/02/22-rdf-syntax-ns#" xmlns:dc="http://purl.org/dc/elements/1.1/" xmlns:cmeta="http://www.cellml.org/metadata/1.0#" xmlns="http://www.cellml.org/cellml/1.0#" 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 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>
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>
<ulink url="http://www.jgp.org/cgi/content/abstract/115/3/371">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>
</ulink>, Stephen L. Colegrove, Meredith A. Albrecht and David D. Friel, 2000, <ulink url="http://www.jgp.org/">
<emphasis>The Journal Of General Physiology</emphasis>
</ulink>, 115, 371-388. (<ulink url="http://www.jgp.org/cgi/content/full/115/3/371">Full text</ulink> and <ulink url="http://www.jgp.org/cgi/reprint/115/3/371.pdf">PDF</ulink> versions of the article are available for Journal Members on the JGP website.) <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="../images/colegrove_model_2000/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:Bag>
<rdf:Seq rdf:about="rdf:#9a684b74-16af-46ac-9e9b-d88c51828e2f">
<rdf:li rdf:resource="rdf:#f3a57d12-c100-43a1-bf99-9dbff00ee238" />
<rdf:li rdf:resource="rdf:#d4b9f6c4-9dab-4882-b5d5-ee366dfb95df" />
<rdf:li rdf:resource="rdf:#b17f5d44-ca79-4b14-8b3a-df4f0ccaa58e" />
</rdf:Seq>
<rdf:Description rdf:about="rdf:#349b78ad-3f02-4edf-9190-19487e3cba3b">
<vCard:Given>Stephen</vCard:Given>
<vCard:Family>Colegrove</vCard:Family>
<vCard:Other>L</vCard:Other>
</rdf:Description>
<rdf:Description rdf:about="rdf:#08ffc2ef-27c5-4248-a828-d04361e115bd">
<dcterms:W3CDTF>2002-07-18</dcterms:W3CDTF>
</rdf:Description>
<rdf:Description rdf:about="rdf:#0bf7e943-4a72-40ff-a4fe-1320cad6a131">
<bqs:Pubmed_id>10694264</bqs:Pubmed_id>
<bqs:JournalArticle rdf:resource="rdf:#ae55ab67-8342-44ec-accc-87e096221be1" />
</rdf:Description>
<rdf:Description rdf:about="rdf:#fd12f9b8-0647-4332-ab69-e17e555a3ee9">
<vCard:Given>Autumn</vCard:Given>
<vCard:Family>Cuellar</vCard:Family>
<vCard:Other>A</vCard:Other>
</rdf:Description>
<rdf:Description rdf:about="rdf:#2a66c8f9-9a21-447b-b93f-9913e5dc832d">
<vCard:N rdf:resource="rdf:#b671c6ec-e206-4c0b-a47e-b1c6ef27a87a" />
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<dc:creator rdf:resource="rdf:#38bd93ef-8c36-4594-8694-e2ab90027375" />
<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:#bf0bc8c5-41da-41a8-9215-4b2d40657a05">
<dcterms:W3CDTF>2003-03-28</dcterms:W3CDTF>
</rdf:Description>
<rdf:Description rdf:about="rdf:#865d6cc1-2cc5-4456-b257-687db5dcf23d">
<dcterms:W3CDTF>2000-03</dcterms:W3CDTF>
</rdf:Description>
<rdf:Description rdf:about="rdf:#b17f5d44-ca79-4b14-8b3a-df4f0ccaa58e">
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<bqs:subject_type>keyword</bqs:subject_type>
<rdf:value rdf:resource="rdf:#c32af19e-6bc0-4535-b0e3-d355cba81348" />
</rdf:Description>
<rdf:Description rdf:about="rdf:#07d373b1-f2e7-4c01-8b08-3fde0f368b11">
<dcterms:W3CDTF>2003-04-09</dcterms:W3CDTF>
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<rdf:Description rdf:about="rdf:#945a3eb9-01d9-4da2-b658-976b365bccd9">
<vCard:Given>Catherine</vCard:Given>
<vCard:Family>Lloyd</vCard:Family>
<vCard:Other>May</vCard:Other>
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<rdf:Description rdf:about="rdf:#f4c255a9-864d-4a8d-a09a-e30f95033946">
<dcterms:modified rdf:resource="rdf:#bf0bc8c5-41da-41a8-9215-4b2d40657a05" />
<rdf:value>
Changed the name and cmeta:id of the model to reflect the proper
spelling of Colegrove.
</rdf:value>
<cmeta:modifier rdf:resource="rdf:#71687366-e5a3-455d-b9f0-9f31ef36fba4" />
</rdf:Description>
<rdf:Description rdf:about="rdf:#b8fb32d7-5689-4947-8dc3-04edfa9ffe04">
<vCard:Given>Meredith</vCard:Given>
<vCard:Family>Albrecht</vCard:Family>
<vCard:Other>A</vCard:Other>
</rdf:Description>
<rdf:Description rdf:about="rdf:#55703b79-c4e1-4484-89dd-90f1593dfdae">
<dcterms:W3CDTF>2002-03-21</dcterms:W3CDTF>
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<dc:creator rdf:resource="rdf:#9a684b74-16af-46ac-9e9b-d88c51828e2f" />
<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>
<bqs:Journal rdf:resource="rdf:#1d031703-1d15-4076-a937-451168880c24" />
<dcterms:issued rdf:resource="rdf:#865d6cc1-2cc5-4456-b257-687db5dcf23d" />
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