- Author:
- neilstephen2001 <npar276@aucklanduni.ac.nz>
- Date:
- 2021-01-25 20:14:52+13:00
- Desc:
- adding OMEX archives to workspace
- Permanent Source URI:
- http://models.cellml.org/workspace/7f1/rawfile/28c2ad84a0934867149129508999a36c9d0fa1cf/colegrove_albrecht_friel_2000/model/colegrove_albrecht_friel_2000.cellml
<?xml version="1.0" encoding="UTF-8"?>
<model xmlns="http://www.cellml.org/cellml/1.1#" xmlns:cmeta="http://www.cellml.org/metadata/1.0#" xmlns:xlink="http://www.w3.org/1999/xlink" xmlns:rdf="http://www.w3.org/1999/02/22-rdf-syntax-ns#" xmlns:bqs="http://www.cellml.org/bqs/1.0#" xmlns:semsim="http://www.bhi.washington.edu/SemSim#" xmlns:dcterms="http://purl.org/dc/terms/" xmlns:vCard="http://www.w3.org/2001/vcard-rdf/3.0#" name="colegrove_albrecht_friel_2000" cmeta:id="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>
<units name="micro_litre">
<unit prefix="micro" units="litre" />
</units>
<units name="nanomolar">
<unit exponent="-1.0" units="litre" />
<unit prefix="nano" units="mole" />
</units>
<units name="per_second">
<unit exponent="-1.0" units="second" />
</units>
<units name="nanomolar_per_second">
<unit exponent="-1.0" units="second" />
<unit units="nanomolar" />
</units>
<units name="millivolt">
<unit prefix="milli" units="volt" />
</units>
<units name="micromolar">
<unit exponent="-1.0" units="litre" />
<unit prefix="micro" units="mole" />
</units>
<units name="micromolar_per_second">
<unit exponent="-1.0" units="second" />
<unit units="micromolar" />
</units>
<component name="environment" cmeta:id="submodel_0">
<variable cmeta:id="environment.time" name="time" public_interface="out" units="second" />
</component>
<component name="Ca_extrusion_across_the_plasma_membrane" cmeta:id="submodel_1">
<variable cmeta:id="Ca_extrusion_across_the_plasma_membrane.J_pm" name="J_pm" public_interface="out" units="nanomolar_per_second" />
<variable cmeta:id="Ca_extrusion_across_the_plasma_membrane.J_leak" name="J_leak" units="nanomolar_per_second" />
<variable cmeta:id="Ca_extrusion_across_the_plasma_membrane.J_extru" name="J_extru" units="nanomolar_per_second" />
<variable cmeta:id="Ca_extrusion_across_the_plasma_membrane.k_leak" initial_value="0.00000037" name="k_leak" units="per_second" />
<variable cmeta:id="Ca_extrusion_across_the_plasma_membrane.Vmax_extru" initial_value="28.3" name="Vmax_extru" units="nanomolar_per_second" />
<variable cmeta:id="Ca_extrusion_across_the_plasma_membrane.EC50_extru" initial_value="378.8" name="EC50_extru" units="nanomolar" />
<variable cmeta:id="Ca_extrusion_across_the_plasma_membrane.n_extru" initial_value="1.8" name="n_extru" units="dimensionless" />
<variable cmeta:id="Ca_extrusion_across_the_plasma_membrane.Ca_o" initial_value="0.002" name="Ca_o" units="nanomolar" />
<variable cmeta:id="Ca_extrusion_across_the_plasma_membrane.Ca_i" name="Ca_i" public_interface="in" units="nanomolar" />
<variable cmeta:id="Ca_extrusion_across_the_plasma_membrane.time" name="time" public_interface="in" units="second" />
<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 xmlns:cellml="http://www.cellml.org/cellml/1.0#" 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" cmeta:id="submodel_2">
<variable cmeta:id="mitochondrial_Ca_uptake.J_uni" name="J_uni" public_interface="out" units="nanomolar_per_second" />
<variable cmeta:id="mitochondrial_Ca_uptake.kuni_max" initial_value="75.9" name="kuni_max" units="per_second" />
<variable cmeta:id="mitochondrial_Ca_uptake.EC50_uni" initial_value="10.0" name="EC50_uni" units="micromolar" />
<variable cmeta:id="mitochondrial_Ca_uptake.n_uni" initial_value="2.0" name="n_uni" units="dimensionless" />
<variable cmeta:id="mitochondrial_Ca_uptake.Ca_i" name="Ca_i" public_interface="in" units="nanomolar" />
<variable cmeta:id="mitochondrial_Ca_uptake.time" name="time" public_interface="in" units="second" />
<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 xmlns:cellml="http://www.cellml.org/cellml/1.0#" 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" cmeta:id="submodel_3">
<variable cmeta:id="mitochondrial_Ca_release.J_NaCa" name="J_NaCa" public_interface="out" units="nanomolar_per_second" />
<variable cmeta:id="mitochondrial_Ca_release.Ca_inhibited_J_NaCa" name="Ca_inhibited_J_NaCa" public_interface="out" units="nanomolar_per_second" />
<variable cmeta:id="mitochondrial_Ca_release.J_mito" name="J_mito" public_interface="out" units="nanomolar_per_second" />
<variable cmeta:id="mitochondrial_Ca_release.Vmax_NaCa" initial_value="-35.0" name="Vmax_NaCa" units="nanomolar_per_second" />
<variable cmeta:id="mitochondrial_Ca_release.EC50_NaCa" initial_value="307.0" name="EC50_NaCa" units="nanomolar" />
<variable cmeta:id="mitochondrial_Ca_release.n_inhib" initial_value="6.0" name="n_inhib" units="dimensionless" />
<variable cmeta:id="mitochondrial_Ca_release.k_inhib" initial_value="500.0" name="k_inhib" units="nanomolar" />
<variable cmeta:id="mitochondrial_Ca_release.delta_Ca_i" name="delta_Ca_i" units="dimensionless" />
<variable cmeta:id="mitochondrial_Ca_release.J_uni" name="J_uni" public_interface="in" units="nanomolar_per_second" />
<variable cmeta:id="mitochondrial_Ca_release.Ca_i" name="Ca_i" public_interface="in" units="nanomolar" />
<variable cmeta:id="mitochondrial_Ca_release.Ca_m" name="Ca_m" public_interface="in" units="nanomolar" />
<variable cmeta:id="mitochondrial_Ca_release.time" name="time" public_interface="in" units="second" />
<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 xmlns:cellml="http://www.cellml.org/cellml/1.0#" 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 xmlns:cellml="http://www.cellml.org/cellml/1.0#" 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 xmlns:cellml="http://www.cellml.org/cellml/1.0#" cellml:units="dimensionless">1.0</cn>
<apply>
<divide />
<cn xmlns:cellml="http://www.cellml.org/cellml/1.0#" cellml:units="dimensionless">1.0</cn>
<apply>
<minus />
<cn xmlns:cellml="http://www.cellml.org/cellml/1.0#" 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" cmeta:id="submodel_4">
<variable cmeta:id="intracellular_calcium.Ca_i" name="Ca_i" public_interface="out" units="nanomolar" />
<variable cmeta:id="intracellular_calcium.J_pm" name="J_pm" public_interface="in" units="nanomolar_per_second" />
<variable cmeta:id="intracellular_calcium.J_mito" name="J_mito" public_interface="in" units="nanomolar_per_second" />
<variable cmeta:id="intracellular_calcium.time" name="time" public_interface="in" units="second" />
<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" cmeta:id="submodel_5">
<variable cmeta:id="mitochondrial_calcium.Ca_m" name="Ca_m" public_interface="out" units="nanomolar" />
<variable cmeta:id="mitochondrial_calcium.gamma" initial_value="2.0" name="gamma" units="dimensionless" />
<variable cmeta:id="mitochondrial_calcium.v_m" name="v_m" units="micro_litre" />
<variable cmeta:id="mitochondrial_calcium.k_m" name="k_m" units="dimensionless" />
<variable cmeta:id="mitochondrial_calcium.v_i" name="v_i" units="micro_litre" />
<variable cmeta:id="mitochondrial_calcium.k_i" name="k_i" units="dimensionless" />
<variable cmeta:id="mitochondrial_calcium.J_mito" name="J_mito" public_interface="in" units="nanomolar_per_second" />
<variable cmeta:id="mitochondrial_calcium.time" name="time" public_interface="in" units="second" />
<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_1="mitochondrial_Ca_release" component_2="intracellular_calcium" />
<map_variables variable_1="J_mito" variable_2="J_mito" />
</connection>
<connection>
<map_components component_1="environment" component_2="mitochondrial_calcium" />
<map_variables variable_1="time" variable_2="time" />
</connection>
<connection>
<map_components component_1="mitochondrial_calcium" component_2="mitochondrial_Ca_release" />
<map_variables variable_1="Ca_m" variable_2="Ca_m" />
</connection>
<connection>
<map_components component_1="intracellular_calcium" component_2="mitochondrial_Ca_release" />
<map_variables variable_1="Ca_i" variable_2="Ca_i" />
</connection>
<connection>
<map_components component_1="Ca_extrusion_across_the_plasma_membrane" component_2="intracellular_calcium" />
<map_variables variable_1="J_pm" variable_2="J_pm" />
</connection>
<connection>
<map_components component_1="intracellular_calcium" component_2="Ca_extrusion_across_the_plasma_membrane" />
<map_variables variable_1="Ca_i" variable_2="Ca_i" />
</connection>
<connection>
<map_components component_1="environment" component_2="mitochondrial_Ca_release" />
<map_variables variable_1="time" variable_2="time" />
</connection>
<connection>
<map_components component_1="mitochondrial_Ca_release" component_2="mitochondrial_calcium" />
<map_variables variable_1="J_mito" variable_2="J_mito" />
</connection>
<connection>
<map_components component_1="environment" component_2="Ca_extrusion_across_the_plasma_membrane" />
<map_variables variable_1="time" variable_2="time" />
</connection>
<connection>
<map_components component_1="mitochondrial_Ca_uptake" component_2="mitochondrial_Ca_release" />
<map_variables variable_1="J_uni" variable_2="J_uni" />
</connection>
<connection>
<map_components component_1="environment" component_2="mitochondrial_Ca_uptake" />
<map_variables variable_1="time" variable_2="time" />
</connection>
<connection>
<map_components component_1="environment" component_2="intracellular_calcium" />
<map_variables variable_1="time" variable_2="time" />
</connection>
<connection>
<map_components component_1="intracellular_calcium" component_2="mitochondrial_Ca_uptake" />
<map_variables variable_1="Ca_i" variable_2="Ca_i" />
</connection>
</model>
