- Author:
- neilstephen2001 <npar276@aucklanduni.ac.nz>
- Date:
- 2021-01-24 22:12:22+13:00
- Desc:
- adding OMEX archives to workspace
- Permanent Source URI:
- http://models.cellml.org/workspace/7f1/rawfile/2e65c2ad37afa20404292391879d154ca9ca5fbe/albrecht_colegrove_friel_2002/model/albrecht_colegrove_friel_2002.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="albrecht_colegrove_friel_2002" cmeta:id="albrecht_colegrove_friel_2002_version01">
<documentation xmlns="http://cellml.org/tmp-documentation">
<article>
<articleinfo>
<title>Differential Regulation of ER Ca2+ Uptake and Release Rates Accounts for Multiple Modes of Ca2+-induced Ca2+ Release</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 is consistently represented within the CellML but contains sets of algebraic equations that prevent the model from being solved in currently available software - 03/08.</para>
<para>ValidateCellML found unit inconsistencies in this model</para>
</section>
<sect1 id="sec_structure">
<title>Model Structure</title>
<para>
Calcium is an important signalling ion, and changes in Ca
<superscript>2+</superscript>
concentration ([Ca
<superscript>2+</superscript>
]) regulate diverse processes in many cellular compartments. In excitable cells, depolarisation-induced Ca
<superscript>2+</superscript>
entry increases [Ca
<superscript>2+</superscript>
]
<subscript>i</subscript>
, leading to secondary changes in [Ca
<superscript>2+</superscript>
] within organelles such as mitochondria and ER that regulate specific Ca
<superscript>2+</superscript>
-sensitive targets within these organelles. Although mitochondria accumulate Ca
<superscript>2+</superscript>
in response to depolarisation-evoked [Ca
<superscript>2+</superscript>
]
<subscript>i</subscript>
elevations (see
<ulink url="${HTML_EXMPL_COLEGROVE_MODEL}">
The Colegrove
<emphasis>et al</emphasis>
Model Of Mitochondrial Ca
<superscript>2+</superscript>
Uptake And Release, 2000
</ulink>
), the ER is also an important component in Ca
<superscript>2+</superscript>
signalling in virtually all non-muscle cells, and it has been described as either a Ca
<superscript>2+</superscript>
source or sink. Different modes of net ER Ca
<superscript>2+</superscript>
transport are expected to have very different effects on cytoplasmic and intraluminal Ca
<superscript>2+</superscript>
signals and on the processes they regulate (see
<ulink url="${HTML_EXMPL_ALBRECHT_MODEL1}">
The Albrecht
<emphasis>et al</emphasis>
Model Of Multiple Modes of Ca
<superscript>2+</superscript>
-induced Ca
<superscript>2+</superscript>
Release in Sympathetic Neurons, 2001
</ulink>
).
</para>
<para>
In a follow up study to their 2001 paper, Meredith A. Albrecht, Stephen L. Colegrove and David D. Friel have examined how differential regulation of ER Ca
<superscript>2+</superscript>
uptake and release rates accounts for multiple modes of Ca
<superscript>2+</superscript>
-induced Ca
<superscript>2+</superscript>
release. Three different macroscopic Ca
<superscript>2+</superscript>
fluxes were modelled: J
<subscript>SERCA</subscript>
, the rate of Ca
<superscript>2+</superscript>
uptake via SR Ca-ATPases; J
<subscript>ICa</subscript>
, the total cytoplasmic Ca
<superscript>2+</superscript>
flux when SR Ca-ATPases are inhibited; and J
<subscript>pm</subscript>
, the rate of Ca
<superscript>2+</superscript>
extrusion across the plasma membrane. One additional flux J
<subscript>release</subscript>
was calculated from the difference between J
<subscript>ICa</subscript>
and J
<subscript>pm</subscript>
(see
<xref linkend="fig_cell_diagram" />
below). 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/119/3/211">
Differential Regulation of ER Ca
<superscript>2+</superscript>
Uptake and Release Rates Accounts for Multiple Modes of Ca
<superscript>2+</superscript>
-induced Ca
<superscript>2+</superscript>
Release
</ulink>
, Meredith A. Albrecht, Stephen L. Colegrove and David D. Friel, 2002,
<ulink url="http://www.jgp.org/">
<emphasis>The Journal Of General Physiology</emphasis>
</ulink>
, 119, 211-233. (
<ulink url="http://www.jgp.org/cgi/content/full/119/3/211">Full text</ulink>
and
<ulink url="http://www.jgp.org/cgi/reprint/119/3/211.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=11865019&dopt=Abstract">PubMed ID: 11865019</ulink>
</para>
<informalfigure float="0" id="fig_cell_diagram">
<mediaobject>
<imageobject>
<objectinfo>
<title>cell schematic for the model</title>
</objectinfo>
<imagedata fileref="albrecht_2002.png" />
</imageobject>
</mediaobject>
<caption>
Schematic of the model indicating Ca
<superscript>2+</superscript>
compartmentation in the extracellular matrix, cytosol and the ER and pathways for Ca
<superscript>2+</superscript>
ion movement between the compartments.
</caption>
</informalfigure>
</sect1>
</article>
</documentation>
<units name="micromolar_per_second">
<unit units="micromolar" />
<unit exponent="-1.0" units="second" />
</units>
<units name="millimolar">
<unit prefix="micro" units="mole" />
<unit exponent="-1.0" units="litre" />
</units>
<units name="picoA">
<unit prefix="pico" units="ampere" />
</units>
<units name="coulomb_per_millimole">
<unit exponent="-1.0" prefix="milli" units="mole" />
<unit units="coulomb" />
</units>
<units name="micro_litre">
<unit prefix="micro" units="litre" />
</units>
<units name="nanomolar">
<unit prefix="nano" units="mole" />
<unit exponent="-1.0" units="litre" />
</units>
<units name="micromolar">
<unit prefix="micro" units="mole" />
<unit exponent="-1.0" units="litre" />
</units>
<units name="millivolt">
<unit prefix="milli" units="volt" />
</units>
<units name="nanomolar_per_second">
<unit exponent="-1.0" units="second" />
<unit units="nanomolar" />
</units>
<units name="per_second">
<unit exponent="-1.0" units="second" />
</units>
<component name="environment" cmeta:id="submodel_0">
<variable cmeta:id="environment.time" name="time" public_interface="out" units="second" />
</component>
<component name="cytoplasmic_calcium" cmeta:id="submodel_1">
<variable cmeta:id="cytoplasmic_calcium.Ca_i" name="Ca_i" public_interface="out" units="nanomolar" />
<variable cmeta:id="cytoplasmic_calcium.J_i" name="J_i" units="nanomolar_per_second" />
<variable cmeta:id="cytoplasmic_calcium.J_ER" name="J_ER" public_interface="in" units="nanomolar_per_second" />
<variable cmeta:id="cytoplasmic_calcium.J_pm" name="J_pm" public_interface="in" units="nanomolar_per_second" />
<variable cmeta:id="cytoplasmic_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 />
<ci>J_i</ci>
</apply>
</apply>
<apply id="J_i_calculation">
<eq />
<ci>J_i</ci>
<apply>
<plus />
<ci>J_pm</ci>
<ci>J_ER</ci>
</apply>
</apply>
</math>
</component>
<component name="intraluminal_calcium" cmeta:id="submodel_2">
<variable cmeta:id="intraluminal_calcium.Ca_ER" name="Ca_ER" public_interface="out" units="nanomolar" />
<variable cmeta:id="intraluminal_calcium.v_ER" name="v_ER" units="micro_litre" />
<variable cmeta:id="intraluminal_calcium.k_ER" name="k_ER" units="dimensionless" />
<variable cmeta:id="intraluminal_calcium.Ca_ER_init" name="Ca_ER_init" units="nanomolar" />
<variable cmeta:id="intraluminal_calcium.Ca_i" name="Ca_i" public_interface="in" units="nanomolar" />
<variable cmeta:id="intraluminal_calcium.v_i" name="v_i" public_interface="in" units="micro_litre" />
<variable cmeta:id="intraluminal_calcium.k_i" name="k_i" public_interface="in" units="dimensionless" />
<variable cmeta:id="intraluminal_calcium.J_ER" name="J_ER" public_interface="in" units="nanomolar_per_second" />
<variable cmeta:id="intraluminal_calcium.P_ER" name="P_ER" public_interface="in" units="per_second" />
<variable cmeta:id="intraluminal_calcium.J_SERCA" name="J_SERCA" public_interface="in" units="nanomolar_per_second" />
<variable cmeta:id="intraluminal_calcium.time" name="time" public_interface="in" units="second" />
<math xmlns="http://www.w3.org/1998/Math/MathML">
<apply id="Ca_ER_diff_eq">
<eq />
<apply>
<diff />
<bvar>
<ci>time</ci>
</bvar>
<ci>Ca_ER</ci>
</apply>
<apply>
<times />
<ci>J_ER</ci>
<apply>
<divide />
<apply>
<times />
<ci>v_i</ci>
<ci>k_i</ci>
</apply>
<apply>
<times />
<ci>v_ER</ci>
<ci>k_ER</ci>
</apply>
</apply>
</apply>
</apply>
<apply id="Ca_ER_init_calculation">
<eq />
<ci>Ca_ER_init</ci>
<apply>
<plus />
<ci>Ca_i</ci>
<apply>
<divide />
<apply>
<times />
<ci>J_SERCA</ci>
<ci>Ca_i</ci>
</apply>
<apply>
<times />
<ci>P_ER</ci>
<apply>
<divide />
<ci>Ca_i</ci>
<ci>v_i</ci>
</apply>
</apply>
</apply>
</apply>
</apply>
</math>
</component>
<component name="total_cytoplasmic_Ca_flux" cmeta:id="submodel_3">
<variable cmeta:id="total_cytoplasmic_Ca_flux.J_ICa" name="J_ICa" public_interface="out" units="nanomolar_per_second" />
<variable cmeta:id="total_cytoplasmic_Ca_flux.v_i" name="v_i" public_interface="out" units="micro_litre" />
<variable cmeta:id="total_cytoplasmic_Ca_flux.k_i" name="k_i" public_interface="out" units="dimensionless" />
<variable cmeta:id="total_cytoplasmic_Ca_flux.F" initial_value="96.5" name="F" units="coulomb_per_millimole" />
<variable cmeta:id="total_cytoplasmic_Ca_flux.I_Ca" name="I_Ca" units="picoA" />
<variable cmeta:id="total_cytoplasmic_Ca_flux.time" name="time" public_interface="in" units="second" />
<math xmlns="http://www.w3.org/1998/Math/MathML">
<apply id="J_ICa_calculation">
<eq />
<ci>J_ICa</ci>
<apply>
<divide />
<ci>I_Ca</ci>
<apply>
<times />
<cn xmlns:cellml="http://www.cellml.org/cellml/1.0#" cellml:units="dimensionless">2.0</cn>
<ci>F</ci>
<ci>v_i</ci>
<ci>k_i</ci>
</apply>
</apply>
</apply>
</math>
</component>
<component name="Ca_extrusion_across_the_plasma_membrane" cmeta:id="submodel_4">
<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_extru" name="J_extru" units="nanomolar_per_second" />
<variable cmeta:id="Ca_extrusion_across_the_plasma_membrane.k_leak_pm" initial_value="0.00000015" name="k_leak_pm" units="per_second" />
<variable cmeta:id="Ca_extrusion_across_the_plasma_membrane.Vmax_extru" initial_value="25.0" name="Vmax_extru" units="nanomolar_per_second" />
<variable cmeta:id="Ca_extrusion_across_the_plasma_membrane.EC50_extru" initial_value="386.0" name="EC50_extru" units="nanomolar" />
<variable cmeta:id="Ca_extrusion_across_the_plasma_membrane.n_extru" initial_value="2.4" name="n_extru" units="dimensionless" />
<variable cmeta:id="Ca_extrusion_across_the_plasma_membrane.Ca_o" initial_value="2.0" name="Ca_o" units="millimolar" />
<variable cmeta:id="Ca_extrusion_across_the_plasma_membrane.J_ICa" name="J_ICa" public_interface="in" units="nanomolar_per_second" />
<variable cmeta:id="Ca_extrusion_across_the_plasma_membrane.k_i" name="k_i" public_interface="in" units="dimensionless" />
<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_extru</ci>
<ci>J_ICa</ci>
</apply>
</apply>
<apply id="J_extru_calculation">
<eq />
<ci>J_extru</ci>
<apply>
<times />
<apply>
<power />
<ci>k_i</ci>
<cn xmlns:cellml="http://www.cellml.org/cellml/1.0#" cellml:units="dimensionless">-1.0</cn>
</apply>
<apply>
<plus />
<apply>
<times />
<ci>k_leak_pm</ci>
<apply>
<minus />
<ci>Ca_i</ci>
<ci>Ca_o</ci>
</apply>
</apply>
<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>
</apply>
</apply>
</math>
</component>
<component name="Ca_uptake_by_SR_Ca_ATPase" cmeta:id="submodel_5">
<variable cmeta:id="Ca_uptake_by_SR_Ca_ATPase.J_SERCA" name="J_SERCA" public_interface="out" units="nanomolar_per_second" />
<variable cmeta:id="Ca_uptake_by_SR_Ca_ATPase.Vmax_SERCA" initial_value="2146.0" name="Vmax_SERCA" units="nanomolar_per_second" />
<variable cmeta:id="Ca_uptake_by_SR_Ca_ATPase.EC50_SERCA" initial_value="30.3" name="EC50_SERCA" units="micromolar" />
<variable cmeta:id="Ca_uptake_by_SR_Ca_ATPase.n_SERCA" initial_value="2.5" name="n_SERCA" units="dimensionless" />
<variable cmeta:id="Ca_uptake_by_SR_Ca_ATPase.k_i" name="k_i" public_interface="in" units="dimensionless" />
<variable cmeta:id="Ca_uptake_by_SR_Ca_ATPase.Ca_i" name="Ca_i" public_interface="in" units="nanomolar" />
<variable cmeta:id="Ca_uptake_by_SR_Ca_ATPase.time" name="time" public_interface="in" units="second" />
<math xmlns="http://www.w3.org/1998/Math/MathML">
<apply id="J_SERCA_calculation">
<eq />
<ci>J_SERCA</ci>
<apply>
<divide />
<ci>Vmax_SERCA</ci>
<apply>
<times />
<ci>k_i</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_SERCA</ci>
<ci>Ca_i</ci>
</apply>
<ci>n_SERCA</ci>
</apply>
</apply>
</apply>
</apply>
</apply>
</math>
</component>
<component name="ER_Ca_release" cmeta:id="submodel_6">
<variable cmeta:id="ER_Ca_release.J_ER" name="J_ER" public_interface="out" units="nanomolar_per_second" />
<variable cmeta:id="ER_Ca_release.P_ER" name="P_ER" public_interface="out" units="per_second" />
<variable cmeta:id="ER_Ca_release.P_basal" initial_value="0.009" name="P_basal" units="per_second" />
<variable cmeta:id="ER_Ca_release.Pmax_RyR" initial_value="0.05" name="Pmax_RyR" units="per_second" />
<variable cmeta:id="ER_Ca_release.EC50_RyR" initial_value="2641.0" name="EC50_RyR" units="nanomolar" />
<variable cmeta:id="ER_Ca_release.n_RyR" initial_value="0.96" name="n_RyR" units="dimensionless" />
<variable cmeta:id="ER_Ca_release.J_release" name="J_release" units="nanomolar_per_second" />
<variable cmeta:id="ER_Ca_release.J_SERCA" name="J_SERCA" public_interface="in" units="nanomolar_per_second" />
<variable cmeta:id="ER_Ca_release.v_i" name="v_i" public_interface="in" units="micro_litre" />
<variable cmeta:id="ER_Ca_release.k_i" name="k_i" public_interface="in" units="dimensionless" />
<variable cmeta:id="ER_Ca_release.Ca_i" name="Ca_i" public_interface="in" units="nanomolar" />
<variable cmeta:id="ER_Ca_release.Ca_ER" name="Ca_ER" public_interface="in" units="nanomolar" />
<variable cmeta:id="ER_Ca_release.time" name="time" public_interface="in" units="second" />
<math xmlns="http://www.w3.org/1998/Math/MathML">
<apply id="J_release_calculation">
<eq />
<ci>J_release</ci>
<apply>
<divide />
<apply>
<times />
<ci>P_ER</ci>
<apply>
<minus />
<ci>Ca_i</ci>
<ci>Ca_ER</ci>
</apply>
</apply>
<apply>
<times />
<ci>v_i</ci>
<ci>k_i</ci>
</apply>
</apply>
</apply>
<apply id="J_ER_calculation">
<eq />
<ci>J_ER</ci>
<apply>
<plus />
<ci>J_SERCA</ci>
<ci>J_release</ci>
</apply>
</apply>
<apply id="P_ER_v_i_calculation">
<eq />
<ci>P_ER</ci>
<apply>
<times />
<ci>v_i</ci>
<apply>
<plus />
<ci>P_basal</ci>
<apply>
<divide />
<ci>Pmax_RyR</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_RyR</ci>
<ci>Ca_i</ci>
</apply>
<ci>n_RyR</ci>
</apply>
</apply>
</apply>
</apply>
</apply>
</apply>
</math>
</component>
<connection>
<map_components component_1="cytoplasmic_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="Ca_uptake_by_SR_Ca_ATPase" component_2="ER_Ca_release" />
<map_variables variable_1="J_SERCA" variable_2="J_SERCA" />
</connection>
<connection>
<map_components component_1="Ca_uptake_by_SR_Ca_ATPase" component_2="intraluminal_calcium" />
<map_variables variable_1="J_SERCA" variable_2="J_SERCA" />
</connection>
<connection>
<map_components component_1="cytoplasmic_calcium" component_2="Ca_uptake_by_SR_Ca_ATPase" />
<map_variables variable_1="Ca_i" variable_2="Ca_i" />
</connection>
<connection>
<map_components component_1="ER_Ca_release" component_2="intraluminal_calcium" />
<map_variables variable_1="J_ER" variable_2="J_ER" />
<map_variables variable_1="P_ER" variable_2="P_ER" />
</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="environment" component_2="cytoplasmic_calcium" />
<map_variables variable_1="time" variable_2="time" />
</connection>
<connection>
<map_components component_1="Ca_extrusion_across_the_plasma_membrane" component_2="cytoplasmic_calcium" />
<map_variables variable_1="J_pm" variable_2="J_pm" />
</connection>
<connection>
<map_components component_1="cytoplasmic_calcium" component_2="ER_Ca_release" />
<map_variables variable_1="Ca_i" variable_2="Ca_i" />
</connection>
<connection>
<map_components component_1="environment" component_2="total_cytoplasmic_Ca_flux" />
<map_variables variable_1="time" variable_2="time" />
</connection>
<connection>
<map_components component_1="environment" component_2="ER_Ca_release" />
<map_variables variable_1="time" variable_2="time" />
</connection>
<connection>
<map_components component_1="total_cytoplasmic_Ca_flux" component_2="Ca_extrusion_across_the_plasma_membrane" />
<map_variables variable_1="J_ICa" variable_2="J_ICa" />
<map_variables variable_1="k_i" variable_2="k_i" />
</connection>
<connection>
<map_components component_1="environment" component_2="Ca_uptake_by_SR_Ca_ATPase" />
<map_variables variable_1="time" variable_2="time" />
</connection>
<connection>
<map_components component_1="intraluminal_calcium" component_2="ER_Ca_release" />
<map_variables variable_1="Ca_ER" variable_2="Ca_ER" />
</connection>
<connection>
<map_components component_1="total_cytoplasmic_Ca_flux" component_2="Ca_uptake_by_SR_Ca_ATPase" />
<map_variables variable_1="k_i" variable_2="k_i" />
</connection>
<connection>
<map_components component_1="cytoplasmic_calcium" component_2="intraluminal_calcium" />
<map_variables variable_1="Ca_i" variable_2="Ca_i" />
</connection>
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