- Author:
- rcai987 <devnull@localhost>
- Date:
- 2015-01-14 13:08:21+13:00
- Desc:
- Added annotations to colegrove_albrecht_friel_2000_version01 model
- Permanent Source URI:
- https://models.cellml.org/workspace/colegrove_albrecht_friel_2000/rawfile/fabf5900b6806d5f8bbcc9d46ddf4313165ae1da/colegrove_albrecht_friel_2000.cellml
<?xml version="1.0"?>
<!-- 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#" xml:base="file:///H:/colegrove_albrecht_friel_2000/colegrove_albrecht_friel_2000.cellml" 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 exponent="-1" units="second"/>
</units>
<units name="millivolt">
<unit prefix="milli" units="volt"/>
</units>
<units name="micromolar">
<unit prefix="micro" units="mole"/>
<unit exponent="-1" units="litre"/>
</units>
<units name="nanomolar">
<unit prefix="nano" units="mole"/>
<unit exponent="-1" units="litre"/>
</units>
<units name="nanomolar_per_second">
<unit units="nanomolar"/>
<unit exponent="-1" units="second"/>
</units>
<units name="micromolar_per_second">
<unit units="micromolar"/>
<unit exponent="-1" units="second"/>
</units>
<units name="micro_litre">
<unit prefix="micro" units="litre"/>
</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 name="time" public_interface="out" units="second"/>
</component>
<component cmeta:id="id_00001" name="Ca_extrusion_across_the_plasma_membrane">
<variable cmeta:id="id_00035" name="J_pm" public_interface="out" units="nanomolar_per_second"/>
<variable cmeta:id="id_00002" name="J_leak" units="nanomolar_per_second"/>
<variable cmeta:id="id_00034" name="J_extru" units="nanomolar_per_second"/>
<variable cmeta:id="id_00003" initial_value="0.00000037" name="k_leak" units="per_second"/>
<variable cmeta:id="id_00033" initial_value="28.3" name="Vmax_extru" units="nanomolar_per_second"/>
<variable cmeta:id="id_00031" initial_value="378.8" name="EC50_extru" units="nanomolar"/>
<variable cmeta:id="id_00032" initial_value="1.8" name="n_extru" units="dimensionless"/>
<variable cmeta:id="id_00004" initial_value="0.002" name="Ca_o" units="nanomolar"/>
<variable cmeta:id="id_00005" name="Ca_i" public_interface="in" units="nanomolar"/>
<variable 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 cmeta:id="id_00011" name="mitochondrial_Ca_uptake">
<variable cmeta:id="id_00012" name="J_uni" public_interface="out" units="nanomolar_per_second"/>
<variable cmeta:id="id_00013" initial_value="75.9" name="kuni_max" units="per_second"/>
<variable cmeta:id="id_00014" initial_value="10.0" name="EC50_uni" units="micromolar"/>
<variable cmeta:id="id_00015" initial_value="2.0" name="n_uni" units="dimensionless"/>
<variable cmeta:id="id_00010" name="Ca_i" public_interface="in" units="nanomolar"/>
<variable 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 cmeta:id="id_00016" name="mitochondrial_Ca_release">
<variable cmeta:id="id_00017" name="J_NaCa" public_interface="out" units="nanomolar_per_second"/>
<variable cmeta:id="id_00018" name="Ca_inhibited_J_NaCa" public_interface="out" units="nanomolar_per_second"/>
<variable cmeta:id="id_00030" name="J_mito" public_interface="out" units="nanomolar_per_second"/>
<variable cmeta:id="id_00019" initial_value="-35.0" name="Vmax_NaCa" units="nanomolar_per_second"/>
<variable cmeta:id="id_00020" initial_value="307.0" name="EC50_NaCa" units="nanomolar"/>
<variable cmeta:id="id_00021" initial_value="6.0" name="n_inhib" units="dimensionless"/>
<variable cmeta:id="id_00022" initial_value="500.0" name="k_inhib" units="nanomolar"/>
<variable cmeta:id="id_00023" name="delta_Ca_i" units="dimensionless"/>
<variable cmeta:id="id_00024" name="J_uni" public_interface="in" units="nanomolar_per_second"/>
<variable cmeta:id="id_00025" name="Ca_i" public_interface="in" units="nanomolar"/>
<variable cmeta:id="id_00026" name="Ca_m" public_interface="in" units="nanomolar"/>
<variable 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 cmeta:id="id_00006" name="intracellular_calcium">
<variable cmeta:id="id_00007" initial_value="0.002" name="Ca_i" public_interface="out" units="nanomolar"/>
<variable name="J_pm" public_interface="in" units="nanomolar_per_second"/>
<variable cmeta:id="id_00029" name="J_mito" public_interface="in" units="nanomolar_per_second"/>
<variable 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 cmeta:id="id_00008" name="mitochondrial_calcium">
<variable cmeta:id="id_00009" initial_value="50.0e-9" name="Ca_m" public_interface="out" units="nanomolar"/>
<variable cmeta:id="id_00027" initial_value="2.0" name="gamma" units="dimensionless"/>
<!-- <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="dimensionless" name="k_i"/> -->
<variable cmeta:id="id_00028" name="J_mito" public_interface="in" units="nanomolar_per_second"/>
<variable 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>
</math>
</component>
<connection>
<map_components component_1="Ca_extrusion_across_the_plasma_membrane" component_2="environment"/>
<map_variables variable_1="time" variable_2="time"/>
</connection>
<connection>
<map_components component_1="mitochondrial_Ca_uptake" component_2="environment"/>
<map_variables variable_1="time" variable_2="time"/>
</connection>
<connection>
<map_components component_1="mitochondrial_Ca_release" component_2="environment"/>
<map_variables variable_1="time" variable_2="time"/>
</connection>
<connection>
<map_components component_1="intracellular_calcium" component_2="environment"/>
<map_variables variable_1="time" variable_2="time"/>
</connection>
<connection>
<map_components component_1="mitochondrial_calcium" component_2="environment"/>
<map_variables variable_1="time" variable_2="time"/>
</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"/>
<map_variables variable_1="Ca_i" variable_2="Ca_i"/>
</connection>
<connection>
<map_components component_1="mitochondrial_Ca_uptake" component_2="intracellular_calcium"/>
<map_variables variable_1="Ca_i" variable_2="Ca_i"/>
</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="mitochondrial_Ca_release" component_2="intracellular_calcium"/>
<map_variables variable_1="J_mito" variable_2="J_mito"/>
<map_variables variable_1="Ca_i" variable_2="Ca_i"/>
</connection>
<connection>
<map_components component_1="mitochondrial_Ca_release" component_2="mitochondrial_calcium"/>
<map_variables variable_1="Ca_m" variable_2="Ca_m"/>
<map_variables variable_1="J_mito" variable_2="J_mito"/>
</connection>
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