- Author:
- neilstephen2001 <npar276@aucklanduni.ac.nz>
- Date:
- 2021-01-26 14:35:03+13:00
- Desc:
- modifying rdf files
- Permanent Source URI:
- https://models.cellml.org/workspace/7f1/rawfile/4d6408caaf3e7b1b86d33d53d26105360ef95347/mosekilde_lading_yanchuk_maistrenko_2001/model/mosekilde_lading_yanchuk_maistrenko_2001.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="mosekilde_lading_yanchuk_maistrenko_2001" cmeta:id="mosekilde_lading_yanchuk_maistrenko_2001_version01">
<documentation xmlns="http://cellml.org/tmp-documentation">
<article>
<articleinfo>
<title>Bifurcation Structure of a Model of Bursting Pancreatic Cells</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 contains partial differentials and as such can not currently be solved by existing CellML tools.</para>
</section>
<sect1 id="sec_structure">
<title>Model Structure</title>
<para>
Through the continuous activity of ion pumps in the plasma membrane, relatively steep transmembrane electrochemical gradients are maintained. Because the transmembrane distributions of many ions such as Na
<superscript>+</superscript>
, K
<superscript>+</superscript>
and Ca
<superscript>2+</superscript>
are far from equilibrium, cells are inclined towards excitable electrical activity, or the membrane potential, determined by relative charge distribution, exhibits complicated patterns of slow and fast oscillations associated with variations in the transmembrane ionic currents. These dynamics play an essential role in intracellular function and intercellular communication.
</para>
<para>
When exposed to a threshold concentration of glucose, pancreatic beta-cells exhibit a complicated pattern of electrical activity. Bursts of action potential spikes (the "active" phase) are observed, separated by a "silent" phase of membrane repolarisation. Insulin secretion is dependent on the relative amount of time the cells spend in the active state, and this time increases with the concentration of extracellular glucose. Bursting dynamics control the influx of Ca
<superscript>2+</superscript>
into the cell, and in turn, Ca
<superscript>2+</superscript>
triggers the release of insulin. So, via this mechanism, the bursting dynamics of the pancreatic beta-cells regulate their response to varying glucose concentrations. Below a threshold glucose concentration (about 5mM), the cells do not burst. Above a certain concentration (> 22 mM), the cells display continuous spiking, and insulin secretion becomes saturated.
</para>
<para>
Mathematical models of pancreatic beta-cells are usually based on the Hodgkin-Huxley formalism (for the original model see
<ulink url="${HTML_EXMPL_HHSA_INTRO}">The Hodgkin-Huxley Squid Axon Model, 1952</ulink>
), with elaborations to account for Ca
<superscript>2+</superscript>
storage, glucose metabolism, and regulation by ATP and various hormones. Several models have been published (see
<ulink url="${HTML_REPOSITORY_INTRODUCTION}">the CellML repository</ulink>
for more pancreatic beta-cell and calcium oscillation models), but although some have been established for some years, their bifurcation structure is so complicated it is not yet fully understood. The goal of the 2001 Mosekilde
<emphasis>et al.</emphasis>
paper analysed here was to give an accurate, but simplified account of the bifurcation structure of the individual beta-cell (see
<xref linkend="fig_cell_diagram" />
below).
</para>
<para>The complete original paper reference is cited below:</para>
<para>
<ulink url="http://www.sciencedirect.com/science?_ob=ArticleURL&_udi=B6T2K-4447MJD-J&_user=140507&_coverDate=12%2F31%2F2001&_alid=70440630&_rdoc=1&_fmt=summary&_orig=search&_qd=1&_cdi=4921&_sort=d&_docanchor=&wchp=dGLbVlz-lSzBk&_acct=C000011498&_version=1&_urlVersion=0&_userid=140507&md5=dc19bf053e438dae9918fa3c279f2f7e">Bifurcation structure of a model of bursting pancreatic cells</ulink>
, Erik Mosekilde, Brian Lading, Sergiy Yanchuk and Yuri Maistrenko, 2001,
<ulink url="http://www.sciencedirect.com/science?_ob=JournalURL&_cdi=4921&_auth=y&_acct=C000011498&_version=1&_urlVersion=0&_userid=140507&md5=511bbadc6ebfd16e10115a252026e228">
<emphasis>Biosystems</emphasis>
</ulink>
, 63, 3-13. (PDF and
<ulink url="http://www.sciencedirect.com/science?_ob=ArticleURL&_udi=B6T2K-4447MJD-J&_coverDate=12%2F31%2F2001&_alid=70440630&_rdoc=1&_fmt=&_orig=search&_qd=1&_cdi=4921&_sort=d&wchp=dGLbVlz-lSzBk&_acct=C000011498&_version=1&_urlVersion=0&_userid=140507&md5=63f03834b470d0be17a65ca137c26f84">full text</ulink>
versions of the article are available to subscribers on the journal website.)
<ulink url="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=11595325&dopt=Abstract">PubMed ID: 11595325</ulink>
</para>
<para>
The raw CellML description of the model can be downloaded in various formats as described in
<xref linkend="sec_download_this_model" />
</para>
<informalfigure float="0" id="fig_cell_diagram">
<mediaobject>
<imageobject>
<objectinfo>
<title>diagram of the model</title>
</objectinfo>
<imagedata fileref="mosekilde_2001.png" />
</imageobject>
</mediaobject>
<caption>
A schematic representation of the ionic currents described by the Mosekilde
<emphasis>et al.</emphasis>
2001 pancreatic beta-cell model. The model includes a calcium current, I
<subscript>
Ca
<superscript>2+</superscript>
</subscript>
; a potassium current, I
<subscript>K</subscript>
; and a slow current, I
<subscript>S</subscript>
.
</caption>
</informalfigure>
</sect1>
</article>
</documentation>
<units name="nanoA_per_cm2">
<unit exponent="-2.0" prefix="centi" units="metre" />
<unit prefix="nano" units="ampere" />
</units>
<units name="per_second">
<unit exponent="-1.0" units="second" />
</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="microS_per_cm2">
<unit exponent="-2.0" prefix="centi" units="metre" />
<unit prefix="micro" units="siemens" />
</units>
<component name="environment">
<variable cmeta:id="environment.time" name="time" public_interface="out" units="second" />
</component>
<component name="membrane">
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<variable cmeta:id="membrane.tau" initial_value="0.02" name="tau" public_interface="out" units="second" />
<variable cmeta:id="membrane.time" name="time" public_interface="in" units="second" />
<variable cmeta:id="membrane.i_K" name="i_K" public_interface="in" units="nanoA_per_cm2" />
<variable cmeta:id="membrane.i_Ca" name="i_Ca" public_interface="in" units="nanoA_per_cm2" />
<variable cmeta:id="membrane.i_S" name="i_S" public_interface="in" units="nanoA_per_cm2" />
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<apply id="membrane_voltage_diff_eq">
<eq />
<apply>
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<variable cmeta:id="calcium_current.V_K" name="V_K" public_interface="in" units="millivolt" />
<variable cmeta:id="calcium_current.m_infinity" name="m_infinity" private_interface="in" units="dimensionless" />
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<ci>V_K</ci>
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<apply>
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<ci>V_K</ci>
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</apply>
</apply>
</apply>
</math>
</component>
<component name="calcium_current_m_gate">
<variable cmeta:id="calcium_current_m_gate.m_infinity" name="m_infinity" public_interface="out" units="dimensionless" />
<variable cmeta:id="calcium_current_m_gate.theta_m" initial_value="12.0" name="theta_m" units="millivolt" />
<variable cmeta:id="calcium_current_m_gate.V_m" initial_value="-20.0" name="V_m" units="millivolt" />
<variable cmeta:id="calcium_current_m_gate.V" name="V" public_interface="in" units="millivolt" />
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<apply>
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<apply>
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<apply>
<exp />
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<variable cmeta:id="potassium_current.J21" name="J21" public_interface="out" private_interface="in" units="dimensionless" />
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<variable cmeta:id="potassium_current.g_K" initial_value="10.0" name="g_K" units="microS_per_cm2" />
<variable cmeta:id="potassium_current.time" name="time" public_interface="in" private_interface="out" units="second" />
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<variable cmeta:id="potassium_current.tau" name="tau" public_interface="in" private_interface="out" units="second" />
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<variable cmeta:id="potassium_current_n_gate.J22" name="J22" public_interface="out" units="dimensionless" />
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<dcterms:description>potassium reversal potential</dcterms:description>
</rdf:Description>
<rdf:Description rdf:about="#calcium_current.V">
<semsim:isComputationalComponentFor>
<rdf:Description rdf:about="#property_7">
<semsim:hasPhysicalDefinition rdf:resource="https://identifiers.org/opb/OPB_00506" />
</rdf:Description>
</semsim:isComputationalComponentFor>
<dcterms:description>membrane potential</dcterms:description>
</rdf:Description>
<rdf:Description rdf:about="#membrane.i_S">
<semsim:isComputationalComponentFor>
<rdf:Description rdf:about="#property_3">
<semsim:hasPhysicalDefinition rdf:resource="https://identifiers.org/opb/OPB_00318" />
</rdf:Description>
</semsim:isComputationalComponentFor>
<dcterms:description>slow current</dcterms:description>
</rdf:Description>
<rdf:Description rdf:about="mosekilde_lading_yanchuk_maistrenko_2001.cellml#membrane.i_K">
<dcterms:description>potassium current</dcterms:description>
</rdf:Description>
<rdf:Description rdf:about="mosekilde_lading_yanchuk_maistrenko_2001.cellml#membrane.time">
<bqbiol:is rdf:resource="https://identifiers.org/opb/OPB_01023" />
</rdf:Description>
<rdf:Description rdf:about="#slow_current.tau">
<dcterms:description>activation time constant of potassium current channel</dcterms:description>
</rdf:Description>
<rdf:Description rdf:about="mosekilde_lading_yanchuk_maistrenko_2001.cellml#calcium_current.i_Ca">
<dcterms:description>calcium current</dcterms:description>
</rdf:Description>
<rdf:Description rdf:about="mosekilde_lading_yanchuk_maistrenko_2001.cellml#membrane.i_S">
<dcterms:description>slow current</dcterms:description>
</rdf:Description>
<rdf:Description rdf:about="#calcium_current.V_K">
<semsim:isComputationalComponentFor>
<rdf:Description rdf:about="#property_8">
<semsim:hasPhysicalDefinition rdf:resource="https://identifiers.org/opb/OPB_00506" />
</rdf:Description>
</semsim:isComputationalComponentFor>
<dcterms:description>potassium reversal potential</dcterms:description>
</rdf:Description>
<rdf:Description rdf:about="mosekilde_lading_yanchuk_maistrenko_2001.cellml#slow_current_S_gate.tau_S">
<dcterms:description>activation time constant of slow current channel</dcterms:description>
</rdf:Description>
<rdf:Description rdf:about="mosekilde_lading_yanchuk_maistrenko_2001.cellml#potassium_current.tau">
<dcterms:description>activation time constant of potassium current channel</dcterms:description>
</rdf:Description>
<rdf:Description rdf:about="#slow_current.tau_S">
<dcterms:description>activation time constant of slow current channel</dcterms:description>
</rdf:Description>
<rdf:Description rdf:about="#potassium_current.V_K">
<semsim:isComputationalComponentFor>
<rdf:Description rdf:about="#property_13">
<semsim:hasPhysicalDefinition rdf:resource="https://identifiers.org/opb/OPB_00506" />
</rdf:Description>
</semsim:isComputationalComponentFor>
<dcterms:description>potassium reversal potential</dcterms:description>
</rdf:Description>
<rdf:Description rdf:about="mosekilde_lading_yanchuk_maistrenko_2001.cellml#calcium_current.time">
<bqbiol:is rdf:resource="https://identifiers.org/opb/OPB_01023" />
</rdf:Description>
<rdf:Description rdf:about="#potassium_current.i_K">
<semsim:isComputationalComponentFor>
<rdf:Description rdf:about="#property_12">
<semsim:hasPhysicalDefinition rdf:resource="https://identifiers.org/opb/OPB_00318" />
</rdf:Description>
</semsim:isComputationalComponentFor>
<dcterms:description>potassium current</dcterms:description>
</rdf:Description>
<rdf:Description rdf:about="mosekilde_lading_yanchuk_maistrenko_2001.cellml#membrane.i_Ca">
<dcterms:description>calcium current</dcterms:description>
</rdf:Description>
</rdf:RDF>
</model>
