- Author:
- neilstephen2001 <npar276@aucklanduni.ac.nz>
- Date:
- 2021-01-25 18:50:11+13:00
- Desc:
- adding OMEX archives to workspace
- Permanent Source URI:
- http://models.cellml.org/workspace/7f1/rawfile/c5079f12eb1d8c164a111eea8277d5627c24a0b2/lebeau_yule_groblewski_sneyd_1999/model/lebeau_yule_groblewski_sneyd_1999.rdf
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<article>
<articleinfo>
<title>Agonist-Dependent Phosphorylation Of The Inositol 1,4,5-Triphosphate Receptor</title>
<author>
<firstname>Catherine</firstname>
<surname>Lloyd</surname>
<affiliation>
<shortaffil>Bioengineering Institute, University of Auckland</shortaffil>
</affiliation>
</author>
</articleinfo>
<sect1 id="sec_structure">
<title>Model Structure</title>
<para>
The production of the intracellular signalling factor inositol 1,4,5-triphosphate (IP
<subscript>3</subscript>
) and the subsequent release of Ca
<superscript>2+</superscript>
stored in intracellular organelles is a fundamental cellular signalling function. The inositol triphosphate receptor (IPR) is an IP
<subscript>3</subscript>
-activated Ca
<superscript>2+</superscript>
channel in the ER. The properties of IP
<subscript>3</subscript>
-dependent intracellular calcium oscillations in pancreatic acinar cells depend on the agonist used to stimulate them.
</para>
<para>
This agonist-dependency is captured in Andrew P. LeBeau
<emphasis>et al's</emphasis>
1999 mathematical model of agonist-specific intracellular calcium oscillations in pancreatic acinar cells. They assume that the complete IPR is composed of four functionally identical, independent subunits, (see
<xref linkend="fig_simplified_diagram" />
below). IP
<subscript>3</subscript>
must be bound to all four subunits for the receptor to be in the conducting state.
</para>
<para>The complete original paper reference is cited below:</para>
<para>
<ulink url="http://www.jgp.org/cgi/content/abstract/113/6/851">Agonist-dependent Phosphorylation of the Inositol 1,4,5-Triphosphate Receptor. A Possible Mechanism for Agonist-specific Calcium Oscillations in Pancreatic Acinar Cells</ulink>
, Andrew P. LeBeau, David I. Yule, Guy E. Groblewski and James Sneyd, 1999,
<ulink url="http://www.jgp.org/">
<emphasis>The Journal Of General Physiology</emphasis>
</ulink>
, 113, 851-871. (
<ulink url="http://www.jgp.org/cgi/content/full/113/6/851">Full text</ulink>
and
<ulink url="http://www.jgp.org/cgi/reprint/113/6/851.pdf">PDF</ulink>
versions of the article are available to subscribers of the JGP website.)
<ulink url="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&amp;db=PubMed&amp;list_uids=10352035&amp;dopt=Abstract">PubMed ID: 10352035</ulink>
</para>
<para>
The raw CellML description of the dynamic model of the type-2 inositol triphosphate receptor can be downloaded in various formats as described in
<xref linkend="sec_download_this_model" />
.
</para>
<informalfigure float="0" id="fig_simplified_diagram">
<mediaobject>
<imageobject>
<objectinfo>
<title>A simplified diagram of the IPR model</title>
</objectinfo>
<imagedata fileref="lebeau_1999.png" />
</imageobject>
</mediaobject>
<caption>
A diagram of the receptor states of the model of the IP
<subscript>3</subscript>
receptor. S denotes the fraction of the subunits in the shut state. Binding of IP
<subscript>3</subscript>
causes the receptor to be converted to the open state O. O is a relatively unstable state and the subunits will progress through to the more stable I
<subscript>1</subscript>
(inactivated) state in which IP
<subscript>3</subscript>
is still bound but the channels do not conduct. I
<subscript>2</subscript>
represents a second inactivated state of the receptor in which IP
<subscript>3</subscript>
is no longer bound.
</caption>
</informalfigure>
</sect1>
</article>
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<semsim:unknown>The LeBeau et al 1999 model for agaonist-specific calcium oscillations
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<semsim:unknown>Pancreatic Acinar Cell</semsim:unknown>
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