Agonist-Dependent Phosphorylation Of The Inositol 1,4,5-Triphosphate Receptor
Catherine
Lloyd
Bioengineering Institute, University of Auckland
Model Structure
The production of the intracellular signalling factor inositol 1,4,5-triphosphate (IP3) and the subsequent release of Ca2+ stored in intracellular organelles is a fundamental cellular signalling function. The inositol triphosphate receptor (IPR) is an IP3-activated Ca2+ channel in the ER. The properties of IP3-dependent intracellular calcium oscillations in pancreatic acinar cells depend on the agonist used to stimulate them.
This agonist-dependency is captured in Andrew P. LeBeau et al's 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 below). IP3 must be bound to all four subunits for the receptor to be in the conducting state.
The complete original paper reference is cited below:
Agonist-dependent Phosphorylation of the Inositol 1,4,5-Triphosphate Receptor. A Possible Mechanism for Agonist-specific Calcium Oscillations in Pancreatic Acinar Cells, Andrew P. LeBeau, David I. Yule, Guy E. Groblewski and James Sneyd, 1999,
The Journal Of General Physiology
, 113, 851-871. (Full text and PDF versions of the article are available to subscribers of the JGP website.) PubMed ID: 10352035
The raw CellML description of the dynamic model of the type-2 inositol triphosphate receptor can be downloaded in various formats as described in .
A simplified diagram of the IPR model
A diagram of the receptor states of the model of the IP3 receptor. S denotes the fraction of the subunits in the shut state. Binding of IP3 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 I1 (inactivated) state in which IP3 is still bound but the channels do not conduct. I2 represents a second inactivated state of the receptor in which IP3 is no longer bound.
calcium dynamics
ip3r
Pancreatic Acinar Cell
signal transduction
The University of Auckland
The Bioengineering Institute
Andrew
LeBeau
P
fraction of receptor subunits in the open state
O
fraction of receptor subunits in the inactivated (2) state
I2
Catherine
Lloyd
May
Guy
Groblewski
E
The University of Auckland, Bioengineering Institute
intracellular calcium ion concentration
c
keyword
This is the CellML description of LeBeau et al's 1999 model for
agonist-specific calcium oscillations in pancreatic acinar cells.
10352035
2007-06-05T09:39:09+12:00
Catherine Lloyd
Journal of General Physiology
David
Yule
I
1999-06-01
Agonist-dependent Phosphorylation of the Inositol 1,4,5-Triphosphate Receptor
113
851
871
The new version of this model has been re-coded to remove the reaction element and replace it with a simple MathML description of the model reaction kinetics. This is thought to be truer to the original publication, and information regarding the enzyme kinetics etc will later be added to the metadata through use of an ontology.
The model runs in the PCEnv simulator and gives a nice curved output.
c.lloyd@auckland.ac.nz
James
Sneyd
The LeBeau et al 1999 model for agaonist-specific calcium oscillations
in pancreatic acinar cells.
Pancreatic Acinar Cell
fraction of receptor subunits in the inactivated (1) state
I1
2007-05-21
Catherine
Lloyd
May