LeBeau, Yule, Groblewski, Sneyd, 1999

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 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.