A single-pool inositol 1,4,5-triphosphate-receptor-based model for agonist-stimulated oscillations in Ca 2+ concentration

Model Structure

Ca²⁺ is a ubiquitous intracellular secondary messenger, and evidence from several different cell types suggests that an important mode of signalling is through oscillations rather than the maintenance of a steady state level. The oscillatory behaviour of inositol 1,4,5-triphosphate (IP3)-mediated Ca²⁺ release has been modelled by Gary W. De Young and Joel Keizer. Their 1992 paper is referenced fully below.

A single-pool inositol 1,4,5-triphosphate-receptor-based model for agonist-stimulated oscillations in Ca²⁺ concentration, Gary W. De Young and Joel Keizer, 1992, Proc. Natl. Acad. Sci. USA , 89, 9895-9899. (A PDF of the article is available to subscribers on the PNAS website.) PubMed ID: 1329108

Several mechanisms have been proposed to explain oscillations of intracellular Ca²⁺ concentration in cells. In this study, De Young and Keizer investigate the idea that a biphasic response of the IP3 receptor/channel to cytosolic Ca²⁺ may alone be sufficient to induce Ca²⁺ oscillations.

They constructed a simplified model of the IP3 receptor/channel by assuming that three equivalent and independent subunits are involved in Ca²⁺ conduction. Each subunit has three binding sites: one for IP3, one for Ca²⁺ activation, and one for Ca²⁺ inactivation. Thus each subunit may exist in eight states with transitions governed by second-order (association) and first-order (dissociation) rate constants (see below). All three subunits must be in the state S₁₁₀ (one IP3 and one activating Ca²⁺ bound) for the channel to be open and conducting.

The raw CellML description of the IP3-mediated Ca²⁺ release model can be downloaded in various formats as described in .

A schematic diagram of the kinetics of an IP3 receptor/channel subunit.