A dynamic model of the type-2 inositol triphosphate receptor

Model Status

This CellML model runs in OpenCell and COR and the units are consistent throughout. The model runs to recreate published results and is currently configured to recreate Figure 4 (Lower Plot, Trace 4), but variation of the IP3 and Calcium concentrations will allow the model to recreate different figures.

Model Structure

ABSTRACT: The dynamic properties of the inositol (1,4,5)-trisphosphate (IP(3)) receptor are crucial for the control of intracellular Ca(2+), including the generation of Ca(2+) oscillations and waves. However, many models of this receptor do not agree with recent experimental data on the dynamic responses of the receptor. We construct a model of the IP(3) receptor and fit the model to dynamic and steady-state experimental data from type-2 IP(3) receptors. Our results indicate that, (i) Ca(2+) binds to the receptor using saturating, not mass-action, kinetics; (ii) Ca(2+) decreases the rate of IP(3) binding while simultaneously increasing the steady-state sensitivity of the receptor to IP(3); (iii) the rate of Ca(2+)-induced receptor activation increases with Ca(2+) and is faster than Ca(2+)-induced receptor inactivation; and (iv) IP(3) receptors are sequentially activated and inactivated by Ca(2+) even when IP(3) is bound. Our results emphasize that measurement of steady-state properties alone is insufficient to characterize the functional properties of the receptor.

The original paper reference is cited below:

A dynamic model of the type-2 inositol triphosphate receptor, James Sneyd and Jean-Francois Dufour, 2002, Proceedings of the National Academy of Sciences , 99, 2398-2403. PubMed ID: 11842185

A simplified diagram of the IPR model, where R represents the free receptor, O is the open state of the channel, A is the activated state of the channel and I1, I2, and S are three inactive states.