A model of IP3 receptor with a luminal calcium binding site: stochastic simulations and analysis.

We have constructed a stochastic model of the inositol 1,4,5-trisphosphate receptor-Ca2+ channel that is based on quantitative measurements of the channel's properties. It displays the observed dependence of the open probability of the channel with cytosolic [Ca2+] and [IP3] and gives values for the dwell times that agree with the observations. The model includes an explicit dependence of channel gating with luminal calcium. This not only explains several observations reported in the literature, but also provides a possible explanation of why the open probabilities and shapes of the bell-shaped curves reported in [Nature 351 (1991) 751] and in [Proc. Natl. Acad. Sci. U.S.A. 269 (1998) 7238] are so different.