Waiting time distributions for clusters of IP3 receptors.

Inositol 1,4,5-trisphosphate (IP(3)R) receptor channels control release of Ca(2+) from the endoplasmic reticulum into the cytosol of a cell. The binding of both 1,4,5-trisphosphate (IP(3)) and activating Ca(2+) is required for the channel to open. At high Ca(2+) concentrations, IP(3)Rs are inhibited. IP(3)Rs are composed of four identical subunits and form in clusters. Many models have been proposed to describe how the binding of IP(3) and Ca(2+) to subunits results in the opening and closing of IP(3)Rs. Here we compare the opening and closing probability distributions for clusters of IP(3)Rs, resulting from three different models. The distributions are calculated both analytically, using a method we have developed, and with simulations. We found significant differences in the behavior of the three models as the Ca(2+) and IP(3) concentrations are varied.