Waiting time distributions for clusters of IP3 receptors

Inositol 1,4,5-trisphosphate (IP3R) receptor channels control release of Ca2+ from the endoplasmic reticulum into the cytosol of a cell. The binding of both 1,4,5-trisphosphate (IP3) and activating Ca2+ is required for the channel to open. At high Ca2+ concentrations, IP3Rs are inhibited. IP3Rs are composed of four identical subunits and form in clusters. Many models have been proposed to describe how the binding of IP3 and Ca2+ to subunits results in the opening and closing of IP3Rs. Here we compare the opening and closing probability distributions for clusters of IP3Rs, 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 Ca2+ and IP3 concentrations are varied.