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, 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 IP3 and Ca2+ 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 Ca2+ and IP3 concentrations are varied. (C) 2009 Elsevier Ltd. All rights reserved.