A comparison of three models of the inositol trisphosphate receptor

Abstract

The inositol (1,4,5)-trisphosphate receptor (IPR) plays a crucial role in calcium dynamics in a wide range of cell types, and is often a central feature in quantitative models of calcium oscillations and waves. We compare three mathematical models of the IPR, fitting each of them to the same data set to determine ranges for the parameter values. Each of the fits indicates that fast activation of the receptor, followed by slow inactivation, is an important feature of the model, and also that the speed of inositol trisphosphate IP3 binding cannot necessarily be assumed to be faster than Ca2+ activation. In addition, the model which assumed saturating binding rates of Ca2+ to the IPR demonstrated the best fit. However, lack of convergence in the fitting procedure indicates that responses to step increases of Ca2+ and IP3 provide insufficient data to determine the parameters unambiguously in any of the models.