Comparison of Models for IP(3) Receptor Kinetics Using Stochastic Simulations

Inositol 1,4,5-trisphosphate receptor (IP(3)R) is a ubiquitous intracellular calcium (Ca(2+)) channel which has a major role in controlling Ca(2+) levels in neurons. A variety of computational models have been developed to describe the kinetic function of IP(3)R under different conditions. In the field of computational neuroscience, it is of great interest to apply the existing models of IP(3)R when modeling local Ca(2+) transients in dendrites or overall Ca(2+) dynamics in large neuronal models. The goal of this study was to evaluate existing IP(3)R models, based on electrophysiological data. This was done in order to be able to suggest suitable models for neuronal modeling. Altogether four models (Othmer and Tang, 1993; Dawson et al., 2003; Fraiman and Dawson, 2004; Doi et al., 2005) were selected for a more detailed comparison. The selection was based on the computational efficiency of the models and the type of experimental data that was used in developing the model. The kinetics of all four models were simulated by stochastic means, using the simulation software STEPS, which implements the Gillespie stochastic simulation algorithm. The results show major differences in the statistical properties of model functionality. Of the four compared models, the one by Fraiman and Dawson (2004) proved most satisfactory in producing the specific features of experimental findings reported in literature. To our knowledge, the present study is the first detailed evaluation of IP(3)R models using stochastic simulation methods, thus providing an important setting for constructing a new, realistic model of IP(3)R channel kinetics for compartmental modeling of neuronal functions. We conclude that the kinetics of IP(3)R with different concentrations of Ca(2+) and IP(3) should be more carefully addressed when new models for IP(3)R are developed.