Spatiotemporal organization of Ca dynamics: a modeling-based approach.

Calcium is a ubiquitous second messenger that mediates vital physiological responses such as fertilization, secretion, gene expression, or apoptosis. Given this variety of processes mediated by Ca(2+), these signals are highly organized both in time and space to ensure reliability and specificity. This review deals with the spatiotemporal organization of the Ca(2+) signaling pathway in electrically nonexcitable cells in which InsP(3) receptors are by far the most important Ca(2+) channels. We focus on the aspects of this highly regulated dynamical system for which an interplay between experiments and modeling is particularly fruitful. In particular, the importance of the relative densities of the different InsP(3) receptor subtypes will be discussed on the basis of a modeling approach linking the steady-state behaviors of these channels in electrophysiological experiments with their behavior in a cellular environment. Also, the interplay between InsP(3) metabolism and Ca(2+) oscillations will be considered. Finally, we discuss the relationships between stochastic openings of the Ca(2+) releasing channels at the microscopic level and the coordinated, regular behavior observed at the whole cell level on the basis of a combined experimental and modeling approach.