Modeling the intracellular organization of calcium signaling

Abstract

Calcium (Ca²⁺) is a key signaling ion that plays a fundamental role in many cellular processes in most types of tissues and organisms. The versatility of this signaling pathway is remarkable. Depending on the cell type and the stimulus, intracellular Ca²⁺ increases can last over different periods, as short spikes or more sustained signals. From a spatial point of view, they can be localized or invade the whole cell. Such a richness of behaviors is possible thanks to numerous exchange processes with the external medium or internal Ca²⁺ pools, mainly the endoplasmic or sarcoplasmic reticulum and mitochondria. These fluxes are also highly regulated. In order to get an accurate description of the spatiotemporal organization of Ca²⁺ signaling, it is useful to resort to modeling. Thus, each flux can be described by an appropriate kinetic expression. Ca²⁺ dynamics in a given cell type can then be simulated by a modular approach, consisting of the assembly of computational descriptions of the appropriate fluxes and regulations. Modeling can also be used to get insight into the mechanisms of decoding of the Ca²⁺ signals responsible for cellular responses. Cells can use frequency or amplitude coding, as well as take profit of Ca²⁺ oscillations to increase their sensitivity to small average Ca²⁺ increases.