Temporal and spatial heterogeneities of Ca2+ signaling: mechanisms and physiological roles

In the cells of the gastrointestinal tract, as in most other types of cells, many of the fundamental cellular functions are mediated by increases of intracellular Ca2+. These increases are mediated primarily by elevations of inositol 1,4,5-trisphosphate (IP3), which, in turn, are a consequence of the activation of specific plasma membrane receptors. Extensive investigations of these intracellular processes in the last few years have revealed the complexities of Ca2+ signaling. The extreme heterogeneity of Ca2+ signaling, which is manifest by variations in both the time course and the spatial distribution of these signals, forms the central theme of this review. On the basis of the available information, the various intracellular mechanisms that allow the manifestation of this heterogeneity are discussed. It is argued that these variations in Ca2+ response are the result not only of the existence of multiple, complex mechanisms participating in the generation and maintenance of the agonist-evoked Ca2+ signal but also of the existence of various isoforms for almost every one of the main molecules involved in signaling and the concomitant participation of many intracellular modulators.