Function- and agonist-specific Ca~(2+) signalling: the requirement for and mechanism of spatial and temporal complexity in Ca~(2+) signals

摘要

Calcium signals have been implicated in the regulation of many diverse cellular processes. The problem of how information from extracellular signals is delivered with specificity and fidelity using fluctuations in cytosolic Ca~(2+) concentration remains unresolved. The capacity of cells to generate Ca~(2+) signals of sufficient spatial and temporal complexity is the primary constraint on their ability to effectively encode information through Ca~(2+). Over the past decade, a large body of literature has dealt with some basic features of Ca~(2+)-handling in cells, as well as the multiplicity and functional diversity of intracellular Ca~(2+) stores and extracellular Ca~(2+) influx pathways. In principle, physiologists now have the necessary information to attack the problem of function- and agonist-specificity in Ca~(2+) signal transduction. This review explores the data indicating that Ca~(2+) release from diverse sources, including many types of intracellular stores, generates Ca~(2+) signals with sufficient complexity to regulate the vast number of cellular functions that have been reported as Ca~(2+)-dependent. Some examples where such complexity may relate to neuroendocrine regulation of hormone secretion/synthesis are discussed. We show thatthe functional and spatial heterogeneity of Ca~(2+) stores generates Ca~(2+) signals with sufficient spatiotemporal complexity to simultaneously control multiple Ca~(2+)-dependent cellular functions in neuroendocrine systems.