Function- and agonist-specific Ca2+signalling: The requirement for and mechanism of spatial and temporal complexity in Ca2+signals

Abstract

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 Ca2+concentration remains unresolved. The capacity of cells to generate Ca2+signals of sufficient spatial and temporal complexity is the primary constraint on their ability to effectively encode information through Ca2+. Over the past decade, a large body of literature has dealt with some basic features of Ca2+-handling in cells, as well as the multiplicity and functional diversity of intracellular Ca2+stores and extracellular Ca2+influx pathways. In principle, physiologists now have the necessary information to attack the problem of function- and agonist-specificity in Ca2+signal transduction. This review explores the data indicating that Ca2+release from diverse sources, including many types of intracellular stores, generates Ca2+signals with sufficient complexity to regulate the vast number of cellular functions that have been reported as Ca2+-dependent. Some examples where such complexity may relate to neuroendocrine regulation of hormone secretion/synthesis are discussed. We show that the functional and spatial heterogeneity of Ca2+stores generates Ca2+signals with sufficient spatiotemporal complexity to simultaneously control multiple Ca2+-dependent cellular functions in neuroendocrine systems.Key words: signal coding, IP3receptor, ryanodine receptor, endoplasmic reticulum, Golgi, secretory granules, mitochondria, exocytosis.