Mitochondrial and ER Calcium Uptake and Release Fluxes and their Interplay in Intact Nerve Cells

Abstract

Ionized free Ca ( Ca ²⁺) is a ubiquitous signaling ion that serves as the critical link between a variety of physiological stimuli and their intracellular effectors. Previous studies of reduced in vitro preparations have provided functional characterizations of various Ca ²⁺ channels, pumps and exchangers that regulate cellular Ca ²⁺ movements. However, little is known about the functional interplay between transporters that are expressed together in intact cells and orchestrate stimulus-evoked changes in [ Ca ²⁺]. This review summarizes recent progress in characterizing Ca ²⁺ transporters in sympathetic neurons, which provide an ideal model for studying Ca ²⁺ dynamics in neurons. Our results show how the functional interplay between Ca ²⁺ transport systems that are regulated by Ca ²⁺ in quantitatively differ-ent ways leads to emergent properties of Ca ²⁺ signaling that are expected to play a critical role in defining how Ca ²⁺ serves its role as a signaling ion.