Mitochondria as regulators of stimulus-evoked calcium signals in neurons

An important challenge in the study of Ca2+ signalling is to understand the dynamics of intracellular Ca2+ levels during and after physiological stimulation. While extensive information is available regarding the structural and biophysical properties of Ca2+ channels, pumps and exchangers that control cellular Ca2+ movements, little is known about the quantitative properties of the transporters that are expressed together in intact cells or about the way they operate as a system to orchestrate stimulus-induced Ca2+ signals. This lack of information is particularly striking given that many qualitative properties of Ca2+ signals (e.g. whether the Ca2+ concentration within a particular organelle rises or falls during stimulation) depend critically on quantitative properties of the underlying Ca2+ transporters (e.g. the rates of Ca2+ uptake and release by the organelle). This monograph describes the in situ characterization of Ca2+ transport pathways in sympathetic neurons, showing how mitochondrial Ca2+ uptake and release systems define the direction and rate of net Ca2+ transport by this organelle, and how the interplay between mitochondrial Ca2+ transport and Ca+2 transport across the plasma membrane contribute to depolarization-evoked Ca2+ signals in intact cells.