Crosslink between calcium and sodium signalling.

New Findings: What is the topic of this review? This paper overviews the links between Ca and Na signalling in various types of cells. What advances does it highlight? This paper highlights the general importance of ionic signalling and overviews the molecular mechanisms linking Na and Ca dynamics. In particular, the narrative focuses on the molecular physiology of plasmalemmal and mitochondrial Na -Ca exchangers and plasmalemmal transient receptor potential channels. Functional consequences of Ca and Na signalling for co-ordination of neuronal activity with astroglial homeostatic pathways fundamental for synaptic transmission are discussed.

Abstract: Transmembrane ionic gradients, which are an indispensable feature of life, are used for generation of cytosolic ionic signals that regulate a host of cellular functions. Intracellular signalling mediated by Ca and Na is tightly linked through several molecular pathways that generate Ca and Na fluxes and are in turn regulated by both ions. Transient receptor potential (TRP) channels bridge endoplasmic reticulum Ca release with generation of Na and Ca currents. The plasmalemmal Na -Ca exchanger (NCX) flickers between forward and reverse mode to co-ordinate the influx and efflux of both ions with membrane polarization and cytosolic ion concentrations. The mitochondrial calcium uniporter channel (MCU) and mitochondrial Na -Ca exchanger (NCLX) mediate Ca entry into and release from this organelle and couple cytosolic Ca and Na fluctuations with cellular energetics. Cellular Ca and Na signalling controls numerous functional responses and, in the CNS, provides for fast regulation of astroglial homeostatic cascades that are crucial for maintenance of synaptic transmission.