Abstract
NEW FINDINGS: What is the topic of this review? This paper overviews the links between Ca(2+) 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(2+) dynamics. In particular, the narrative focuses on the molecular physiology of plasmalemmal and mitochondrial Na(+) -Ca(2+) exchangers and plasmalemmal transient receptor potential channels. Functional consequences of Ca(2+) 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(2+) and Na(+) is tightly linked through several molecular pathways that generate Ca(2+) and Na(+) fluxes and are in turn regulated by both ions. Transient receptor potential (TRP) channels bridge endoplasmic reticulum Ca(2+) release with generation of Na(+) and Ca(2+) currents. The plasmalemmal Na(+) -Ca(2+) 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(2+) exchanger (NCLX) mediate Ca(2+) entry into and release from this organelle and couple cytosolic Ca(2+) and Na(+) fluctuations with cellular energetics. Cellular Ca(2+) 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.