Crosslink of calcium and sodium signalling in health and disease

Transmembrane ionic gradients, that are indispensable feature of life, are utilised for generation of cytosolic ionic signals that regulate a host of cellular functions. Intracellular signalling mediated by Ca2+ and Na+ is tightly linked through several molecular pathways that generate Ca2+ and Na+ fluxes and are in turn regulated by both ions. Transient receptor potential (TRP) channels bridge endoplasmic reticulum Ca2+ release with generation of Na+ and Ca2+ currents. Plasmalemmal Na+/Ca2+ exchanger by flickering between forward and reverse mode coordinates influx and efflux of both ions with membrane polarisation and cytosolic ion concentration. The mitochondrial calcium uniporter channel (MCU) and mitochondrial Na+/Ca2+ exchanger, NCLX, mediate Ca2+ entry into and release from this organelle and couple cytosolic Ca2+ and Na+ fluctuations with cellular energetics. Cellular Ca2+ and Na+ signalling controls numerous functional responses and, in the CNS, provides for fast regulation of astroglial homeostatic cascades that are critical for maintenance of synaptic transmission.