Crosslink of calcium and sodium signalling in health and disease

Abstract

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.

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