Multipurpose Na⁺ ions mediate excitation and cellular homeostasis: Evolution of the concept of Na⁺ pumps and Na⁺/Ca²⁺ exchangers

Ionic signalling is the most ancient form of regulation of cellular functions in response to environmental challenges. Signals, mediated by Na⁺ fluxes and spatio-temporal fluctuations of Na⁺ concentration in cellular organelles and cellular compartments contribute to the most fundamental cellular processes such as membrane excitability and energy production. At the very core of ionic signalling lies the Na⁺-K⁺ ATP-driven pump (or NKA) which creates trans-plasmalemmal ion gradients that sustain ionic fluxes through ion channels and numerous Na⁺-dependent transporters that maintain cellular and tissue homeostasis. Here we present a brief account of the history of research into NKA, Na⁺ -dependent transporters and Na⁺ signalling.