The chemistry of electrical signaling in sodium channels from bacteria and beyond.

Electrical signaling is essential for all fast processes in biology, but its molecular mechanisms have been uncertain. This review article focuses on studies of bacterial sodium channels in order to home in on the essential molecular and chemical mechanisms underlying transmembrane ion conductance and voltage-dependent gating without the overlay of complex protein interactions and regulatory mechanisms in mammalian sodium channels. This minimalist approach has yielded a nearly complete picture of sodium channel function at the atomic level that are mostly conserved in mammalian sodium channels, including sodium selectivity and conductance, voltage sensing and activation, electromechanical coupling to pore opening and closing, slow inactivation, and pathogenic dysfunction in a debilitating channelopathy. Future studies of nature's simplest sodium channels may continue to yield key insights into the fundamental molecular and chemical principles of their function and further elucidate the chemical basis of electrical signaling. [Display omitted] In this review, Catterall et al. describe how electrical signals are generated in excitable cells by voltage-gated sodium channels. The authors highlight fundamental molecular and chemical mechanisms that have arisen in evolution that are crucial to improve our understanding of sodium channel diseases and to develop improved therapies. [ABSTRACT FROM AUTHOR]