Voltage‐gated sodium channels at 60: structure, function and pathophysiology

Abstract Voltage‐gated sodium channels initiate action potentials in nerve, muscle and other excitable cells. The sodium current that initiates the nerve action potential was discovered by Hodgkin and Huxley using the voltage clamp technique in their landmark series of papers in The Journal of Physiology in 1952. They described sodium selectivity, voltage‐dependent activation and fast inactivation, and they developed a quantitative model for action potential generation that has endured for many decades. This article gives an overview of the legacy that has evolved from their work, including development of conceptual models of sodium channel function, discovery of the sodium channel protein, analysis of its…