Na+ channels play a crucial role in generating action potentials in neurones and other excitable cells. alpha-subunits, composed of four homologous repeats, are responsible for most of the Na+ channel properties. The combination of molecular biology with electro-physiological tools has proved useful for understanding the molecular mechanism of the channel function. Activation, inactivation and ion permeation occur, based on Segment 4, III-IV linker, the region intervened by Segment 5 and 6, respectively. Mutations in a human skeletal muscle Na+ channel gene cause heritable muscle disorders, hyperkalemic periodic paralysis and paramyotonica congenita. Future directions in Na+ channel studies may include gene regulation of the Na+ channel related to neural cell fate and subcellular localization of channel molecules concurrent with plasticity or development.