Sodium-activated K+ channels (IK(Na)) are a class of large-conductance ion channels expressed in several populations of vertebrate neurons, mammalian cardiac myocytes and Xenopus oocytes. These channels are activated by the binding of Na+ to sites located on the cytoplasmic face of the channel. The physiological functions of IK(Na) channels have been difficult to ascertain, in part because their activation typically requires Na+ concentrations considerably higher than those that are normally present in the cytosol. However, there is now evidence suggesting that IK(Na) can play a role in the regulation of neuronal excitability, the modulation of the action-potential waveform, and the responses of excitable cells to hypoxia and ischemia.