Na+ currents that fail to inactivate

Textbook accounts give the impression that Na+ channels are short-acting binary switches: depolarization opens them, but only for about one millisecond. In contrast to this simplified view, a small but significant fraction of the total Na+ current in neurons occurs because channels open after long delays or in long-duration bursts of openings. Such non-inactivating Na+ current acts physiologically in neurons to amplify synaptic potentials and enhance endogenous rhythmicity, and also to aid repetitive firing of action potentials. In glial cells it also may regulate Na(+)-K+ ATPase activity. The evidence for non-inactivating Na+ current in a variety of neurons and glia is reviewed, along with a brief discussion of its ion channel substrate and its relevance for neurological diseases and drug therapy.