Sodium channels need not open before they inactivate

Abstract

Most, if not all, types of voltage-gated channels inactivate. Channels that have been driven open by a depolarization will enter a non-conducting, inactivated state if the depolarization is maintained long enough. This inactivated state is different from the resting closed state because inactivated channels cannot be forced open by depolarization. Opinion about the mechanism of inactivation has ranged from Hodgkin and Huxley's original supposition that the inactivation process proceeds independently of events leading to channel opening^1–3 to the more recent view that a channel normally must open before inactivating^4–5. Intermediate theories suppose that activation processes—but not necessarily the actual opening of channels—are more or less tightly coupled to inactivation^6–9. We now provide evidence, based on recordings of currents flowing through single sodium channels, that channel opening is not a prerequisite for inactivation to occur, and that inactivation seems to proceed independently of activation.