Figure 8. Quasi-sequential activation model for sodium channel gating.

A simple model depicting the preferential sequence of events during sodium channel activation. The closed to open transition represents all of the steps from resting to activated, and the S2 state represents a distinct conformation of the open pore, which precedes inactivation. In wild-type channels, inactivation occurs sufficiently rapidly from the S2 state so that it is rarely observed. For simplicity, the S1 subconductance is not included here, but this conductance may potentially be represented as a parallel set of states to indicate an independent allosteric conformation of the channel. In this model, inactivation from closed states proceeds via a transition from closed to S2.