MODELING THE ACTIVATION, OPENING, INACTIVATION AND REOPENING OF THE VOLTAGE-GATED SODIUM-CHANNEL

A model of the voltage-gated sodium channel is put forward suggesting that the four S4 voltage-sensors behave as screw-helices making a seri es of discrete transitions that carry one elementary charge for each n otch of the screw helix. After the channel has been activated by the f irst two steps R reversible arrow P reversible arrow A in all four dom ains, followed by a voltage-independent rearrangement, it is opened by a third cooperative step A reversible arrow B in domains I, II and II I in conjunction with hydration. Inactivation is a voltage-dependent p rocess controlled by the third step A reversible arrow I in sensor IVS 4, and the closing of the channel is brought about its dehydration. Fr om the inactivated steady state the channel may be reopened by a fourt h step, I reversible arrow C in sensor IVS4 and rehydration. The compu ted kinetics of the model are shown to conform closely with those obse rved experimentally.