Modelling 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 series of discrete transitions that carry one elementary charge for each notch of the screw helix. After the channel has been activated by the first two steps R in equilibrium with P in equilibrium with A in all four domains, followed by a voltage-independent rearrangement, it is opened by a third cooperative step A in equilibrium with B in domains I, II and III in conjunction with hydration. Inactivation is a voltage-dependent process controlled by the third step A in equilibrium with I in sensor IVS4, and the closing of the channel is brought about its dehydration. From the inactivated steady state the channel may be reopened by a fourth step, I in equilibrium with C in sensor IVS4 and rehydration. The computed kinetics of the model are shown to conform closely with those observed experimentally.
Keynes
R D
RD
Physiological Laboratory, University of Cambridge, UK.
Elinder
F
F
D000818:Animals; D006801:Humans; D015640:Ion Channel Gating / Q000502:physiology*; D007473:Ion Channels / Q000502:physiology*; D008954:Models, Biological; D008962:Models, Theoretical
D007473:Ion Channels