Modelling the activation, opening, inactivation and reopening of the voltage-gated sodium channel

Proceedings. Biological Sciences
R D Keynes, F Elinder

Abstract

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.

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Citations

Apr 22, 2008·Pflügers Archiv : European journal of physiology·Tobias HuthUlf-Peter Hansen
Nov 8, 2008·Cell Biochemistry and Biophysics·Sara I Börjesson, Fredrik Elinder
Apr 28, 2012·Proceedings of the National Academy of Sciences of the United States of America·Ulrike HenrionFredrik Elinder
Jun 1, 2011·The Journal of General Physiology·Sara I Börjesson, Fredrik Elinder
Apr 2, 1998·Proceedings. Biological Sciences·R D Keynes, F Elinder
May 27, 1999·Proceedings. Biological Sciences·R D Keynes, F Elinder
Jan 15, 2014·The Journal of General Physiology·Nina E OttossonFredrik Elinder
May 27, 2008·Biophysical Journal·Sara I BörjessonFredrik Elinder
Aug 25, 2017·Channels·Kathryn E MangoldJonathan R Silva
Jul 13, 2004·Physical Review. E, Statistical, Nonlinear, and Soft Matter Physics·R P JoshiS J Beebe
Mar 9, 2021·The Journal of General Physiology·Malin Silverå EjnebyLucie Delemotte

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