| Summary: | The three tetrameric voltage-gated K+, Na+, and Ca2+ ion channels share a high number of common structural features. Moreover, they share a common charge distribution over the corresponding molecular components. These common features point to an energetically favored pathway of channel opening. This pathway starts from an ion channel conformation consisting of the activation gate closed and the inactivation gate (i.e., the selectivity filter) open. As a consequence of a depolarizing pulse, the stepwise outward movement of the four S4 helices triggers a series of interlinked electrostatic attractive interactions leading to complete opening of the ion channels. The assumption of a stepwise outward movement of the S4 helices is supported not only by the possibility of accounting for the salient kinetic features of these ion channels with a minimum of two, or at most three, free parameters, but also by a similar experimental stepwise movement of the gating charge.
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