On Conduction and Gating in K+-Channels

Potassium channels can conduct passively K+ ions with rates of up to ∼ 108 ions per second at physiological conditions, and they are selective to these species by a factor of 104 over Na+ ions. Ion conduction has been proposed to involve transitions between two main states, with two or three K+ ions occupying the selectivity filter separated by an intervening water molecule. The largest free energy barrier of such a process was reported to be of the order of 2-3kcal mol−1. Here, we present an alternative mechanism for conduction of K+ in K+ channels where site vacancies are involved, and we propose that coexistence of several ion permeation mechanisms is energetically possible. Conduction can be described as a more anarchic phenomenon than previously characterized by the concerted translocations of K+-water-K+. Experiments also suggest that local structural changes in the selectivity filter may act as the a gate referred to as C-type inactivation. An extensive computational study on KirBac, is presented which supports the existence of a physical gate or constriction in the selectivity filter of K+ channels. Our computations identify a new selectivity filter structure, which is likely associated with C-type inactivation.