Changing perspectives on how the permeation pathway through potassium channels is regulated

The primary means by which ion permeation through potassium channels is controlled, and the key to selective intervention in a range of pathophysiological conditions, is the process by which channels switch between non-conducting and conducting states. Conventionally, this has been explained by a steric mechanism in which the pore alternates between two conformations: a ‘closed’ state in which the conduction pathway is occluded and an ‘open’ state in which the pathway is sufficiently wide to accommodate fully hydrated ions. Recently, however, ‘non-canonical’ mechanisms have been proposed for some classes of K⁺ channels. The purpose of this review is to illuminate structural and dynamic relationships underpinning permeation control in K⁺ channels, indicating where additional data might resolve some of the remaining issues. (Figure presented.).