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

• Published in: The Journal of physiology Vol. 599; no. 7; pp. 1961 - 1976
• Main Authors: Black, Katrina A., Jin, Ruitao, He, Sitong, Gulbis, Jacqueline M.
• Format: Journal Article
• Language: English
• Published: England Wiley Subscription Services, Inc 01.04.2021
• Subjects: cryo‐EM; crystal structure; molecular dynamics; non‐canonical gating; permeation gating; Potassium; Potassium - metabolism; potassium channel; Potassium channels; Potassium Channels - metabolism; Protein Conformation; selectivity filter; permeation gating; selectivity filter; crystal structure; non-canonical gating; potassium channel; molecular dynamics; cryo-EM
• ISSN: 0022-3751; 1469-7793
• DOI: 10.1113/JP278682

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 legend Hypothetical mechanisms of control over ion permeation through potassium channels. The upper panel portrays the canonical steric pore‐gating mechanism, while the lower panels depict emerging models. Of these, the left‐hand panel describes the situation in which steric changes have been ruled out and gating has been ascribed to the selectivity filter, whereas the right‐hand panel shows a ‘dewetting’ model, which is neither contingent upon nor excludes steric changes within the pore.