4.6 Review

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

Journal

JOURNAL OF PHYSIOLOGY-LONDON
Volume 599, Issue 7, Pages 1961-1976

Publisher

WILEY
DOI: 10.1113/JP278682

Keywords

cryo-EM; crystal structure; molecular dynamics; non-canonical gating; permeation gating; potassium channel; selectivity filter

Funding

  1. Walter and Eliza Hall Institute
  2. La Trobe University Postgraduate Research Scholarships

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The primary means for controlling ion permeation through potassium channels is the switching between non-conducting and conducting states. While traditionally explained by a steric mechanism, some classes of K+ channels may have 'non-canonical' mechanisms. The review aims to illuminate the structural and dynamic relationships underlying permeation control in K+ channels.
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.

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