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Potassium channels play critical roles in many physiological processes,providing a selective permeation route for K+ ions in and out of a cell, byemploying a carefully designed selectivity filter, evolutionarily conservedfrom viruses to mammals. The structure of the selectivity filter was determinedat atomic resolution by x-ray crystallography, showing a tight coordination ofdesolvated K+ ions by the channel. However, the molecular mechanism of K+ ionspermeation through potassium channels remains unclear, with structural,functional and computational studies often providing conflicting data andinterpretations. In this review, we will present the proposed mechanisms,discuss their origins, and will critically assess them against all availabledata. General properties shared by all potassium channels are introduced first,followed by the introduction of two main mechanisms of ion permeation: soft anddirect knock-on. Then, we will discuss critical computational and experimentalstudies that shaped the field. We will especially focus on molecular dynamics(MD) simulations, that provided mechanistic and energetic aspects of K+permeation, but at the same time created long-standing controversies. Furtherchallenges and possible solutions are presented as well.

The persistent question of potassium channel permeation mechanisms