Abstract
The mechanism underlying ion permeation through potassium channels still remains controversial. K(+) ions permeate across a narrow selectivity filter (SF) in a single file. Conventional scenarios assume that K(+) ions are tightly bound in the SF, and, thus, they are displaced from their energy well by ion-ion repulsion with an incoming ion. This tight coupling between entering and exiting ions has been called the "knock-on" mechanism. However, this paradigm is contradicted by experimental data measuring the water-ion flux coupling ratio, demonstrating fewer ion occupancies. Here, the results of molecular dynamics simulations of permeation through the KcsA potassium channel revealed an alternative mechanism. In the aligned ions in the SF (an ion queue), the outermost K(+) was readily and spontaneously released toward the extracellular space, and the affinity of the relevant ion was ~ 50 mM. Based on this low-affinity regime, a simple queueing mechanism described by loose coupling of entering and exiting ions is proposed.