Science Topics – 110

Critical roles of the nanocavity of the K+ channel for ion permeation
Takashi Sumikama (Shigetoshi Oiki)

K+ channels are ubiquitous in all types of cells, and in excitable cells, K+ channels regulate the action potential. The mechanism of ion permeation through K+ channels has been studied extensively. For K+ permeation through the channel, there are two parts: one is the selectivity filter (SF), the narrowest part of the channel, and the other is nanocavity (NC), the nanometer-sized entryway from the intracellular solution to the SF. The previous studies have concentrated on the coupling of an ion entrance to the SF and the simultaneous exit of the other ion from the SF (the knock-on mechanism). Also, the NC has been assumed to be an extension of the bulk solution holding multiple ions in it. Here, we studied the ion permeation mechanism through the Kv1.2 channel using the molecular dynamics simulations and found the following unprecedented results. The NC was occupied by one ion at most, and it is mostly vacant. This is originated from the fact that the NC is a nanometer-sized tiny space, in which the concentration is not a continuous quantity, but is a discretized number of ions in a certain space. Moreover, we found that the entry of an ion into the NC initiated the movement of ions in the SF. The nanocavities are often seen in other channel proteins. This study clarified the importance of the NC for ion permeation through channels.

Sumikama T, Oiki S. Digitalized K+ Occupancy in the Nanocavity Holds and Releases Queues of K+ in a Channel. J. Am. Chem. Soc. 138: 10284-10292, 2016.

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Ion permeation through the Kv1.2 channel. There exist two K+ ions in the selectivity filter (blue and green balls). This movie shows that the nanocavity is empty until the arrival of the next permeating ion (red ball) at the nanocavity.

Faculty of Medical Sciences, University of Fukui, Japan