Mechanism of ion permeation and selectivity in a voltage gated sodium channel

Abstract

The rapid and selective transport of Na(+) through sodium channels is essential for initiating action potentials within excitable cells. However, an understanding of how these channels discriminate between different ion types and how ions permeate the pore has remained elusive. Using the recently published crystal structure of a prokaryotic sodium channel from Arcobacter butzleri, we are able to determine the steps involved in ion transport and to pinpoint the location and likely mechanism used to discriminate between Na(+) and K(+). Na(+) conduction is shown to involve the loosely coupled "knock-on" movement of two solvated ions. Selectivity arises due to the inability of K(+) to fit between a plane of glutamate residues with the preferred solvation geometry that involves water molecules bridging between the ion and carboxylate groups. These mechanisms are different to those described for K(+) channels, highlighting the importance of developing a separate mechanistic understanding of Na(+) and Ca(2+) channels.