On conduction in a bacterial sodium channel.

ABSTRACT: Voltage-gated Na?-channels are transmembrane proteins that are responsible for the fast depolarizing phase of the action potential in nerve and muscular cells. Selective permeability of Na? over Ca²? or K? ions is essential for the biological function of Na?-channels. After the emergence of the first high-resolution structure of a Na?-channel, an anionic coordination site was proposed to confer Na? selectivity through partial dehydration of Na? via its direct interaction with conserved glutamate side chains. By combining molecular dynamics simulations and free-energy calculations, a low-energy permeation pathway for Na? ion translocation through the selectivity filter of the recently determined crystal structure of a prokaryotic sodium channel from Arcobacter butzleri is characterised. The picture that emerges is that of a pore preferentially occupied by two ions, which can switch between different configurations by crossing low free-energy barriers. In contrast to K?-channels, the movements of the ions appear to be weakly coupled in Na?-channels. When the free-energy maps for Na? and K? ions are compared, a selective site is characterised in the narrowest region of the filter, where a hydrated Na? ion, and not a hydrated K? ion, is energetically stable.

SUBMITTER: Furini S 

PROVIDER: S-EPMC3320569 | biostudies-literature | 2012

REPOSITORIES: biostudies-literature