title: 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.
authors.affiliation: Physical and Theoretical Chemistry Laboratory, Department of Chemistry, University of Oxford, Oxford, United Kingdom.
authors.forename: Simone
authors.initials: S
authors.lastname: Furini
authors.forename: Carmen
authors.initials: C
authors.lastname: Domene
mesh_terms: D001426:Bacterial Proteins / Q000737:chemistry* / Q000648:ultrastructure*; D003198:Computer Simulation; D004553:Electric Conductivity; D015640:Ion Channel Gating; D008956:Models, Chemical; D008958:Models, Molecular; D011487:Protein Conformation; D012964:Sodium / Q000737:chemistry*; D015222:Sodium Channels / Q000737:chemistry* / Q000648:ultrastructure*
chemical_list: D001426:Bacterial Proteins; D015222:Sodium Channels; D012964:Sodium