On Conduction in a Bacterial Sodium Channel

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 Ca 2+ 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.