On Conduction and Permeation in a Bacterial Sodium Channel

Carmen Domene Nunez, Simone Furini

Research output: Contribution to journalArticle

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. They are essential for the rapid depolarization of nerve and muscle1, and are important drug targets2. Selective permeability of Na+ over Ca2+ or K+ ions is essential for their biological function. An understanding of how these channels discriminate between different ion types and how ions permeate the pore is not well understood yet. The X-ray structure of the bacterial sodium channel NavAb has provided a new template for the study of sodium. An anionic coordination site was proposed to confer Na+ selectivity through partial dehydration of Na+ via its direct interaction with conserved glutamate side chains. Starting from the crystal structure and by combining molecular dynamics simulations and free-energy calculations a low-energy permeation pathway for Na+ ion translocation through the selectivity filter NavAb 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 energy-barriers. In contrast to K+-channels, the movements of the ions appear to be weakly coupled in Na+-channels. When the 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.
Original languageEnglish
Article number692-Pos B461
Pages (from-to)135A-135A
Number of pages1
JournalBiophysical Journal
Volume104
Issue number2, Supplement 1
DOIs
Publication statusPublished - 29 Jan 2013

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