title: Conduction of Na+ and K+ through the NaK channel: molecular and Brownian dynamics studies.
abstract: Conduction of ions through the NaK channel, with M0 helix removed, was studied using both Brownian dynamics and molecular dynamics. Brownian dynamics simulations predict that the truncated NaK has approximately a third of the conductance of the related KcsA K+ channel, is outwardly rectifying, and has a Michaelis-Menten current-concentration relationship. Current magnitude increases when the glutamine residue located near the intracellular gate is replaced with a glutamate residue. The channel is blocked by extracellular Ca2+. Molecular dynamics simulations show that, under the influence of a strong applied potential, both Na+ and K+ move across the selectivity filter, although conduction rates for Na+ ions are somewhat lower. The mechanism of conduction of Na+ differs significantly from that of K+ in that Na+ is preferentially coordinated by single planes of pore-lining carbonyl oxygens, instead of two planes as in the usual K+ binding sites. The water-containing filter pocket resulting from a single change in the selectivity filter sequence (compared to potassium channels) disrupts several of the planes of carbonyl oxygens, and thus reduces the filter's ability to discriminate against sodium.
authors.affiliation: Research School of Biological Sciences, Australian National University, Canberra, Australia.
authors.forename: Taira
authors.initials: T
authors.lastname: Vora
authors.forename: David
authors.initials: D
authors.lastname: Bisset
authors.forename: Shin-Ho
authors.initials: SH
authors.lastname: Chung
mesh_terms: D003198:Computer Simulation; D004058:Diffusion; D015640:Ion Channel Gating; D008956:Models, Chemical; D008958:Models, Molecular; D011188:Potassium / Q000737:chemistry*; D012964:Sodium / Q000737:chemistry*; D000254:Sodium-Potassium-Exchanging ATPase / Q000737:chemistry* / Q000648:ultrastructure*
chemical_list: D012964:Sodium; D000254:Sodium-Potassium-Exchanging ATPase; D011188:Potassium