Conduction of Na+ and K+ through the NaK Channel: Molecular and Brownian Dynamics Studies

¹ Australian National University

^* To whom correspondence should be addressed. E-mail: shin-ho.chung{at}anu.edu.au.

Submitted on November 27, 2007
Revised on February 14, 2008
Accepted on 16 April 2008

	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 about 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.

Key Words: Brownian dynamics, Channel model, Conductance, Ion permeation, Molecular dynamics, NaK channel