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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.

SUBMITTER: Vora T

PROVIDER: S-EPMC2483743 | biostudies-literature | 2008 Aug

REPOSITORIES: biostudies-literature

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Conduction of Na+ and K+ through the NaK channel: molecular and Brownian dynamics studies.

Vora Taira T Bisset David D Chung Shin-Ho SH

Biophysical journal 20080502 4

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 i ...[more]

PMID: 18456826

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Project description:Identification of the molecular interaction governing ion conduction through biological pores is one of the most important goals of modern electrophysiology. Grand canonical Monte Carlo Brownian dynamics (GCMC/BD) and three-dimensional Poisson-Nernst-Plank (3d-PNP) electrodiffusion algorithms offer powerful and general approaches to study of ion permeation through wide molecular pores. A detailed analysis of ion flows through the staphylococcal alpha-hemolysin channel based on series of simulations at different concentrations and transmembrane potentials is presented. The position-dependent diffusion coefficient is approximated on the basis of a hydrodynamic model. The channel conductance calculated by GCMC/BD is approximately 10% higher than (electrophysiologically measured) experimental values, whereas results from 3d-PNP are always 30-50% larger. Both methods are able to capture all important electrostatic interactions in equilibrium conditions. The asymmetric conductance upon the polarity of the transmembrane potential observed experimentally is reproduced by GCMC/BD and 3d-PNP. The separation of geometrical and energetic influence of the channel on ion conduction reveals that such asymmetries arise from the permanent charge distribution inside the pore. The major determinant of the asymmetry is unbalanced charge in the triad of polar residues D127, D128, and K131. The GCMC/BD or 3d-PNP calculations reproduce also experimental reversal potentials and permeability rations in asymmetric ionic solutions. The weak anionic selectivity of the channel results from the presence of the salt bridge between E111 and K147 in the constriction zone. The calculations also reproduce the experimentally derived dependence of the reversible potential to the direction of the salt gradient. The origin of such effect arises from the asymmetrical distribution of energetic barriers along the channel axis, which modulates the preferential ion passage in different directions.

Dataset Information

Conduction of Na+ and K+ through the NaK channel: molecular and Brownian dynamics studies.

Publications

Conduction of Na+ and K+ through the NaK channel: molecular and Brownian dynamics studies.

Similar Datasets

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