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Biophys J. 2013 Jun 4;104(11):2401-9. doi: 10.1016/j.bpj.2013.04.035.

The mechanism of Na⁺/K⁺ selectivity in mammalian voltage-gated sodium channels based on molecular dynamics simulation.

Author information

  • 1MOE Key Laboratory of Bioinformatics, School of Life Sciences, Tsinghua University, Beijing, China.

Abstract

Voltage-gated sodium (Nav) channels and their Na⁺/K⁺ selectivity are of great importance in the mammalian neuronal signaling. According to mutational analysis, the Na⁺/K⁺ selectivity in mammalian Nav channels is mainly determined by the Lys and Asp/Glu residues located at the constriction site within the selectivity filter. Despite successful molecular dynamics simulations conducted on the prokaryotic Nav channels, the lack of Lys at the constriction site of prokaryotic Nav channels limits how much can be learned about the Na⁺/K⁺ selectivity in mammalian Nav channels. In this work, we modeled the mammalian Nav channel by mutating the key residues at the constriction site in a prokaryotic Nav channel (NavRh) to its mammalian counterpart. By simulating the mutant structure, we found that the Na⁺ preference in mammalian Nav channels is collaboratively achieved by the deselection from Lys and the selection from Asp/Glu within the constriction site.

Copyright © 2013 Biophysical Society. Published by Elsevier Inc. All rights reserved.

PMID:
23746512
[PubMed - indexed for MEDLINE]
PMCID:
PMC3672897
Free PMC Article
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