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

Mengdie Xia, Huihui Liu, Yang Li, Nieng Yan, Haipeng Gong

Research output: Contribution to journalArticle

26 Scopus citations

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 Na v 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.

Original languageEnglish (US)
Pages (from-to)2401-2409
Number of pages9
JournalBiophysical Journal
Volume104
Issue number11
DOIs
StatePublished - Jun 4 2013

All Science Journal Classification (ASJC) codes

  • Biophysics

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