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Protons Activate Brain Na+Channel 1 by Inducing a Conformational Change That Exposes a Residue Associated with Neurodegeneration
Journal article   Open access   Peer reviewed

Protons Activate Brain Na+Channel 1 by Inducing a Conformational Change That Exposes a Residue Associated with Neurodegeneration

Christopher M Adams, Peter M Snyder, Margaret P Price and Michael J Welsh
The Journal of biological chemistry, Vol.273(46), pp.30204-30207
11/13/1998
DOI: 10.1074/jbc.273.46.30204
PMID: 9804777
url
https://doi.org/10.1074/jbc.273.46.30204View
Published (Version of record) Open Access

Abstract

BNC1 is a mammalian neuronal cation channel in the novel DEG/ENaC ion channel family. BNC1 channels are transiently activated by extracellular protons and are constitutively activated by insertion of large residues, such as valine, in place of Gly-430; residue 430 is a site where analogous mutations in some Caenorhabditis elegans family members cause a swelling neurodegeneration. Mutation of Gly-430 to a small amino acid, cysteine, neither generated constitutive currents nor allowed modification of this residue by sulfhydryl-reactive methanethiosulfonate (MTS) compounds. However, when protons activated the channel, Cys-430 became accessible to extracellular MTS reagents, which modified Cys-430 to generate constitutive currents. Fluorescent MTS reagents also labeled Cys-430 in activated channels. These data indicate that protons induce a reversible conformational change that activates BNC1 thereby exposing residue 430 to the extracellular solution. Once Cys-430 is modified with a large chemical group, the channel is prevented from relaxing back to the inactive state. These results link ligand-dependent activation and activation by mutations that cause neurodegeneration.

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