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Acetylcholine receptor gating is influenced by the polarity of amino acids at position 9' in the M2 domain
Journal article   Peer reviewed

Acetylcholine receptor gating is influenced by the polarity of amino acids at position 9' in the M2 domain

A V Kosolapov, G N Filatov and M M White
The Journal of membrane biology, v 174(3), pp 191-197
01 Apr 2000
PMID: 10758172

Abstract

Xenopus Cell Line Animals Receptors, Cholinergic - metabolism Humans Mice Binding Sites Ion Channel Gating Amino Acid Substitution Receptors, Cholinergic - genetics
Ligand-gated ion channels contain a conserved leucine at position 9' (L9') in the M2 transmembrane domain. We used multiple substitutions at this position in the gamma subunit of the mouse acetylcholine receptor (AChR) (gammaL9') to examine the role of residue polarity at this position in the gating process at both the macroscopic and single-channel levels. The midpoint of the macroscopic dose-response relationship (EC(50)) and the channel closing rate constant, alpha, decreased as the polarity of the residue at that position increased, suggesting a stabilization of the open state of the channel. Both parameters showed similar dependencies on the polarity of the substituted residue. These data support the notion that during AChR gating, the amino acid at the 9' position moves into a polar environment, and that interactions between this residue and the polar environment determine the stability of the open state. Since this residue is conserved in all other members of the ligand-gated ion channel family, we suggest that a similar mechanism applies to the other members of the family.

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Web of Science research areas
Biochemistry & Molecular Biology
Cell Biology
Physiology
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