The basic property of Lys385 is important for potentiation of the human α1 glycine receptor by ethanol.

ABSTRACT: Ethanol alters the function of several members of the Cys-loop ligand-gated ion channel superfamily. Recent studies have shown that the sensitivity of the α1 glycine receptor (GlyR) to ethanol can be affected by the state of G protein activation mediated by the interaction of Gβγ with intracellular amino acids in the GlyR. Here, we evaluated the physicochemical property of Lys385 that contributes to ethanol modulation by using mutagenesis, patch-clamp, and biochemical techniques. A conserved substitution (K385R) did not affect either the apparent glycine EC₅₀ (40 ± 1 versus 41 ± 0.5 μM) or the ethanol-induced potentiation (53 ± 5 versus 46 ± 5%) of the human α1 GlyR. On the other hand, replacement of this residue with glutamic acid (K385E), an acidic amino acid, reduced the potentiation of

SUBMITTER: Castro PA 

PROVIDER: S-EPMC3263957 | biostudies-literature | 2012 Feb

REPOSITORIES: biostudies-literature