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Multiple sites of ethanol action in α1 and α2 glycine receptors suggested by sensitivity to pressure antagonism
Author(s) -
Davies Daryl L.,
Crawford Daniel K.,
Trudell James R.,
Mihic S. John,
Alkana Ronald L.
Publication year - 2004
Publication title -
journal of neurochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.75
H-Index - 229
eISSN - 1471-4159
pISSN - 0022-3042
DOI - 10.1111/j.1471-4159.2004.02390.x
Subject(s) - glycine receptor , ethanol , chemistry , glycine , antagonism , long term potentiation , biophysics , receptor , biochemistry , pharmacology , biology , amino acid
The current study used an ethanol antagonist, increased atmospheric pressure, to test the hypothesis that ethanol acts on multiple sites in glycine receptors (GlyRs). The effects of 12 times normal atmospheric pressure of helium‐oxygen gas (pressure) on ethanol‐induced potentiation of GlyR function in Xenopus oocytes expressing human α1, α2 or the mutant α1(A52S) GlyRs were measured using two‐electrode voltage clamp. Pressure reversibly antagonized potentiation of glycine in α1 GlyR by 40–200 m m ethanol, but did not antagonize 10 and 25 m m ethanol in the same oocytes. In contrast, pressure did not significantly affect potentiation of glycine by 25–100 m m ethanol in α2 GlyRs, nor did pressure alter ethanol response in the A52S mutant. Pressure did not affect baseline receptor function or response to glycine in the absence of ethanol. These findings provide the first direct evidence for multiple sites of ethanol action in GlyRs. The sites can be differentiated on the basis of ethanol concentration, subunit and structural composition and sensitivities to pressure antagonism of ethanol. Parallel studies with butanol support this conclusion. The mutant α1(A52S) GlyR findings suggest that increased attention should be focused on the amino terminus as a potential target for ethanol action.