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Mutations of the α1 Glycine Receptor Subunit Regulate Sensitivity to Alcohols

Journal of Pharmacology and Experimental Therapeutics February 2012, 340 (2) 227;
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Glycine receptors (GlyRs) are inhibitory ligand-gated ion channels, and ethanol has the ability to potentiate glycine activation of the GlyR. Borghese et al. investigated the putative binding sites for alcohol (alteration of ethanol sensitivity) by introducing two mutations in the GlyR α1 subunit, M287L [transmembrane domain (TM) 3] and Q266I (TM2). Both mutants showed a reduction in glycine sensitivity and glycine-induced maximal currents. Activation by taurine, another endogenous agonist, was almost abolished in the M287L GlyR. Zinc enhancement of ethanol potentiation of glycine responses was absent in M287L GlyRs. Survival of homozygous knockin mice was impaired, and electrophysiological features of isolated neurons in the brain stem showed decreased glycine-mediated currents and decreased ethanol potentiation. This study suggests that many of the basic characteristics, such as channel properties, present in mutated GlyRs expressed in Xenopus laevis oocytes and human embryonic kidney 293 cells were similar to those observed in isolated neurons and membrane preparations from the corresponding knockin mice: 1) a small but general impairment of glycine action, most evident in the glycine-induced maximal currents, and 2) lack of sensitivity to ethanol.

See article at J Pharmacol Exp Ther 2012, 340:304–316.

  • Copyright © 2012 by The American Society for Pharmacology and Experimental Therapeutics
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Journal of Pharmacology and Experimental Therapeutics: 340 (2)
Journal of Pharmacology and Experimental Therapeutics
Vol. 340, Issue 2
1 Feb 2012
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Mutations of the α1 Glycine Receptor Subunit Regulate Sensitivity to Alcohols

Journal of Pharmacology and Experimental Therapeutics February 1, 2012, 340 (2) 227;

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Mutations of the α1 Glycine Receptor Subunit Regulate Sensitivity to Alcohols

Journal of Pharmacology and Experimental Therapeutics February 1, 2012, 340 (2) 227;
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