Studies have shown that the effect of ethanol on glycine receptors (GlyRs) containing the α1 subunit is affected by interaction with heterotrimeric G proteins (Gβγ). It is unknown, however, whether ethanol affects the function of GlyRs containing the α3 subunit. Electrophysiological experiments showed that GlyR α3 subunits were not potentiated by pharmacological concentrations of ethanol or by Gβγ. Mutation of corresponding glycine 254 in transmembrane domain 2 (TM2) found in α1 in the α3A254G–α1 chimera induced a glycine-evoked current that displayed potentiation during application of ethanol and Gβγ activation. Interestingly, insertion of the intracellular α3L splice cassette into GlyR α1 abolished the enhancement of the glycine-activated current by ethanol and activation by Gβγ. These data demonstrate that GlyR α3 subunits are not modulated by ethanol. Residue A254 in TM2, the α3L splice cassette, and the C terminus domain of α3 GlyRs are determinants for low ethanol sensitivity and form the molecular basis of subtype-selective modulation of GlyRs by alcohol.
See article at J Pharmacol Exp Ther 2015, 353:80–90.
- Copyright © 2015 by The American Society for Pharmacology and Experimental Therapeutics