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NEUROPHARMACOLOGY

Single-Channel Analysis of Ethanol Enhancement of Glycine Receptor Function

Section of Neurobiology (S.J.M.), Waggoner Center for Alcohol and Addiction Research (S.J.M.), and Institutes for Neuroscience (B.T.W., S.J.M.) and Cell and Molecular Biology (B.E.G., S.J.M.), University of Texas at Austin, Austin, Texas

The glycine receptor (GlyR) is a ligand-gated ion channel and member of the nicotinic acetylcholine receptor superfamily. Acting as allosteric modulators of receptor function, drugs such as alcohol and volatile anesthetics enhance the function of GlyRs. The actions of these drugs at inhibitory receptors in the brain and spinal cord are thought to produce many of the physiological effects associated with their use. The actions of ethanol on the GlyR have been well studied on the macroscopic, whole cell level. We examined the effects of 3 µM glycine ± 50 or 200 mM ethanol on outside-out patches pulled from Xenopus laevis oocytes expressing wild-type 1 GlyR, to determine the effects of alcohol at the single-channel level. Alcohol enhanced GlyR function in a very specific manner. It had minimal effects on open and closed dwell times and likelihood. Instead, ethanol potentiated GlyR function almost exclusively by increasing burst durations and increasing the number of channel openings per burst, without affecting the percentage of open time within bursts. Kinetic modeling suggests that ethanol increases burst durations by decreasing the rate of glycine unbinding.

Address correspondence to: Dr. Brian T. Welsh, Institute for Neuroscience, A4800, 2500 Speedway, MBB 1.148, University of Texas at Austin, Austin, TX 78712. E-mail: briantw{at}mail.utexas.edu