Single-channel analysis of ethanol enhancement of glycine receptor function.
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 microM glycine +/- 50 or 200 mM ethanol on outside-out patches pulled from Xenopus laevis oocytes expressing wild-type alpha1 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.
Welsh
Brian T
BT
Institute for Neuroscience, A4800, 2500 Speedway, MBB 1.148, University of Texas at Austin, Austin, TX 78712, USA. briantw@mail.utexas.edu
Goldstein
Beth E
BE
Mihic
S John
SJ
D000818:Animals; D004357:Drug Synergism; D000431:Ethanol / Q000494:pharmacology*; D005260:Female; D015640:Ion Channel Gating / Q000187:drug effects / Q000502:physiology; D009865:Oocytes / Q000378:metabolism; D018408:Patch-Clamp Techniques / Q000379:methods; D011485:Protein Binding / Q000187:drug effects / Q000502:physiology; D018009:Receptors, Glycine / Q000037:antagonists & inhibitors* / Q000378:metabolism / Q000502:physiology*; D014982:Xenopus laevis
D018009:Receptors, Glycine; D000431:Ethanol