Abstract
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 α1 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.
Footnotes
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This work was supported by the National Institutes of Health National Institute on Alcohol Abuse and Alcoholism [Grants R01-AA11525, T32-AA007471]; and by a Bruce/Jones Predoctoral Fellowship.
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Article, publication date, and citation information can be found at http://jpet.aspetjournals.org.
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doi:10.1124/jpet.109.154344.
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ABBREVIATIONS: GlyR, glycine receptor; TM, transmembrane; EtOH, ethanol; MBS, modified Barth's saline; MIL, maximal interval likelihood; ANOVA, analysis of variance; Popen, probability of channel being open; AR, GlyR with a single glycine molecule bound; BEC, blood ethanol concentration; Org 25935, cis-N-methyl-N-(6-methoxy-1-phenyl-1,2,3,4-tetrahydronaphthalen-2-yl methyl)amino methylcarboxylic acid.
- Received March 29, 2009.
- Accepted April 17, 2009.
- The American Society for Pharmacology and Experimental Therapeutics
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