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Single-channel analysis of ethanol enhancement of glycine receptor function.
Welsh BT
,
Goldstein BE
,
Mihic SJ
.
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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.
Aguayo,
Potentiation of the glycine-activated Cl- current by ethanol in cultured mouse spinal neurons.
1996, Pubmed
Aguayo,
Potentiation of the glycine-activated Cl- current by ethanol in cultured mouse spinal neurons.
1996,
Pubmed
Aguayo,
Ethanol modulation of the gamma-aminobutyric acidA- and glycine-activated Cl- current in cultured mouse neurons.
1994,
Pubmed
Akk,
Mutations of the GABA-A receptor alpha1 subunit M1 domain reveal unexpected complexity for modulation by neuroactive steroids.
2008,
Pubmed
Beato,
Openings of the rat recombinant alpha 1 homomeric glycine receptor as a function of the number of agonist molecules bound.
2002,
Pubmed
Beato,
The activation mechanism of alpha1 homomeric glycine receptors.
2004,
Pubmed
Betz,
Glycine receptors: heterogeneous and widespread in the mammalian brain.
1991,
Pubmed
Celentano,
Ethanol potentiates GABA- and glycine-induced chloride currents in chick spinal cord neurons.
1988,
Pubmed
Cheng,
Molecular dynamics simulations of ethanol binding to the transmembrane domain of the glycine receptor: implications for the channel potentiation mechanism.
2008,
Pubmed
Crawford,
Evidence that ethanol acts on a target in Loop 2 of the extracellular domain of alpha1 glycine receptors.
2007,
Pubmed
,
Xenbase
Deitrich,
Phenotypic and genotypic relationships between ethanol tolerance and sensitivity in mice selectively bred for initial sensitivity to ethanol (SS and LS) or development of acute tolerance (HAFT and LAFT).
2000,
Pubmed
Eggers,
Mechanisms for the modulation of native glycine receptor channels by ethanol.
2004,
Pubmed
Engblom,
Effect of ethanol on gamma-aminobutyric acid and glycine receptor-coupled Cl- fluxes in rat brain synaptoneurosomes.
1991,
Pubmed
Fang,
Maturation decreases ethanol minimum alveolar anesthetic concentration (MAC) more than desflurane MAC in rats.
1997,
Pubmed
Findlay,
Transgenic expression of a mutant glycine receptor decreases alcohol sensitivity of mice.
2002,
Pubmed
,
Xenbase
Hamill,
Improved patch-clamp techniques for high-resolution current recording from cells and cell-free membrane patches.
1981,
Pubmed
Laube,
Kinetic and mutational analysis of Zn2+ modulation of recombinant human inhibitory glycine receptors.
2000,
Pubmed
,
Xenbase
Lobo,
Channel gating of the glycine receptor changes accessibility to residues implicated in receptor potentiation by alcohols and anesthetics.
2004,
Pubmed
,
Xenbase
Lobo,
Cross-linking of sites involved with alcohol action between transmembrane segments 1 and 3 of the glycine receptor following activation.
2008,
Pubmed
,
Xenbase
Lobo,
Accessibility to residues in transmembrane segment four of the glycine receptor.
2006,
Pubmed
Lynch,
Molecular structure and function of the glycine receptor chloride channel.
2004,
Pubmed
Magleby,
Burst kinetics of single calcium-activated potassium channels in cultured rat muscle.
1983,
Pubmed
Mascia,
Specific binding sites for alcohols and anesthetics on ligand-gated ion channels.
2000,
Pubmed
,
Xenbase
Mascia,
Enhancement of homomeric glycine receptor function by long-chain alcohols and anaesthetics.
1996,
Pubmed
,
Xenbase
Mascia,
A single amino acid determines differences in ethanol actions on strychnine-sensitive glycine receptors.
1996,
Pubmed
,
Xenbase
Mihic,
Sites of alcohol and volatile anaesthetic action on GABA(A) and glycine receptors.
1997,
Pubmed
,
Xenbase
Molander,
The glycine reuptake inhibitor Org 25935 decreases ethanol intake and preference in male wistar rats.
2007,
Pubmed
Molander,
Accumbal strychnine-sensitive glycine receptors: an access point for ethanol to the brain reward system.
2005,
Pubmed
Molander,
Involvement of accumbal glycine receptors in the regulation of voluntary ethanol intake in the rat.
2005,
Pubmed
Qin,
A direct optimization approach to hidden Markov modeling for single channel kinetics.
2000,
Pubmed
Qin,
Hidden Markov modeling for single channel kinetics with filtering and correlated noise.
2000,
Pubmed
Quinlan,
Mice with glycine receptor subunit mutations are both sensitive and resistant to volatile anesthetics.
2002,
Pubmed
Rajendra,
Molecular mechanisms of inherited startle syndromes.
1995,
Pubmed
Sharko,
Differential modulation of ethanol-induced sedation and hypnosis by metabotropic glutamate receptor antagonists in C57BL/6J mice.
2008,
Pubmed
Steinbach,
Modulation of GABA(A) receptor channel gating by pentobarbital.
2001,
Pubmed
Tapia,
Ethanol affects the function of a neurotransmitter receptor protein without altering the membrane lipid phase.
1998,
Pubmed
Wick,
Mutations of gamma-aminobutyric acid and glycine receptors change alcohol cutoff: evidence for an alcohol receptor?
1998,
Pubmed
,
Xenbase
Williams,
Glycine enhances the central depressant properties of ethanol in mice.
1995,
Pubmed
Ye,
Ethanol potentiation of glycine-induced responses in dissociated neurons of rat ventral tegmental area.
2001,
Pubmed
