Click here to close
Hello! We notice that you are using Internet Explorer, which is not supported by Xenbase and may cause the site to display incorrectly.
We suggest using a current version of Chrome,
FireFox, or Safari.
Neuropharmacology
2010 Mar 01;583:676-81. doi: 10.1016/j.neuropharm.2009.11.001.
Show Gene links
Show Anatomy links
Zinc enhances ethanol modulation of the alpha1 glycine receptor.
McCracken LM
,
Trudell JR
,
Goldstein BE
,
Harris RA
,
Mihic SJ
.
???displayArticle.abstract???
Glycine receptor function mediates most inhibitory neurotransmission in the brainstem and spinal cord and is enhanced by alcohols, volatile anesthetics, inhaled drugs of abuse, and endogenous compounds including zinc. Because zinc exists ubiquitously throughout the brain, investigations of its effects on the enhancement of GlyR function by alcohols and anesthetics are important to understanding the effects of these agents in vivo. In the present study, the effects of zinc plus ethanol, pentanol, or isoflurane were tested on homomeric alpha1 glycine receptors to determine if concurrent applications of physiological concentrations of zinc with each of these modulators changed the magnitude of their effects. Homomeric alpha1 glycine receptors were expressed in Xenopus laevis oocytes, and the two-electrode voltage-clamp technique was used to measure glycine-mediated currents in the presence of combinations of zinc with ethanol, pentanol or isoflurane. The combined effects of zinc plus ethanol were greater than the sum of the effects produced by either compound alone. However, this was not seen when zinc was combined with either pentanol or isoflurane. Chelation of zinc by tricine decreased the effects of sub-maximal, but not maximal, concentrations of glycine, and diminished the magnitude of ethanol enhancement observed. These findings suggest a zinc/ethanol interaction at the alpha1 GlyR that results in the enhancement of the effects of ethanol action on GlyR function.
Beckstead,
Glycine and gamma-aminobutyric acid(A) receptor function is enhanced by inhaled drugs of abuse.
2000, Pubmed,
Xenbase
Beckstead,
Glycine and gamma-aminobutyric acid(A) receptor function is enhanced by inhaled drugs of abuse.
2000,
Pubmed
,
Xenbase
Choi,
Zinc and brain injury.
1998,
Pubmed
Crawford,
Evidence that ethanol acts on a target in Loop 2 of the extracellular domain of alpha1 glycine receptors.
2007,
Pubmed
,
Xenbase
Davies,
Multiple sites of ethanol action in alpha1 and alpha2 glycine receptors suggested by sensitivity to pressure antagonism.
2004,
Pubmed
,
Xenbase
Doraiswamy,
Metals in our minds: therapeutic implications for neurodegenerative disorders.
2004,
Pubmed
Fatima-Shad,
Anion permeation in GABA- and glycine-gated channels of mammalian cultured hippocampal neurons.
1993,
Pubmed
Frederickson,
Concentrations of extracellular free zinc (pZn)e in the central nervous system during simple anesthetization, ischemia and reperfusion.
2006,
Pubmed
Frederickson,
Synaptically released zinc: physiological functions and pathological effects.
2001,
Pubmed
Harvey,
Identification of an inhibitory Zn2+ binding site on the human glycine receptor alpha1 subunit.
1999,
Pubmed
Hirzel,
Hyperekplexia phenotype of glycine receptor alpha1 subunit mutant mice identifies Zn(2+) as an essential endogenous modulator of glycinergic neurotransmission.
2006,
Pubmed
Jenkins,
General anesthetics have additive actions on three ligand gated ion channels.
2008,
Pubmed
,
Xenbase
Jones,
Genetic analysis reveals polygenic influences on iron, copper, and zinc in mouse hippocampus with neurobiological implications.
2008,
Pubmed
Kay,
Detecting and minimizing zinc contamination in physiological solutions.
2004,
Pubmed
Laube,
Modulation by zinc ions of native rat and recombinant human inhibitory glycine receptors.
1995,
Pubmed
,
Xenbase
Laube,
Kinetic and mutational analysis of Zn2+ modulation of recombinant human inhibitory glycine receptors.
2000,
Pubmed
,
Xenbase
Legendre,
The glycinergic inhibitory synapse.
2001,
Pubmed
Lobo,
Accessibility to residues in transmembrane segment four of the glycine receptor.
2006,
Pubmed
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,
Channel gating of the glycine receptor changes accessibility to residues implicated in receptor potentiation by alcohols and anesthetics.
2004,
Pubmed
,
Xenbase
Lynch,
Molecular structure and function of the glycine receptor chloride channel.
2004,
Pubmed
Mascia,
Specific binding sites for alcohols and anesthetics on ligand-gated ion channels.
2000,
Pubmed
,
Xenbase
Mathie,
Zinc and copper: pharmacological probes and endogenous modulators of neuronal excitability.
2006,
Pubmed
Mihic,
Sites of alcohol and volatile anaesthetic action on GABA(A) and glycine receptors.
1997,
Pubmed
,
Xenbase
Miller,
Molecular determinants of glycine receptor alphabeta subunit sensitivities to Zn2+-mediated inhibition.
2005,
Pubmed
Miller,
Molecular basis for zinc potentiation at strychnine-sensitive glycine receptors.
2005,
Pubmed
Molander,
Involvement of accumbal glycine receptors in the regulation of voluntary ethanol intake in the rat.
2005,
Pubmed
Molander,
Accumbal strychnine-sensitive glycine receptors: an access point for ethanol to the brain reward system.
2005,
Pubmed
Molander,
The glycine reuptake inhibitor Org 25935 decreases ethanol intake and preference in male wistar rats.
2007,
Pubmed
Paoletti,
Zinc at glutamatergic synapses.
2009,
Pubmed
Suwa,
High-affinity zinc potentiation of inhibitory postsynaptic glycinergic currents in the zebrafish hindbrain.
2001,
Pubmed
Takahashi,
Functional correlation of fetal and adult forms of glycine receptors with developmental changes in inhibitory synaptic receptor channels.
1992,
Pubmed
,
Xenbase
Wang,
Inhibitory zinc-enriched terminals in the mouse cerebellum: double-immunohistochemistry for zinc transporter 3 and glutamate decarboxylase.
2002,
Pubmed
Welsh,
Single-channel analysis of ethanol enhancement of glycine receptor function.
2009,
Pubmed
,
Xenbase
Yevenes,
A selective G betagamma-linked intracellular mechanism for modulation of a ligand-gated ion channel by ethanol.
2008,
Pubmed
Yevenes,
Modulation of glycine-activated ion channel function by G-protein betagamma subunits.
2003,
Pubmed
van den Pol,
Glycine and glycine receptor immunoreactivity in brain and spinal cord.
1988,
Pubmed
