Anesthetic and ethanol effects on spontaneously opening glycine receptor channels

Strychnine‐sensitive glycine receptors mediate inhibitory neurotransmission occurring in the brain stem and spinal cord. Alcohols, volatile anesthetics and inhaled drugs of abuse are positive allosteric modulators of glycine receptor function, normally enhancing function only in the presence of glyc...

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Bibliographic Details
Published inJournal of neurochemistry Vol. 82; no. 6; pp. 1343 - 1351
Main Authors Beckstead, Michael J., Phelan, Rachel, Trudell, James R., Bianchini, Michael J., Mihic, S. John
Format Journal Article
LanguageEnglish
Published Oxford, UK Blackwell Science Ltd 01.09.2002
Blackwell
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Summary:Strychnine‐sensitive glycine receptors mediate inhibitory neurotransmission occurring in the brain stem and spinal cord. Alcohols, volatile anesthetics and inhaled drugs of abuse are positive allosteric modulators of glycine receptor function, normally enhancing function only in the presence of glycine. A complication in studying allosteric actions on ligand‐gated ion channels is in the dissection of their effects on neurotransmitter binding from their effects on channel opening. Mutation of an aspartate residue at position 97 to arginine in the glycine receptor α1 subunit simulated the effects of glycine binding, producing receptors that exhibited tonic channel opening in the absence of neurotransmitter; i.e. these receptors demonstrated a dissociation of channel opening from neurotransmitter binding. In these receptors, ethanol, enflurane, chloroform, halothane, 1,1,1‐trichloroethane and toluene elicited inward currents in the absence of glycine. We previously identified mutations on ligand‐gated ion channels that eliminate ethanol, anesthetic and inhalant actions (such as S267I on α1 glycine receptors). The double mutant (D97R and S267I) receptors were both constitutively active and resistant to the enhancing effects of ethanol and enflurane. These data demonstrate that ethanol and volatile anesthetics can affect glycine receptor channel opening independently of their effects on enhancing neurotransmitter binding.
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ISSN:0022-3042
1471-4159
DOI:10.1046/j.1471-4159.2002.01086.x