Ethanol inhibits NMDA-activated ion current in hippocampal neurons.
The ion current induced by the glutamate receptor agonist N-methyl-D-aspartate (NMDA) in voltage-clamped hippocampal neurons was inhibited by ethanol (EtOH). Inhibition increased in a concentration-dependent manner over the range 5 to 50 mM, a range that also produces intoxication. The amplitude of the NMDA-activated current was reduced 61 percent by 50 mM EtOH; in contrast, this concentration of EtOH reduced the amplitude of current activated by the glutamate receptor agonists kainate and quisqualate by only 18 and 15 percent, respectively. The potency for inhibition of the NMDA-activated current by several alcohols is linearly related to their intoxicating potency, suggesting that alcohol-induced inhibition of responses to NMDA receptor activation may contribute to the neural and cognitive impairments associated with intoxication.
Lovinger
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DM
Section of Electrophysiology, National Institute on Alcohol Abuse and Alcoholism, Rockville, MD 20852.
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D020001:1-Butanol; D001224:Aspartic Acid / Q000031:analogs & derivatives* / Q000494:pharmacology; D000440:Butanols / Q000494:pharmacology; D015220:Calcium Channels / Q000187:drug effects / Q000502:physiology; D018118:Chloride Channels; D002712:Chlorides / Q000502:physiology; D004553:Electric Conductivity; D000431:Ethanol / Q000009:adverse effects / Q000494:pharmacology*; D006624:Hippocampus / Q000166:cytology / Q000502:physiology*; D006801:Humans; D007473:Ion Channels / Q000187:drug effects / Q000502:physiology*; D007608:Kainic Acid / Q000494:pharmacology; D008565:Membrane Proteins / Q000502:physiology; D000432:Methanol / Q000494:pharmacology; D016202:N-Methylaspartate; D009474:Neurons / Q000502:physiology*; D010069:Oxadiazoles / Q000494:pharmacology; D000439:Pentanols / Q000494:pharmacology; D016318:Quisqualic Acid; D017470:Receptors, Glutamate; D016194:Receptors, N-Methyl-D-Aspartate; D017981:Receptors, Neurotransmitter / Q000187:drug effects / Q000502:physiology; D015222:Sodium Channels / Q000187:drug effects / Q000502:physiology; D005680:gamma-Aminobutyric Acid / Q000494:pharmacology
D000440:Butanols; D015220:Calcium Channels; D018118:Chloride Channels; D002712:Chlorides; D007473:Ion Channels; D008565:Membrane Proteins; D010069:Oxadiazoles; D000439:Pentanols; D017470:Receptors, Glutamate; D016194:Receptors, N-Methyl-D-Aspartate; D017981:Receptors, Neurotransmitter; D015222:Sodium Channels; D001224:Aspartic Acid; D000431:Ethanol; D005680:gamma-Aminobutyric Acid; D016202:N-Methylaspartate; D016318:Quisqualic Acid; D020001:1-Butanol; C029683:isopentyl alcohol; D007608:Kainic Acid; D000432:Methanol