Ethanol inhibits glutamate-induced currents in heteromeric NMDA receptor subtypes.
Maximal L-glutamate/glycine-evoked currents were inhibited by ethanol in Xenopus laevis oocytes expressing recombinant heteromeric NMDA receptors consisting of NR1-NR2A, NR1-NR2B, and NR1-NR2C subunit combinations. Concentration-dependent inhibition was observed at ethanol concentrations of > or = 50 mM both in Ca(2+)-containing and Ca(2+)-deficient, Ba(2+)-containing Mg(2+)-free media. The NR1-NR2C channels were slightly less sensitive to ethanol inhibition than the other heteromeric channels in Ca(2+)-deficient, Ba(2+)-containing medium. The inhibition was unaffected by the clamping-voltage and by a mutation [NR1-NR2A(N595Q)] that prevents the Mg(2+)-blockade of the channels, indicating that the mechanism of action of ethanol differs from that of Mg2+. The results are consistent with the hypothesis that the NMDA receptor subtypes can mediate many behavioural actions of ethanol.
Kuner
T
T
Laboratory of Molecular Neuroendocrinology, University of Heidelberg, Germany.
Schoepfer
R
R
Korpi
E R
ER
D000818:Animals; D003001:Cloning, Molecular; D000431:Ethanol / Q000494:pharmacology*; D018691:Excitatory Amino Acid Antagonists; D005971:Glutamates / Q000494:pharmacology; D018698:Glutamic Acid; D005998:Glycine / Q000494:pharmacology; D009865:Oocytes / Q000187:drug effects / Q000378:metabolism; D016194:Receptors, N-Methyl-D-Aspartate / Q000037:antagonists & inhibitors*; D014981:Xenopus
D018691:Excitatory Amino Acid Antagonists; D005971:Glutamates; D016194:Receptors, N-Methyl-D-Aspartate; D000431:Ethanol; D018698:Glutamic Acid; D005998:Glycine