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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 50 mM both in Ca2 -containing and Ca2 -deficient, Ba2 -containing Mg2 -free media. The NR1-NR2C channels were slightly less sensitive to ethanol inhibition than the other heteromeric channels in Ca2 -deficient, Ba2 -containing medium. The inhibition was unaffected by the clamping-voltage and by a mutaion [NR1-NR2A(N595Q)] that prevents the Mg2 -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.

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