Ethanol inhibits glutamate-induced currents in heteromeric NMDA receptor subtypes

Abstract

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.