ACUTE EFFECTS OF ETHANOL ON PHARMACOLOGICALLY ISOLATED KAINATE RECEPTORS IN CEREBELLAR GRANULE NEURONS - COMPARISON WITH NMDA AND AMPA RECEPTORS

Comparisons of acute ethanol's effects on individual members of the th ree major families of ionotropic glutamate receptors (kainate, AMPA, a nd NMDA) have been performed only with recombinant receptors. However, no study has compared the acute effects of ethanol on individual memb ers of each one of these receptor families in the same neuron. We acco mplished this task by using cultured cerebellar granule neurons and LY 303070 (GYKI-53784), a noncompetitive and selective AMPA receptor anta gonist. Ethanol concentrations of 25, 50, 75, and 100 mM decreased the amplitude of pharmacologically isolated kainate-activated currents by 3 +/- 1, 9 +/- 2, 14 +/- 2, and 22 +/- 3% (n = 8), respectively. The magnitude of the ethanol-induced inhibition of nonselective kainate-ac tivated currents, i.e., in the absence of LY303070, and currents activ ated by submaximal AMPA concentrations was not significantly different from that obtained with isolated kainate currents. However, tie magni tude of the ethanol-induced inhibition of NMDA receptor-activated curr ents was about twofold greater than that of kainate and/or AMPA recept ors.