Acute effects of ethanol on kainate receptors in cultured hippocampal neurons

Background: Kainate receptors are a subclass of ionotropic glutamate recept ors that regulate excitability and mediate synaptic transmission and plasti city in the hippocampus. The acute effects of ethanol on these receptors ar e not completely understood. Methods: The acute effects of ethanol on pharmacologically isolated kainate receptor-mediated currents were studied in cultured hippocampal neurons ob tained fr om neonatal rats. Whole-cell patch-clamp electrophysiological tec hniques were used for these studies. LY303070 (GYKI-53784), a potent AMPA ( alpha-amino-3-hydroxy-5-methylisoxazole-4-propionic acid) receptor-selectiv e noncompetitive antagonist, was used to isolate kainate currents. Results: Kainate receptor-mediated currents corresponded to 7% of the total non-N-methyl-D-aspartate (non-NMDA) currents in these neurons and were red uced to 24% of control values in the presence of 15 mu M lanthanum. These k ainate receptor-mediated currents were significantly inhibited by ethanol c oncentrations of 50 mM or more. Under our recording conditions, ethanol inh ibited non-NMDA receptor- and NMDA receptor-mediated currents to a similar extent as kainate receptor-mediated currents. Western blot analysis indicat ed that glutamate receptor-5 and -6/7 subunits, and kainic acid-2 subunits are expressed in these cultured hippocampal neurons. Conclusions: The present results suggest that kainate receptors are importa nt targets for the actions of ethanol in the central nervous system.