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.