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Acute effects of ethanol on kainate receptors in cultured hippocampal neurons
E T Costa1, E E Soto, R A Cardoso
1Department of Neurosciences, University of New Mexico Health Sciences Center, Albuquerque 87131-5223, USA.
Background:
Kainate receptors are a subclass of ionotropic glutamate receptors that regulate excitability and mediate synaptic transmission and plasticity in the hippocampus. The acute effects of ethanol on these receptors are not completely understood.
Methods:
The acute effects of ethanol on pharmacologically isolated kainate receptor-mediated currents were studied in cultured hippocampal neurons obtained from neonatal rats. Whole-cell patch-clamp electrophysiological techniques were used for these studies. LY303070 (GYKI-53784), a potent AMPA (alpha-amino-3-hydroxy-5-methylisoxazole-4-propionic acid) receptor-selective 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 reduced to 24% of control values in the presence of 15 microM lanthanum. These kainate receptor-mediated currents were significantly inhibited by ethanol concentrations of 50 mM or more. Under our recording conditions, ethanol inhibited non-NMDA receptor- and NMDA receptor-mediated currents to a similar extent as kainate receptor-mediated currents. Western blot analysis indicated 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 important targets for the actions of ethanol in the central nervous system.