期刊
ALCOHOLISM-CLINICAL AND EXPERIMENTAL RESEARCH
卷 24, 期 2, 页码 220-225出版社
LIPPINCOTT WILLIAMS & WILKINS
DOI: 10.1097/00000374-200002000-00013
关键词
glutamate; alcohol; ionotropic; channel; neurotransmitter
资金
- NIAAA NIH HHS [AA00227] Funding Source: Medline
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 fr om 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 mu M 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.
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