Costa E T, Soto E E, Cardoso R A, Olivera D S, Valenzuela C F
Department of Neurosciences, University of New Mexico Health Sciences Center, Albuquerque 87131-5223, USA.
Alcohol Clin Exp Res. 2000 Feb;24(2):220-5.
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.
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.
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.
The present results suggest that kainate receptors are important targets for the actions of ethanol in the central nervous system.
海人酸受体是离子型谷氨酸受体的一个亚类，可调节兴奋性并介导海马体中的突触传递和可塑性。乙醇对这些受体的急性作用尚未完全明确。
在从新生大鼠获取的培养海马神经元中，研究乙醇对药理学分离的海人酸受体介导电流的急性作用。这些研究采用全细胞膜片钳电生理技术。使用强效AMPA（α-氨基-3-羟基-5-甲基异恶唑-4-丙酸）受体选择性非竞争性拮抗剂LY303070（GYKI-53784）来分离海人酸电流。
在这些神经元中，海人酸受体介导的电流占总非N-甲基-D-天冬氨酸（非NMDA）电流的7%，在存在15微摩尔镧的情况下降至对照值的24%。这些海人酸受体介导的电流在乙醇浓度达到50毫摩尔或更高时受到显著抑制。在我们的记录条件下，乙醇对非NMDA受体和NMDA受体介导电流的抑制程度与海人酸受体介导电流相似。蛋白质印迹分析表明，谷氨酸受体5和-6/7亚基以及海人酸-2亚基在这些培养的海马神经元中表达。
目前的结果表明，海人酸受体是乙醇在中枢神经系统中作用的重要靶点。
