Ethanol modulation of nicotinic acetylcholine receptor currents in cultured cortical neurons
Ethanol modulation of nicotinic acetylcholine receptor currents in cultured cortical neurons
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DOI：
10.1124/mol.55.1.39
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发表时间：
1999-01-01
影响因子：
3.6
通讯作者：
Narahashi, T
中科院分区：
文献类型：
--
作者：
Aistrup, GL;Marszalec, W;Narahashi, T
乙醇，在生理相关的浓度，显着增强高亲和力神经元烟碱乙酰胆碱受体（NnAChR）电流不敏感的ol-银环蛇毒素（（α-BuTX-IC）在培养的大鼠皮层神经元在一个快速和可逆的方式，通过标准的全细胞膜片钳记录技术。增强为（平均值+/- S.D.）7.7+/- 5%至192 +/- 52%，共施用3至300 mM乙醇和1至3 μ M ACh。达到该乙醇诱导的α-BuTX-IC增强的NO平台。最大的α-BuTX-IC诱发非常高浓度的乙酰胆碱也增加后，乙醇的共同应用。相比之下，乙醇弱抑制对α-BuTX敏感的低亲和力NnAChR电流（α-BuTX-SC）（在300至1000 μ M ACh下，IO至300 mM乙醇的抑制率为5 +/- 4%至29 +/- 6%）。这种神经元制备也使得乙醇对NnAChRs的作用与其对相同神经元内的N-甲基-D-天冬氨酸受体电流和γ-氨基丁酸受体电流的作用能够进行比较。乙醇（100 mM）在增强NnAChR α-BuTX-IC（61 +/- 9%增强）方面比增强γ-氨基丁酸受体电流（3 +/- 3%增强-无统计学显著性）或抑制N-甲基-D-天冬氨酸受体电流（类似于35 +/- 7%抑制）更有效。因此，NnAChRs，特别是那些对α-BuTX不敏感的，可能是敏感的管道，通过它乙醇可以介导它在大脑中的一些作用。
Ethanol, at physiologically relevant concentrations, significantly enhanced high-affinity neuronal nicotinic acetylcholine receptor (NnAChR) currents insensitive to ol-bungarotoxin ((alpha-BuTX-ICs) in cultured rat cortical neurons in a fast and reversible manner, as determined by standard whole-cell patch-clamp recording techniques. The enhancement was (mean +/- S.D.) 7.7 +/- 5% to 192 +/- 52% upon coapplication of 3 to 300 mM ethanol with 1 to 3 mu M ACh. NO plateau for this ethanol-induced enhancement of alpha-BuTX-ICs was reached. The maximal alpha-BuTX-IC evoked by very high concentrations of ACh also was increased upon coapplication of ethanol. In contrast, ethanol weakly inhibited low-affinity NnAChR currents sensitive to alpha-BuTX (alpha-BuTX-SCs) (5 +/- 4% to 29 +/- 6% inhibition by IO to 300 mM ethanol at 300 to 1000 mu M ACh). This neuronal preparation also enabled comparison of ethanol action on NnAChRs with its action on N-methyl-D-aspartate receptor currents and gamma-aminobutyric acid receptor currents within the same neurons. Ethanol (100 mM) was more potent at enhancing NnAChR alpha-BuTX-ICs(61 +/- 9% enhancement) than it was at enhancing gamma-aminobutyric acid receptor current (3 +/- 3% enhancement-not statistically significant) or at inhibiting N-methyl-D-aspartate receptor currents (similar to 35 +/- 7% inhibition). Thus, NnAChRs, particularly those insensitive to alpha-BuTX, may be sensitive conduits through which ethanol can mediate some of its actions in the brain.