Nagata K, Aistrup G L, Huang C S, Marszalec W, Song J H, Yeh J Z, Narahashi T
Department of Molecular Pharmacology and Biological Chemistry, Northwestern University Medical School, Chicago, IL 60611, USA.
Neurosci Lett. 1996 Oct 18;217(2-3):189-93.
Controversies remain over which ion channels are the most sensitive to ethanol. We have found that ethanol potently modulates the neuronal nicotinic acetylcholine receptor-channel at micromolar concentrations with an EC50 of 88.5 microM, which is significantly lower than most values previously reported for other ion channels. Prolonged application of ethanol accelerated the decay phase of acetylcholine-induced currents, caused single-channels to open in bursts, and shortened the mean open time, all of which reflect increased receptor desensitization. However, ethanol slowed the decay phase of the current induced by a brief application of acetylcholine, which may indicate that ethanol manifests its action by causing an increase in the affinity of the receptor for acetylcholine. These results suggest that neuronal nicotinic acetylcholine receptors may be important target sites of ethanol, particularly in the early stages of ethanol intoxication.
关于哪些离子通道对乙醇最为敏感仍存在争议。我们发现，乙醇在微摩尔浓度下就能有效调节神经元烟碱型乙酰胆碱受体通道，其半数有效浓度（EC50）为88.5微摩尔，这显著低于先前报道的其他离子通道的大多数值。长时间应用乙醇会加速乙酰胆碱诱导电流的衰减阶段，导致单通道成簇开放，并缩短平均开放时间，所有这些都反映出受体脱敏增加。然而，乙醇减缓了短暂应用乙酰胆碱所诱导电流的衰减阶段，这可能表明乙醇通过增加受体对乙酰胆碱的亲和力来发挥其作用。这些结果表明，神经元烟碱型乙酰胆碱受体可能是乙醇的重要作用靶点，尤其是在乙醇中毒的早期阶段。
