Post-junctional interactions between neuromuscular blocking agents and ethanol at the mouse neuromuscular junction.
Post-junctional interactions between neuromuscular blocking agents and ethanol at the mouse neuromuscular junction.
复制标题
神经肌肉阻断剂和乙醇在小鼠神经肌肉接头处的连接后相互作用。
DOI：
10.1111/j.1476-5381.2010.00904.x
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发表时间：
2010
影响因子：
7.3
通讯作者：
Silinsky,EM
中科院分区：
文献类型：
--
作者：
Searl,TJ;Silinsky,EM
背景和目的已知乙醇在哺乳动物神经系统的一系列位点（包括神经肌肉连接处）具有突触前和突触后作用。然而，乙醇对诱发突触传递的影响尚未在小鼠神经肌肉连接处进行研究。在这里，我们报道了乙醇对诱发神经肌肉传递的影响以及乙醇与非去极化阻断药物的相互作用。实验方法本研究采用电生理技术测量突触电位和突触电流。关键结果乙醇（≥100 mM）使自发突触事件和诱发突触事件的振幅都增加。在神经肌肉传递被（+）‐管curarine阻断的条件下，乙醇（12-100 mM）产生的诱发反应幅度比没有（+）‐管curarine时记录的自发反应幅度更大。在低钙/高镁溶液中，乙醇（100 mM）不影响诱发的神经递质释放。在临床使用的神经肌肉阻断药物中，乙醇（100 mM）对维库溴铵的阻断作用有干扰，对顺阿曲库铵无干扰。结论和意义在这些条件下，乙醇对神经肌肉传递的刺激作用仅作用于连接后元件，既可以通过尼古丁受体增强传递，也可以通过与神经肌肉阻断剂的相互作用增强传递。乙醇对神经肌肉传导的这些作用可能会影响大量饮酒患者所需的神经肌肉阻滞剂的剂量。
BACKGROUND AND PURPOSEEthanol is known to have both pre‐synaptic and post‐synaptic effects at a range of loci in the mammalian nervous system, including the neuromuscular junction. However, the effects of ethanol on evoked synaptic transmission have not been previously studied at the mouse neuromuscular junction. Here, we report on the effects of ethanol on evoked neuromuscular transmission and the interaction of ethanol with non‐depolarizing blocking drugs.EXPERIMENTAL APPROACHElectrophysiological techniques to measure synaptic potentials and synaptic currents were employed in this study.KEY RESULTSEthanol (≥100 mM) produced increases in the amplitudes of both spontaneous and evoked synaptic events. Under conditions in which neuromuscular transmission was blocked by (+)‐tubocurarine, ethanol (12–100 mM) produced greater increases in evoked response amplitude than in spontaneous response amplitude recorded in the absence of (+)‐tubocurarine. Ethanol (100 mM) did not affect evoked neurotransmitter release in low‐calcium/high‐magnesium solutions. With respect to the clinically used neuromuscular blocking drugs, ethanol (100 mM) interfered with the blocking action of vecuronium, but not cisatracurium.CONCLUSIONS AND IMPLICATIONSUnder these conditions, the stimulant effect of ethanol on neuromuscular transmission is exclusively on the post‐junctional elements, both to enhance transmission through nicotinic receptors and also via interactions with neuromuscular blocking agents. These actions of ethanol on neuromuscular transmission may affect the dosage of neuromuscular blockers required in patients who have imbibed significant amounts of alcohol.