Increasing evidence indicates that, first, the sympathetic nervous system interacts extensively with both vasculature and skeletal muscle fibers near neuromuscular junctions (NMJs) and, second, its neurotransmitter, noradrenaline, influences myofiber molecular composition and function and motor innervation. Since sympathomimetic agents have been reported to improve NMJ transmission, we examined whether two in clinical use, salbutamol and clenbuterol, affect the motor axon terminal via extracellular Ca2+ and molecular targets, such as TRPV1 and P/Q- and N-type voltage-activated Ca2+ channels. Electrophysiological recordings in ex-vivo preparations of peroneal nerves and lumbricalis muscles from young adult mice focused on spontaneous miniature end-plate potentials and singly and repetitively evoked end-plate potentials. Adding one dose of salbutamol or clenbuterol to the nerve/muscle preparation or repeatedly administering salbutamol to a mouse for 4 weeks increased spontaneous and evoked synaptic vesicle release but induced a steep decline in EPP amplitude in response to repetitive nerve stimulation. These effects were mediated primarily by ω-agatoxin IVA-sensitive P/Q-type and secondarily by ω-conotoxin GVIA-sensitive N-type Ca2+ channels. Presynaptic arvanil-sensitive TRPV1 channels seem to regulate Ca2+ at the motor neuron terminal at rest, while putative presynaptic β-adrenergic receptors may mediate sympathomimetic and catecholamine effects on presynaptic Ca2+ channels during NMJ activation.

中文翻译：

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拟交感神经药通过 TRPV1、P/Q- 和 N- 型 Ca2+ 通道调节神经肌肉接头传递。


越来越多的证据表明，首先，交感神经系统与神经肌肉接头 (NMJ) 附近的脉管系统和骨骼肌纤维广泛相互作用，其次，其神经递质去甲肾上腺素影响肌纤维的分子组成和功能以及运动神经支配。由于拟交感神经药已被报道可改善 NMJ 传播，我们检查了临床使用的两种药物（沙丁胺醇和克伦特罗）是否通过细胞外 Ca2+ 和分子靶标（如 TRPV1 和 P/Q- 和 N-型电压激活）影响运动轴突末端。 Ca2+ 通道。年轻成年小鼠的腓神经和蚓肌的离体制备中的电生理记录集中于自发微型终板电位以及单次和重复诱发的终板电位。在神经/肌肉制剂中添加一剂沙丁胺醇或克伦特罗，或对小鼠重复施用沙丁胺醇 4 周，可增加自发和诱发的突触小泡释放，但会导致响应重复神经刺激的 EPP 振幅急剧下降。这些效应主要由 ω- 雷蛇毒素 IVA 敏感的 P/Q 型通道介导，其次由 ω-芋螺毒素 GVIA 敏感的 N 型 Ca2+ 通道介导。突触前arvanil敏感的TRPV1通道似乎调节静止时运动神经元末端的Ca2+，而假定的突触前β-肾上腺素受体可能在NMJ激活期间介导对突触前Ca2+通道的拟交感神经和儿茶酚胺作用。