Hong S J, Lee S H, Chang C C
Department of Pharmacology, College of Medicine, National Taiwan University, Taipei.
Neuroscience. 1995 Jul;67(1):169-75. doi: 10.1016/0306-4522(95)00046-l.
Stimulation of mammalian motor neurons can elicit Ca(2+)-dependent regenerative release of acetylcholine and prolonged endplate depolarization when the enzymatic degradation of the neurotransmitter is inhibited. Unlike physiological phasic release of acetylcholine, the regenerative release is sensitive to L-type Ca2+ channel blockers. We studied the effects of vesamicol (an inhibitor of active transport of acetylcholine into synaptic vesicles) and omega-agatoxin IVA (a blocker of the motor nerve P-type Ca2+ channel) on these two types of acetylcholine release to compare the vesicle pools and Ca2+ channels responsible for the release. When coupled with repetitive stimulations, vesamicol decreased mean amplitude of miniature endplate potentials, resulting in a skewed distribution to lower amplitude, reduced quantal content of endplate potentials and decreased immediate available pool of acetylcholine. omega-Agatoxin IVA had no effect on miniature endplate potential but inhibited quantal content of endplate potential. The mean inhibitory concentration was around 5-10 nM. Vesamicol and omega-agatoxin IVA decreased the probability of triggering regenerative release. However, the magnitude and duration of regenerative release, once triggered, were not depressed by either agent. It appears that the majority of Ca2+ necessary for regenerative release is translocated via omega-agatoxin IVA-insensitive Ca2+ channels, which can be activated by prolonged depolarization of nerve terminals induced by accumulated acetylcholine. The results suggest that different Ca2+ channels are activated in the regenerative (L-type) and phasic (P-type) acetylcholine release, which utilize different pools of synaptic vesicles.
当神经递质的酶促降解受到抑制时，刺激哺乳动物运动神经元可引发钙离子（Ca(2+)）依赖性的乙酰胆碱再生性释放以及终板去极化延长。与乙酰胆碱的生理性相位释放不同，再生性释放对L型钙离子通道阻滞剂敏感。我们研究了vesamicol（一种抑制乙酰胆碱主动转运至突触小泡的抑制剂）和ω-芋螺毒素IVA（一种运动神经P型钙离子通道阻滞剂）对这两种类型乙酰胆碱释放的影响，以比较负责释放的小泡池和钙离子通道。当与重复刺激相结合时，vesamicol降低了微小终板电位的平均幅度，导致幅度分布偏向较低值，降低了终板电位的量子含量，并减少了乙酰胆碱的即时可用池。ω-芋螺毒素IVA对微小终板电位没有影响，但抑制了终板电位的量子含量。平均抑制浓度约为5 - 10 nM。Vesamicol和ω-芋螺毒素IVA降低了触发再生性释放的概率。然而，一旦触发，再生性释放的幅度和持续时间均未被这两种药物抑制。似乎再生性释放所需的大部分钙离子是通过对ω-芋螺毒素IVA不敏感的钙离子通道转运的，这些通道可被积累的乙酰胆碱诱导的神经末梢长时间去极化激活。结果表明，在再生性（L型）和相位性（P型）乙酰胆碱释放中激活了不同的钙离子通道，它们利用不同的突触小泡池。
