Dunant Y, Esquerda J E, Loctin F, Marsal J, Muller D
Département de Pharmacologie, Centre Médical Universitaire, Geneve, Switzerland.
J Physiol (Paris). 1990;84(3):211-9.
The physiological, morphological and biochemical effects of type A Botulinum toxin (BoTX) were analysed in the electric organ of Torpedo, a modified neuromuscular system. The quantal content of the postsynaptic potential, or electroplaque potential (EPP), was reduced by BoTX but the quantum size remained unchanged till complete failure of the neurally evoked transmission. BoTX also suppressed the occurrence of spontaneous electroplaque potentials (MEPPs) of a quantal size but potentials of a smaller amplitude still kept on occurring in the intoxicated synapses. BoTX inhibited the evoked release of acetylcholine (ACh; biochemically measured) but the rate of spontaneous ACh release transiently increased during the period when evoked release went down. On the other hand, there were no significant change of ACh content, of ACh turnover, of ACh repartition in the vesicular and free compartments, or in the number of synaptic vesicles. Surprisingly, the amount of ATP was reduced to 50% in BoTX treated tissue at the time of transmission failure; also the level of creatine phosphate (CrP) was lowered to less than 20% and the rate of activity of creatine kinase was reduced. It was concluded that, electrophysiologically, BoTX affects synaptic transmission in a very similar way in the electric organ and in the neuromuscular junctions. On the other hand, the shortage of ATP supply found in the present study may play a role in the pathophysiology of intoxication and should be taken into account in investigations designed to see whether BoTX affects various phosphorylations in cholinergic nerve terminals.
在电鳐的电器官（一种经过改良的神经肌肉系统）中分析了A型肉毒杆菌毒素（BoTX）的生理、形态和生化效应。BoTX可降低突触后电位或电板电位（EPP）的量子含量，但量子大小保持不变，直到神经诱发传递完全失效。BoTX还抑制了量子大小的自发电板电位（MEPPs）的出现，但在中毒的突触中仍会持续出现较小幅度的电位。BoTX抑制了乙酰胆碱（ACh；生化测量）的诱发释放，但在诱发释放下降期间，ACh的自发释放速率短暂增加。另一方面，ACh含量、ACh周转率、ACh在囊泡和游离部分的分配或突触小泡数量均无显著变化。令人惊讶的是，在传递失败时，BoTX处理的组织中ATP含量降至50%；肌酸磷酸（CrP）水平也降至20%以下，肌酸激酶的活性速率降低。得出的结论是，在电生理方面，BoTX在电器官和神经肌肉接头中以非常相似的方式影响突触传递。另一方面，本研究中发现的ATP供应短缺可能在中毒的病理生理学中起作用，并且在旨在观察BoTX是否影响胆碱能神经末梢各种磷酸化的研究中应予以考虑。
