Type A botulinum toxin disorganizes quantal acetylcholine release and inhibits energy metabolism.
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.
Dunant
Y
Y
Département de Pharmacologie, Centre Médical Universitaire, Geneve, Switzerland.
Esquerda
J E
JE
Loctin
F
F
Marsal
J
J
Muller
D
D
D000109:Acetylcholine / Q000032:analysis* / Q000378:metabolism; D000818:Animals; D001905:Botulinum Toxins / Q000494:pharmacology*; D004557:Electric Organ / Q000378:metabolism*; D004734:Energy Metabolism / Q000187:drug effects*; D005260:Female; D066298:In Vitro Techniques; D008297:Male; D013569:Synapses / Q000502:physiology; D009435:Synaptic Transmission / Q000187:drug effects; D014101:Torpedo
D001905:Botulinum Toxins; D000109:Acetylcholine