Botulinum toxin inhibits quantal acetylcholine release and energy metabolism in the Torpedo electric organ.
1. Type A Botulinum toxin (BoTX) blocked nerve-electroplaque transmission in small fragments of Torpedo marmorata electric organ incubated in vitro. The effect was observed either with the crystalline toxin complex (associated with haemagglutinin) or with the purified neurotoxin (molecular weight approximately 150,000). 2. The quantal content of the evoked post-synaptic response was reduced by BoTX but the quantum size remained unchanged till complete blockade of the evoked response. 3. Spontaneous electroplaque potentials were composed of two populations: one with a bell-shaped amplitude distribution (miniature potentials or quanta) and a population of small events with a skewed distribution (subminiatures). In BoTX-poisoned tissue, the bell-distributed miniatures progressively disappeared, but the subminiatures kept on occurring. Occasionally, larger spontaneous potentials with a slow time course were recorded; they were also BoTX resistant. 4. A biochemical assay showed that evoked acetylcholine (ACh) release was impaired by BoTX. During the period when evoked transmission was blocked, spontaneous ACh release transiently increased. 5. At the time of transmission blockade, there was no significant change of ACh content, of ACh turnover, of ACh repartition in the vesicle-bound and free compartments, or of the number of synaptic vesicles. 6. The amount of ATP was reduced to 50% by BoTX, and that of creatine phosphate (CrP) to less than 20%. The ATP-CrP-converting enzyme, creatine kinase, was inhibited in BoTX-poisoned tissue. 7. Thus, the electrophysiological effects of BoTX are very similar at the nerve-electroplaque and the neuromuscular junctions. The present work suggests in addition that suppression of quantal release by BoTX is related to marked alterations of the energy metabolism in the tissue.
Dunant
Y
Y
Département de Pharmacologie, Centre Médical Universitaire, Genève, Switzerland.
Esquerda
J E
JE
Loctin
F
F
Marsal
J
J
Muller
D
D
D000109:Acetylcholine / Q000378:metabolism*; D000200:Action Potentials / Q000187:drug effects; D000818:Animals; D001905:Botulinum Toxins / Q000494:pharmacology*; D004557:Electric Organ / Q000166:cytology / Q000378:metabolism*; D004734:Energy Metabolism / Q000187:drug effects*; D005260:Female; D066298:In Vitro Techniques; D008297:Male; D013572:Synaptic Vesicles / Q000648:ultrastructure; D014101:Torpedo / Q000502:physiology*
D001905:Botulinum Toxins; D000109:Acetylcholine