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Scientific article
English

Energy metabolism and quantal acetylcholine release: effects of botulinum toxin, 1-fluoro-2,4-dinitrobenzene, and diamide in the Torpedo electric organ

Published inJournal of neurochemistry, vol. 50, no. 2, p. 431-439
Publication date1988
Abstract

In the Torpedo electric organ, a modified nerve-muscle system, type A botulinum toxin blocked the release of acetylcholine (ACh) quanta, both neurally evoked and spontaneous. At the same time, the toxin increased the release of a class of small miniature potentials (the subminiature potentials), reduced the ATP and more the creatine phosphate content of the tissue, and impaired the activity of creatine kinase (CK). Thus, we compared this pattern of changes with those provoked by 1-fluoro-2,4-dinitrobenzene (FDNB), an efficient inhibitor of CK. As expected, FDNB rapidly inactivated CK, which resulted in a profound depletion of ATP whereas the stores of creatine phosphate were preserved. In addition, FDNB caused conspicuous morphological alterations of nerve endings and ACh depletion. This agent also suppressed evoked and spontaneous quantal release whereas the occurrence of subminature potentials was markedly increased. Diamide, a penetrating thiol oxidizing substance, provoked first a transient rise in quantal ACh release and then blockade of transmission with, again, production of a large number of subminiature potentials. Creatine phosphate was depleted in the tissue by diamide, the ATP content reduced, and CK activity partly inhibited. The morphology of nerve terminals did not show obvious changes with either diamide or botulinum toxin at the stage of transmission failure. Although the three poisons acted by different mechanisms, this resulted in a rather similar pattern of physiological changes: failure of quantal release and enhancement of subquantal release. These results and experiments on synaptosomes indicated that CK inhibition was probably a crucial mechanism for FDNB but not for diamide or botulinum intoxication.

Keywords
  • Acetylcholine/ secretion
  • Action Potentials/drug effects
  • Adenosine Triphosphate/metabolism
  • Animals
  • Botulinum Toxins/ pharmacology
  • Calcimycin/pharmacology
  • Creatine Kinase/metabolism
  • Diamide/pharmacology
  • Dinitrofluorobenzene/pharmacology
  • Electric Organ/drug effects/ metabolism/ultrastructure
  • Electrophysiology
  • Energy Metabolism/ drug effects
  • Microscopy, Electron
  • Synaptosomes/drug effects/metabolism
  • Torpedo/ metabolism
Citation (ISO format)
DUNANT, Yves et al. Energy metabolism and quantal acetylcholine release: effects of botulinum toxin, 1-fluoro-2,4-dinitrobenzene, and diamide in the Torpedo electric organ. In: Journal of neurochemistry, 1988, vol. 50, n° 2, p. 431–439. doi: 10.1111/j.1471-4159.1988.tb02930.x
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ISSN of the journal0022-3042
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