1. Acute and chronic effects of botulinum neurotoxin a on the mammalian neuromuscular junction.
- Author
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Baskaran P and Thyagarajan B
- Subjects
- 4-Aminopyridine analogs & derivatives, 4-Aminopyridine pharmacology, Acetylcholine metabolism, Acetylcholinesterase metabolism, Amifampridine, Animals, Calcium Ionophores pharmacology, Cell Line, Tumor, Electric Stimulation, Electromyography, In Vitro Techniques, Ionomycin pharmacology, Mice, Mice, Inbred C57BL, Neuroblastoma pathology, Neuromuscular Junction metabolism, Potassium Channel Blockers pharmacology, Reflex drug effects, Time Factors, Botulinum Toxins, Type A toxicity, Evoked Potentials, Motor drug effects, Neuromuscular Agents toxicity, Neuromuscular Junction drug effects
- Abstract
Introduction: Botulinum neurotoxin A (BoNT/A) cleaves SNAP-25 and inhibits acetylcholine (ACh) release at the neuromuscular junctions (NMJ) to cause neuroparalysis. Previous reports indicate a dyssynchrony between the inhibitory effect of BoNT/A on ACh release and SNAP-25 cleavage., Methods: We tested the in vitro (acute; 90 min) and in vivo (chronic; 12 h) effects of BoNT/A on stimulus-evoked ACh release (SEAR), twitch tension, and SNAP-25 cleavage in isolated extensor digitorum longus (EDL) nerve-muscle preparations (NMP)., Results: In vitro or in vivo BoNT/A poisoning inhibited SEAR and twitch tension. Conversely, SNAP-25 cleavage and inhibition of spontaneous release frequency were observed only in NMP poisoned with BoNT/A in vivo. Moreover, chronic treatment of BoNT/A inhibited ionomycin stimulated Ca(2+) signals in Neuro 2a cells., Conclusions: These results demonstrate that the inhibition of SEAR precedes SNAP-25 cleavage and suggest involvement of a more complex mechanism for the inhibitory effect of BoNT/A at the NMJ., (Copyright © 2013 Wiley Periodicals, Inc.)
- Published
- 2014
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