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Acute and chronic effects of botulinum neurotoxin a on the mammalian neuromuscular junction
Author(s) -
Baskaran Padmamalini,
Thyagarajan Baskaran
Publication year - 2014
Publication title -
muscle and nerve
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.025
H-Index - 145
eISSN - 1097-4598
pISSN - 0148-639X
DOI - 10.1002/mus.24119
Subject(s) - neuromuscular junction , acetylcholine , in vivo , inhibitory postsynaptic potential , in vitro , neurotoxin , chemistry , pharmacology , cleavage (geology) , neuromuscular transmission , biology , endocrinology , neuroscience , biochemistry , paleontology , microbiology and biotechnology , fracture (geology)
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. Muscle Nerve 50:206–215, 2014
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