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Keywords:

  • botulinum neurotoxin;
  • SNAP-25;
  • acetylcholine release;
  • twitch tension;
  • end plate currents;
  • spontaneous release

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 hr.) 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 Ca2+ signals in Neuro 2a cells.

Discussion: These results demonstrate that 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. © 2013 Wiley Periodicals, Inc.