Effects of botulinum toxin on synapse formation and acetylcholine sensitivity in skeletal muscle in the newt.

Abstract

A sublethal dose of botulinum toxin (type E) was injected into the biceps muscle of the forelimb of adult newts, Triturus cristatus, causing local paralysis for up to 3 weeks and impaired transmission for about 3 months. The paralysed muscles became supersensitive to the acetylcholine analogue, carbachol, and also accepted innervation from an implanted foreign nerve. These results suggest that in the newt activity is important in the control of muscle sensitivity to acetylcholine and synapse formation. During the first 2 months after botulinum toxin, stimulation of the implanted nerve caused contraction in every muscle examined (n = 13). In muscles examined between 3 and 14 months after toxin injection there was no contraction in response to stimulation of the implanted nerve in eight out of nineteen cases, suggesting that regression of the foreign innervation might have occurred. Further evidence for regression of foreign innervation was obtained by intracellular recordings from those muscles which contracted in response to stimulation of both nerves. The proportion of muscle fibres responding to stimulation of the implanted nerve fell significantly (P less than 0.05) from 65.7 +/- 7.1% (+/- S.E.M., n = 239) in thirteen muscles examined during the first 4 months to 39.5 +/- 5.5% (+/- S.E.M., n = 188) in nine muscles examined between 9 and 14 months after toxin injection. There was a strong negative correlation (r = 0.81; P less than 0.001) between the proportion of muscle fibres responding to stimulation of the original and implanted nerves in individual muscles.