1. The effects of denervation and local paralysis produced by botulinum toxin (type D) on the sensitivity of skeletal muscle to ACh and its ability to accept innervation by an implanted foreign nerve were investigated in the frog. 2. Denervated muscles developed supersensitivity to ACh within 2 weeks and became extensively innervated by an implanted foreign nerve after about 4 weeks. 3. Chronic electrical stimulation of denervated muscles (50 Hz for 1 sec every 60 sec) did not prevent the development of supersensitivity. 4. Muscles paralysed by botulinum toxin did not usually develop supersensitivity to ACh until after 2‐3 months and the extra‐junctional sensitivity of individual fibres was generally less than after denervation. Significant innervation of the paralysed muscles by an implanted foreign nerve did not occur until after 2‐3 months. 5. The results suggest that in the frog nerves are able to control muscle sensitivity to ACh and to prevent innervation by foreign nerves by some mechanism other than muscle activity. Prolonged inactivity seems to result in some development of extra‐junctional sensitivity and acceptance of foreign innervation.
SUMMARYInjection of a sublethal dose of botulinum toxin (type D) into the cutaneus pectoris muscle of the frog caused paralysis for about three months, but in contrast to previous studies in the mammal, did not appear to cause axonal sprouting from motor nerve terminals. In frogs in which the cutaneus pectoris had been denervated by crushing its nerve, reinnervation occurred within 2-3 weeks and axonal sprouts beyond the original end-plates were often observed. When the hypoglossal nerve was implanted into the cutaneus pectoris, crushing the original nerve caused profuse axonal growth from the implanted nerve towards the denervated end-plates within one week, whereas injection of botulinum toxin had little effect. Stimulation of the implanted nerve caused contraction of those cutaneus pectoris muscles whose original nerves had been crushed, but no response to stimulation of the implanted nerve was seen in those muscles in which botulinum toxin had been injected. The failure of botulinum toxin to induce nerve sprouting and acceptance of foreign innervation in the frog may be due to the fact that activity may play a less important role in the neural control of the physiological properties of muscle in this species than in the mammal.
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