Effects of denervation and botulinum toxin on muscle sensitivity to acetylcholine and acceptance of foreign innervation in the frog.

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.