The production of denervation-like changes in rat muscle by colchicine, without interference with axonal transport or muscle activity.

Abstract

1. Rat extensor digitorum longus (EDL) muscles were examined after colchicine treatment of the sciatic nerve. Colchicine was applied in one of two ways: (i) a single sub-epineural injection; (ii) a chronically implanted silicone cuff. 2. After the sub-epineural injection, the entire membrane of muscle fibres became sensitive to iontophoretically applied acetylcholine and the muscle action potentials became resistant to tetrodotoxin. However, the majority of these fibres were found to be normally innervated. 3. These effects were not restricted to the EDL muscle of the colchicine injected side but were also found in the EDL muscle of the contralateral side, indicating that the action of colchicine was systemic. 4. In the treated sciatic nerve there was a partial block of axonal transport of 3H-labelled proteins, which correlated with a partial paralysis of the ipsilateral leg. However, axoplasmic transport was found to be normal in the contralateral sciatic nerve and the contralateral limb was not paralysed despite the supersensitivity of the investigated muscle on that side. 5. When colchicine was applied with a silicone cuff, denervation-like changes were confined to the ipsilateral EDL muscle. However, impulse conduction block at the level of the cuff was usually observed. 6. It is concluded that (i) colchicine can produce denervation-like changes in normally active muscle without blocking axoplasmic transport, through an action probably exerted directly on the muscle membrane, and (ii) that colchicine-cuff experiments failed to provide unambiguous evidence in support of the existence of neurotrophic influences on the muscle membrane.