Sprouting of mammalian motor neurones at nodes of Ranvier: the role of the denervated motor endplate.

Treatment of the mouse gluteus maximus with the organophosphorus anticholinesterase ecothiopate, 4-aminopyridine and caffeine caused necrosis of the endplate region of the muscle fibres. When these drugs were given 12 h prior to partial denervation of the muscle there was a significant reduction in the amount of nodal sprouting seen 48 h after nerve section. No such reduction was seen if the drugs were given immediately after nerve section. In the former case both innervated and denervated fibres are necrotic; in the latter, only innervated fibres are necrotic. The amount of terminal sprouting was significantly increased in the former group, showing that the drug treatment and necrosis were not directly inhibitory to nerve growth. The reduction of nodal sprouting is therefore likely to be due to necrosis of denervated fibres; this supports the hypothesis that the denervated endplate is the source of a stimulus to nodal sprouting of motoneurones.