Denervated Segments of Injured Skeletal Muscle Fibers Are Reinnervated by Newly Formed Neuromuscular Junctions

A muscle fiber normally receives its innervation at a single neuromuscular junction (NMJ). Transection of myofiber usually leaves one (abjunctional) stump denervated, while the other (adjunctional) remains innervated. To determine the mechanism of reinnervation of the abjunctional stumps, we transected the rat extensor digitorum muscle (EDL) below the site of the distalmost NMJ. Myofiber regeneration was followed for up to 56 days. Reinnervation began with the appearance of irregular acetylcholinesterase and alpha-bungarotoxin-positive deposits on abjunctional stumps after 10 to 15 days. These deposits later developed into more regular NMJ. The newly formed NMJ were innervated by sprouting axons which penetrated through the connective tissue scar separating the stumps. While denervated, the myofibers of the abjunctional segments underwent marked atrophy, which was reversed when reinnervation had ensued. In conclusion, we demonstrate for the first time that mature myofiber segments devoid of previous NMJ can induce both sprouting from intact axon terminals and formation of new "ectopic" NMJ on their own surface. This type of reinnervation is likely to occur only when myofibers are asymmetrically transected by a trauma. The signaling molecules possibly involved in this phenomenon are discussed.