Acetylcholine receptors in regenerating muscle accumulate at original synaptic sites in the absence of the nerve.

TLDR

When muscle fibers are damaged, they degenerate and are phagocytized, but their basal lamina sheaths survive. We examined the role of nerve terminals in organizing acetylcholine receptors on regenerating skeletal‑muscle fibers. After denervating and damaging muscle, we allowed myofibers to regenerate while preventing reinnervation, and mapped acetylcholine receptor distribution using [125I] alpha‑bungarotoxin or HRP‑alpha‑bungarotoxin with cholinesterase staining of basal lamina synaptic sites. By one month after damage, new myofibers accumulate acetylcholine receptors selectively at the original synaptic sites with densities and junctional‑fold–like structures comparable to normal neuromuscular junctions, demonstrating that subsynaptic membrane organization is directed by residual synaptic structures independent of nerve terminals.

Abstract

We examined the role of nerve terminals in organizing acetylcholine receptors on regenerating skeletal-muscle fibers. When muscle fibers are damaged, they degenerate and are phagocytized, but their basal lamina sheaths survive. New myofibers form within the original basal lamina sheaths, and they become innervated precisely at the original synaptic sites on the sheaths. After denervating and damaging muscle, we allowed myofibers to regenerate but deliberately prevented reinnervation. The distribution of acetylcholine receptors on regenerating myofibers was determined by histological methods, using [125I] alpha-bungarotoxin or horseradish peroxidase-alpha-bungarotoxin; original synaptic sites on the basal lamina sheaths were marked by cholinesterase stain. By one month after damage to the muscle, the new myofibers have accumulations of acetylcholine receptors that are selectively localized to the original synaptic sites. The density of the receptors at these sites is the same as at normal neuromuscular junctions. Folds in the myofiber surface resembling junctional folds at normal neuromuscular junctions also occur at original synaptic sites in the absence of nerve terminals. Our results demonstrate that the biochemical and structural organization of the subsynaptic membrane in regenerating muscle is directed by structures that remain at synaptic sites after removal of the nerve.