MOTOR nerves have an important role in the trophic regulation of many properties of skeletal muscle, including acetylcholine receptor (AChR) distribution1. In innervated muscle, the density of AChR at neuromuscular junctions is at least 2,500 times greater than at extrajunctional regions2. When the motor nerves are sectioned, extrajunctional AChR density increases markedly2-5. The trophic mechanisms by which the nerves normally prevent this denervation change are not yet well understood. It has been suggested that muscle use contributes to the control of AChR. This hypothesis has been tested in two ways. First, electrical stimulation was applied directly to denervated muscle, and the extrajunctional ACh sensitivity was determined. The results indicated that stimulation-induced use largely prevented the denervation effect6,7. Second, attempts have been made to assess the effect of disuse of muscle on extrajunctional ACh sensitivity. Various methods have been used to eliminate muscle contraction but all have had shortcomings. In some cases, the 'disuse' has been incomplete8-10; in others, the methods used to block nerve conduction7,11 have produced blockade of axonal transport12,13, which may itself result in denervation effects14,15. Using a new model of disuse free of these problems, we have now compared the effects of disuse and denervation with respect to extrajunctional AChR density. We report here evidence that disuse produces a significant increase in extrajunctional AChR, but does not completely reproduce the effect of surgical denervation.
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