Denervation-induced alterations of acetylcholinesterase in denervated and nondenervated muscle

Abstract

The influence of denervation on acetylcholinesterase (AchE) molecular forms in rat skeletal muscle for durations up to 30 days is examined in denervated anterior tibialis, the innervated contralateral muscle, and diaphragm. Denervated rats at a common age of 8.5 weeks are compared with age-matched, nondenervated animals. The results indicate that time-dependent losses of AchE in denervated muscle occur more rapidly than loss of muscle mass and are not uniform among the different molecular forms. Loss of the 4 S and 16 S forms is rapid and essentially complete within 3.5 days of denervation, while during this same period the 10.5 S form undergoes a transient twofold increase and its presence in denervated muscle is never abolished. Within 30 days of denervation, all forms of AchE including the 16 S species reappear. A salient finding of these studies is that the effects of denervation are evident also in anatomically remote, innervated muscle such as anterior tibialis of the contralateral limb and in diaphragm. These alterations appear as pronounced reductions in 4 S AchE and increases in 10.5 S AchE; the asymmetric collagen-tailed 16 S form is unaltered. Treatment of primary cultures of embryonic chick pectoral muscle with sera from denervated but not nondenervated rat causes reductions in AchE. These results indicate that the appearance and retention of AchE, in particular the 16 S form, occur in the absence of functional innervation. The effects of denervation on AchE metabolism in remote, innervated tissue are consistent with the action of a diffusible factor released from severed nerve or muscle, or both.