Phospholipid distribution and stimulation of methylation during denervation and reinnervation in skeletal muscle

Denervation of the rat soleus and extensor digitorum longus muscles was induced by nerve crush. Functional signs of denervation were noted within 48 h with recovery beginning about the 12th day following denervation. There was also a marked decrease in muscle weight but only a small decrease in protein content per mg of muscle, subsequent to denervation. At 1, 2 and 3 weeks following nerve crush there was a relative decrease in muscle phosphatidylethanolamine (PE) and a corresponding increase in phosphatidylcholine (PC). The proportion of the other phospholipids did not significantly change. The levels of PC and PE returned to, or in some cases slightly overshot, control values at 4 and 5 weeks following nerve crush, i.e. during the period of reinnervation. Levels in non-denervated contralateral muscles did not significantly change. At 1 and 3 weeks following nerve crush a marked increase was observed in the activities of the enzymes PE-methyltransferases I and II, as measured by [(3)H]methyl group incorporation from S-adenosyl methionine into phosphatidylmonomethylethanolamine, phosphatidyldimethylethanolamine and PC. Increased activity of these methylases was seen in the contralateral control muscle, although less than in the denervated muscle. These enzymatic changes could be responsible for the changes in PE and PC distribution which we observed. Methylation of PE might also decrease the microviscosity of the membrane, thereby leading to other changes associated with denervation. Activation of this system might be another form of supersensitivity induced by denervation.