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Keywords:

  • corticosteroids;
  • denervation;
  • reinnervation;
  • myosin;
  • thick myofilaments;
  • rat soleus muscle;
  • proteolysis

Abstract

Denervation of rat soleus muscle and simultaneous administration of high doses of corticosteroids for 7 days caused marked muscle fiber atrophy and selective loss of thick myofilaments from many muscle fibers by light and electron microscopy. Myosin heavy chain/ actin ratios were greatly reduced on polyacrylamide gel electrophoresis. Nerve crush instead of cut permitted reinnervation after 2 weeks and demonstrated the reversibility of the muscle changes within a week after reinnervation. There was formation of new thick filaments and their reintegration into myofibrils without further breakdown, although large areas of Z-disc streaming appeared. The mechanism of A-band breakdown remains obscure, but it presumably starts with limited proteolysis and continues with disaggregation of myosin molecules. This is consistent with our observation that the muscle fibers retain a relatively good reactivity to antibodies against myosin heavy chain 1 week after denervation and corticosteroid administration. A syndrome recalling these experiments is seen in severely asthmatic patients receiving corticosteroids and pharmacologically paralyzed for mechanical respiration. © 1992 John Wiley & Sons, Inc.