Loss and renewal of thick myofilaments in glucocorticoid-treated rat soleus after denervation and reinnervation.
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.
Massa
R
R
Department of Neurology-Neurosurgery, McGill University, Montreal, Quebec, Canada.
Carpenter
S
S
Holland
P
P
Karpati
G
G
D008841:Actin Cytoskeleton / Q000187:drug effects* / Q000473:pathology; D000818:Animals; D003907:Dexamethasone / Q000494:pharmacology*; D004591:Electrophoresis, Polyacrylamide Gel; D008297:Male; D008854:Microscopy, Electron; D009121:Muscle Denervation; D009132:Muscles / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D009416:Nerve Regeneration; D009929:Organ Size / Q000187:drug effects; D051381:Rats; D017207:Rats, Sprague-Dawley; D013643:Tarsus, Animal
D003907:Dexamethasone