Decamethonium bromide-mediated inhibition of embryonic muscle development.
This study determined the effect of decamethonium bromide (DMBr), a non-competitive blocker of the neuromuscular junction, on skeletal muscle development during chick embryogenesis. Decamethonium bromide caused generalized edema and high mortality with treated embryos rarely surviving beyond day 16 of incubation. Muscle degeneration was grossly evident on the muscles of abdomen, pectoral girdle, and leg. Semi-thin sections showed a high infiltration of macrophages in treated embryos and a massive degenerative process. Electron microscopy showed that both fast and slow fibers formed in the control and treated embryos, but those of the treated embryos failed to form myofibrils. Other organ systems, such as the heart and the gut, appeared histologically normal throughout the course of treatment. To investigate possible nerve independent action of DMBr on muscle development we determined the effect of this compound on the growth and differentiation of the C2C12 skeletal muscle cell line. DMBr treatment of C2C12 cell cultures did not affect the growth or survival of the cells, even at a tenfold higher concentration than that used in ovo, but myosin heavy chain expression was dramatically inhibited. We conclude that DMBr has a nerve independent blocking inhibition effect on myosin heavy chain synthesis in the developing avian embryo besides the recognized role as a non-competitive post-synaptic blocker of the neuromuscular junction.
Royal Veterinary College, Royal College Street, London, UK.
Raymond
R
Macharia
Ketan
K
Patel
William R
WR
Otto
Iain W
IW
McKinnell
Bodo
B
Christ
D000818:Animals; D002454:Cell Differentiation / Q000187:drug effects; D002455:Cell Division / Q000187:drug effects; D002460:Cell Line; D002642:Chick Embryo / Q000187:drug effects* / Q000378:metabolism / Q000502:physiology*; D003650:Decamethonium Compounds / Q000008:administration & dosage / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D018482:Muscle, Skeletal / Q000166:cytology / Q000196:embryology*; D009130:Muscle, Smooth / Q000196:embryology; D018995:Myosin Heavy Chains / Q000037:antagonists & inhibitors; D009467:Neuromuscular Depolarizing Agents / Q000008:administration & dosage / Q000494:pharmacology*
D003650:Decamethonium Compounds; D009467:Neuromuscular Depolarizing Agents; C033019:decamethonium; D018995:Myosin Heavy Chains