Decamethonium bromide-mediated inhibition of embryonic muscle development

Abstract

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.

Lymph heart in chick - somitic origin, development and embryonic oedema

“…These embryos displayed gross oedema from E8 and by E10 this was severe (Fig. 4F) and accentuated by degenerated oedematous skeletal muscles (Macharia et al, 2004). The character of the oedema was otherwise similar to the models above.…”

“…Decamethonium-induced immobility was complete for both the body and the lymph heart musculature and resulted in gross oedema formation (our observations) (Macharia et al, 2004; Hosseini and 4433 RESEARCH ARTICLE Lethal embryonic oedema Sullivan, 1966). By contrast, pancuronium, which also paralysed the body musculature, left the lymph hearts contracting (although more slowly) and oedema did not form.…”

“…All the oedemas of immobility were ascribed to the absence of lymph propulsion or decreased venous return, features dependent on skeletal muscle contractions (Macharia et al, 2004). The following considerations enable us to challenge this notion and ascribe a novel role for the lymph heart.…”

Mesenchymal and mechanical mechanisms of secondary cartilage induction

“…Decamethonium bromide is an agonist for the acetylcholine receptor on the post-synaptic membrane of the neuromuscular junction (Drachman, 1971). Exposure to decamethonium bromide produces a depolarizing cascade that blocks synaptic transmission in skeletal muscle but does not interfere with cardiac or smooth muscle contraction (Macharia et al, 2004). Solution was dispersed into the albumin over the developing embryo.…”

Use of Zebrafish ( Danio rerio ) Embryos as a Model to Assess Effects of Mercury on Developing Skeletal Muscle: A Morphometric and Immunohistochemical Study

“…These morphologic abnormalities suggest that myofibrils may be undergoing degeneration. In a research model looking at skeletal muscle development in chick embryos, exposure to decamethonium bromide resulted in muscle degeneration characterized by reduced or missing myofibrils as well as significantly decreased myosin protein expression (Macharia et al, 2004). Decreased staining of myosin in myofibrils also may be due to a slower or delayed rate of myosin development.…”