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Decamethonium bromide-mediated inhibition of embryonic muscle development

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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.

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Acknowledgements

We thank F. Stockdale for the antibody samples S46 and F59. We also thank Mr. G. Frank, Mrs. S. Antoni, L. Koschny, and Mrs. E. Gimbel for their excellent technical assistance, and Mrs. C. Micucci for the photographic work. This study was supported by a grants from DAAD and Wellcome Trust (066195/Z/01/Z) to RM and a grant from the Deutsche Forschungsgemeinschaft (SFB 596, A1) to B.C.

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Authors and Affiliations

  1. Royal Veterinary College, Royal College Street, London, UK

    Raymond Macharia, Ketan Patel & Iain W. McKinnell

  2. Histopathology Unit, CRUK, London, UK

    William R. Otto

  3. Anatomisches Institut der Albert-Ludwigs-Universitat Freiburg, Albertstrasse 17, 79104, Freiburg, Germany

    Bodo Christ

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  1. Raymond Macharia
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  2. Ketan Patel
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  3. William R. Otto
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  4. Iain W. McKinnell
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  5. Bodo Christ
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Correspondence to Bodo Christ.

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Macharia, R., Patel, K., Otto, W.R. et al. Decamethonium bromide-mediated inhibition of embryonic muscle development. Anat Embryol 208, 75–85 (2004). https://doi.org/10.1007/s00429-003-0362-1

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  • DOI: https://doi.org/10.1007/s00429-003-0362-1

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