Summary
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1.
Caffeine at concentrations above 5 mM was shown to cause rapidly extensive ultrastructural damage to the myofibrils of frog skeletal muscle.
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2.
The effect was promoted at lower temperatures, whereas the myofibrils were protected by prior exposure to procaine.
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3.
It is argued that caffeine causes a Ca2+-induced release of Ca2+ (the CROC) from the S.R. and that the consequent rise in [Ca2+]i promotes the ultrastructural damage observed.
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4.
Myofibril degradation is also produced by treatment of the muscle with the divalent cation ionophore A23187; this effect is not protected by either procaine or Dantrolene sodium.
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5.
It is suggested that A23187 causes the release of Ca2+ from the S.R. by a mechanism that differs from both excitation and the CROC; the resultant rise in [Ca2+]i again causes myofibril degradation.
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6.
The ways in which a marked rise in [Ca2+]i could cause muscle damage and the possible relevance of these findings to the sequence of events in the development of myopathies of human skeletal muscle are discussed.
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Duncan, C.J., Smith, J.L. The action of caffeine in promoting ultrastructural damage in frog skeletal muscle fibres. Naunyn-Schmiedeberg's Arch. Pharmacol. 305, 159–166 (1978). https://doi.org/10.1007/BF00508287
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DOI: https://doi.org/10.1007/BF00508287