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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References
Axelsson, J., Thesleff, S.: Activation of the contractile mechanism in striated muscle. Acta Physiol. Scand. 44, 55–66 (1958)
Bittar, E. E., Hift, H., Huddart, H., Tong, E.: The effects of caffeine on sodium transport, membrane potential, mechanical tension and ultrastructure in barnacle muscle fibres. J. Physiol. (Lond.) 242, 1–34 (1974)
Carvalho, A. P.: Calcium-binding properties of sarcoplasmic reticulum as influenced by ATP, caffeine, quinine, and local anesthetics. J. Gen. Physiol. 52, 622–642 (1968)
Conway, D., Sakai, T.: Caffeine contracture. Proc. Natl. Acad. Sci. USA 46, 897–903 (1960)
Dayton, W. R., Goll, D. E., Zeece, M. G., Robson, R. M., Reville, W. J.: A Ca2+-activated protease possibly involved in myofibrillar protein turnover. Purification from porcine muscle. Biochemistry 15, 2150–2158 (1976a)
Dayton, W. R., Reville, W. J., Goll, D. E., Stromer, M. H.: A Ca2+-activated protease possibly involved in myofibrillar protein turnover. Partial characterization of the purified enzyme. Biochemistry 15, 2159–2167 (1976b)
Desmedt, J. E., Hainaut, K.: Inhibition of the intracellular release of calcium by dantrolene in barnacle giant muscle fibres. J. Physiol. (Lond.) 265, 565–585 (1977)
Duncan, C. J.: Role of intracellular calcium in promoting muscle damage: a strategy for controlling the dystrophic condition. Experientia (in press, 1978)
Ellis, K. O., Carpenter, J. F.: Studies on the mechanism of action of dantrolene sodium. Naunyn-Schmiedeberg's Arch. Pharmacol. 275, 83–94 (1972)
Endo, M.: Calcium release from the sacroplasmic reticulum. Physiol. Rev. 57, 71–108 (1977)
Endo, M., Tanaka, M., Ogawa, Y.: Calcium induced release of calcium from the sarcoplasmic reticulum of skinned skeletal muscle fibres. Nature (Lond.) 228, 34–36 (1970)
Feinstein, M. B.: Inhibition of caffeine rigor and radiocalcium movements by local anesthetics in frog sartorius muscle. J. Gen. Physiol. 47, 151–172 (1963)
Ford, L. E., Podolsky, R. J.: Regenerative calcium release within muscle cells. Science 167, 58–59 (1970)
Ford, L. E., Podolsky, R. J.: Calcium uptake and force development by skinned muscle fibres in EGTA buffered solutions. J. Physiol. (Lond.) 223, 1–19 (1972a)
Ford, L. E., Podolsky, R. J.: Intracellular calcium movements in skinned muscle fibres. J. Physiol. (Lond.) 223, 21–33 (1972b)
Gebert, G.: Caffeine contracture of frog skeletal muscle and of single muscle fibers. Am. J. Physiol. 215, 296–298 (1968)
Huddart, H., Oates, K.: Localization of the intracellular site of action of caffeine on skeletal muscle. Comp. Biochem. Physiol. 36, 677–682 (1970)
Iodice, A. A., Leong, V., Weinstock, I. M.: Separation of cathepsins A and D of skeletal muscle. Arch. Biochem. Biophys. 117, 477–486 (1966)
Karnovsky, M. J.: A formaldehyde-glutaraldehyde fixative of high osmolality for use in electron microscopy. J. Cell Biol. 27, 137A (1965)
Kohn, R. R.: A proteolytic system involving myofibrils and a soluble factor from normal and atrophying muscle. Lab. Invest. 20, 202–206 (1969)
Koszalka, T. R., Miller, L. L.: Proteolytic activity of rat skeletal muscle. I. Evidence for the existence of an enzyme active optimally at pH 8.5 to 9.0. J. Biol. Chem. 235, 665–668 (1960a)
Koszalka, T. R., Miller, L. L.: Proteolytic activity of rat skeletal muscle. II. Purification and properties of an enzyme active optimally at pH 8.5 to 9.0. J. Biol. Chem. 235, 669–672 (1960b)
Libby, P., Goldberg, A. L.: Leupeptin, a protease inhibitor, decreases protein degradation in normal and diseased muscles. Science 199, 534 (1978)
Lüttgau, H. C., Oetliker, H.: The action of caffeine on the activation of the contractile mechanism in striated muscle fibres. J. Physiol. (Lond.) 194, 51–74 (1968)
McGowan, E. B., Shafiq, S. A., Stracher, A.: Delayed degeneration of dystrophic and normal muscle cell cultures treated with pepstatin, leupeptin, and antipain. Exp. Neurol. 50, 649–657 (1976)
Ogawa, Y.: Some properties of frog fragmented sarcoplasmic reticulum with particular reference to its response to caffeine. J. Biochem. 67, 667–683 (1970)
Publicover, S. J., Duncan, C. J., Smith, J. L.: Ultrastructural changes in muscle mitochondria in situ, including the apparent development of internal septa, associated with the uptake and release of calcium. Cell Tiss. Res. 185, 373–385 (1977)
Publicover, S. J., Duncan, C. J., Smith, J. L.: The use of A23187 to demonstrate the role of intracellular calcium in causing ultrastructural damage in mammalian muscle. J. Neuropath. Exp. Neurol. 37, 544 (1978)
Reddy, M. K., Etlinger, J. D., Rabinowitz, M., Fischman, D. A., Zak, R.: Removal of Z-lines and α-actinin from isolated myofibrils by a calcium-activated neutral protease. J. Biol. Chem. 250, 4278–4284 (1975)
Reville, W. J., Goll, D. E., Stromer, M. H., Robson, R. M., Dayton, W. R.: A Ca2+-activated protease possibly involved in myofibrillar protein turnover—subcellular localisation of the protease in porcine skeletal muscle. J. Cell Biol. 70, 1–8 (1976)
Reynolds, E. S.: The use of lead citrate at high pH as an electronopaque stain in electron microscopy. J. Cell Biol. 17, 208–212 (1963)
Seiden, D.: Effects of colchicine on myofilament arrangement and the lysosomal system in skeletal muscle. Z. Zellforsch. 144, 467–473 (1973)
Spurr, A. R.: A low-viscosity epoxy resin embedding medium for electron microscopy. J. Ultrastruct. Res. 26, 31–43 (1969)
Statham, H. E., Duncan, C. J.: Dantrolene and the neuromuscular junction: evidence for intracellular calcium stores. Eur. J. Pharmacol. 39, 143–152 (1976)
Statham, H. E., Duncan, C. J., Smith, J. L.: The effect of the ionophore A23187 on the ultrastructure and electrophysiological properties of frog skeletal muscle. Cell Tiss. Res. 173, 193–209 (1976)
Taylor, S. R., Godt, R. E.: Calcium release and contraction in vertebrate skeletal muscle. In: Calcium in biological systems. Symp. Soc. exp. Biol. vol. 30 (C. J. Duncan, ed.), p. 361. Cambridge: University Press (1976)
Uhrik, B., Zacharova, D.: Recovery of ultrastructural changes accompanying caffeine contractures in isolated muscle fibres of the crayfish. Pflügers Arch. 364, 183–190 (1976)
Weber, A., Herz, R.: The relationship between caffeine contracture of intact muscle and the effect of caffeine on reticulum. J. Gen. Physiol. 52, 750–759 (1968)
Weber, A., Herz, R.: The relationship between caffeine contracture of intact muscle and the effect of caffeine on reticulum. J. Gen. Physiol. 52, 750–759 (1968)
Yamaguchi, T.: Caffeine-induced potentiation of twitches in frog single muscle fiber. Jap. J. Physiol. 25, 693–704 (1975)
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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