The action of caffeine in promoting ultrastructural damage in frog skeletal muscle fibres. Evidence for the involvement of the calcium-induced release of calcium from the sarcoplasmic reticulum.

1. Caffeine at concentrations above 5 mM was shown to cause rapidly extensive ultrastructural damage to the myofibrils of frog skeletal muscle. 2. The effect was promoted at lower temperatures, whereas the myofibrils were protected by prior exposure to procaine. 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. 4. Myofibril digradation 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. 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. 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.