Priming the system that causes the release of cytosolic proteins in the perfused rat heart

Abstract

synergistically with caffeine to augment CK efflux markedly. Menadione and other quinones have cytotoxic effects in hepatocytes that are mediated via their one-electron reduction to semiquinone radicals which subsequently enter redox cycles with molecular oxygen to produce active oxygen species and oxidative stress. Alternatively, quinones may be reduced by a two-electron transfer to the more stable hydroquinone. There is no evidence for the involvement of oxygen metabolites in the mechanism underlying CK release in skeletal muscle which proceeds under N, [S], but menadione causes CK release (and myofilament damage [6]) and the process is again activated by the removal of extracellular Ca2 + , suggesting that (i) the same underlying biochemical pathway may operate in CK release triggered by caffeine and menadione; (ii) artificially generated 0, metabolites may be able to effect CK release; (iii) skeletal and cardiac muscles can be activated by the removal of extracellular Ca2+ and (iv) menadione does not act only by modifying Ca2+ channels and permitting Ca2+ entry (a suggested sequence for the events of the Ca2+ paradox of the rat heart [7]), since CK release is increased in the absence of extracellular Ca2+.