Cellular Damage in Mouse Skeletal Muscle Caused by Menadione

Abstract

Exposure of the isolated mouse soleus muscle preparation to 10, 25 or 50 µM menadione for 30 min causes subsequent release of creatine kinase (CK) and ultrastructural damage to the myofilament apparatus. CK release was slightly reduced under hypoxia (p M) were without significant effect. Mannitol at high concentration (50 mM) reduced CK efflux (p M) was approximately doubled when external Ca2+ was removed; under these conditions, hypoxia provided complete production. The ultrastructural damage of the myofilament apparatus and cell organelles was characteristic of that triggered by a raised [Ca2+]i and was unaffected by external conditions. It is concluded that (1) CK release and myofilament damage are independent pathways; (2) menadione causes the release of Ca2+ from intracellular sites and so causes cell damage; (3) O2 radicals do not play a major part in this Ca2+ release; (4) removal of extracellular Ca2+ activates the CK release mechanism and also switches it so that it operates via an O2-dependent mechanism, and (5) raised [Ca2+]i interacts synergistically with the activated CK release mechanism.