Independent pathways causing cellular damage in mouse soleus muscle under hypoxia.

1. Mouse soleus muscle incubated in vitro released creatine kinase (CK) and underwent ultrastructural damage under hypoxic conditions. 2. Both events were exacerbated by contractile activity following field stimulation. 3. Ultrastructural damage preceded CK release. 4. Omission of extracellular Ca2+ protected against CK release whereas ultrastructural damage was unaffected. 5. Excessive contractile activity for 30 min under normoxic conditions caused myofilament damage, but this was not accompanied by CK release. 6. The results support the hypothesis that the pathways leading to myofilament breakdown and to CK release are separate and independent. 7. The results are discussed in relation to changes in the supply of high energy phosphates and consequently in the regulation of Ca2+-homeostasis under hypoxia. 8. Both pathways are believed to be triggered by rises in [Ca2+]i. 9. A high rate of oxygenation (10 ml sec-1) had no damaging effects, unlike its action on mouse diaphragm in vitro. 10. Since damage is exacerbated under N2, there is no evidence to support the view that O2 metabolites are necessarily implicated in cell damage in skeletal muscle.