Is creatine kinase responsible for fatigue? Studies of isolated skeletal muscle deficient in creatine kinase

Abstract

Creatine kinase (CK) is a key enzyme for maintaining a constant ATP/ADP ratio during rapid energy turnover. To investigate the role of CK in skeletal muscle fatigue, we used isolated whole muscles and intact single fibers from CK-deficient mice (CK^−/−). With high-intensity electrical stimulation, single fibers from CK^−/− mice displayed a transient decrease in both tetanic free myoplasmic [Ca²⁺] ([Ca²⁺]_i, measured with the fluorescent dye indo-1) and force that was not observed in wild-type fibers. With less intense, repeated tetanic stimulation single fibers and EDL muscles, both of which are fast-twitch, fatigued more slowly in CK^−/− than in wild-type mice; on the other hand, the slow-twitch soleus muscle fatigued more rapidly in CK^−/− mice. In single wild-type fibers, tetanic force decreased and [Ca²⁺]_i increased during the first 10 fatiguing tetani, but this was not observed in CK^−/− fibers. Fatigue was not accompanied by phosphocreatine breakdown and accumulation of inorganic phosphate in CK^−/− muscles. In conclusion, CK is important for avoiding fatigue at the onset of high-intensity stimulation. However, during more prolonged stimulation, CK may contribute to the fatigue process by increasing the myoplasmic concentration of inorganic phosphate.—Dahlstedt, A. J., Katz, A., Wieringa, B., Westerblad, H. Is creatine kinase responsible for fatigue? Studies of isolated skeletal muscle deficient in creatine kinase.