Is creatine kinase responsible for fatigue? Studies of isolated skeletal muscle deficient in creatine kinase.
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 [Ca(2+)] ([Ca(2+)](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 [Ca(2+)](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
AJ
Department of Physiology and Pharmacology, Karolinska Institutet, S-171 77 Stockholm, Sweden.
Katz
A
A
Wieringa
B
B
Westerblad
H
H
D000818:Animals; D003402:Creatine Kinase / Q000235:genetics / Q000378:metabolism*; D004558:Electric Stimulation; D066298:In Vitro Techniques; D051379:Mice; D018345:Mice, Knockout; D018763:Muscle Fatigue; D018482:Muscle, Skeletal / Q000201:enzymology* / Q000378:metabolism / Q000502:physiology; D013746:Tetany
D003402:Creatine Kinase