Increased resistance to fatigue in creatine kinase deficient muscle is not due to improved contractile economy
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Abstract
There has been speculation on the origin of the increased endurance of skeletal muscles in creatine kinase (CK)-deficient mice. Important factors that have been raised include the documented increased mitochondrial capacity and alterations in myosin heavy chain (MyHC) isoform composition in CK-deficient muscle. More recently, the absence of inorganic phosphate release from phosphocreatine hydrolysis in exercising CK-deficient muscle has been postulated to contribute to the lower fatigueability in skeletal muscle. In this study, we tested the hypothesis that the reported shift in MyHC composition to slower isoforms in CK-deficient muscle leads to a decrease in oxygen cost of twitch performance. To that aim, extensor digitorum longus (EDL) and soleus (SOL) muscles were isolated from wild-type (WT) and knock-out mice deficient in the cytoplasmic muscle-type and sarcomeric mitochondrial isoenzymes of CK, and oxygen consumption per twitch time–tension-integral (TTI) was measured. The results show that the adaptive response to loss of CK function does not involve any major change to contractile economy of skeletal muscle.
Keywords
Contractile economy Transgenic mice Skeletal muscle Muscle fatigue Creatine kinaseAbbreviations
- CK
Creatine kinase
- Cr
Creatine
- EDL
Extensor digitorum longus
- PCr
Phosphocreatine
- SOL
Soleus
- MyHC
Myosin heavy chain
Notes
Acknowledgements
The authors wish to acknowledge Drs. B Wieringa, F Oerlemans, and K Steeghs (Nijmegen University) for supplying the transgenic mice. We thank Dr. RK Porter (Trinity College Dublin) who put an Oroboros oxygraph to our disposal. We are grateful to MJ Kushmerick and R Gronka for sharing Labview programs for analysis of the mechanics data, and A Doornenbal for expert help and further development of the force mechanics analysis. This research has been financially supported by The Council for Chemical Sciences of the Netherlands Organization for Scientific Research (CW-NWO).
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