Pflügers Archiv

, Volume 452, Issue 3, pp 342–348 | Cite as

Increased resistance to fatigue in creatine kinase deficient muscle is not due to improved contractile economy

  • Frank ter Veld
  • Klaas Nicolay
  • Jeroen A.L. Jeneson
Skeletal Muscle

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 kinase 

Abbreviations

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).

References

  1. 1.
    Wallimann T, Wyss M, Brdiczka D, Nicolay K, Eppenberger HM (1992) Intracellular compartmentation, structure and function of creatine kinase isoenzymes in tissues with high and fluctuating energy demands: the ‘phosphocreatine circuit’ for cellular energy homeostasis. Biochem J 281:21–40PubMedGoogle Scholar
  2. 2.
    Steeghs K, Oerlemans F, de Haan A, Heerschap A, Verdoodt L, de Bie M, Ruitenbeek W, Benders A, Jost C, van Deursen J, Tullson P, Terjung R, Jap P, Jacob W, Pette D, Wieringa B (1998) Cytoarchitectural and metabolic adaptations in muscles with mitochondrial and cytosolic creatine kinase deficiencies. Mol Cell Biochem 184:183–194CrossRefPubMedGoogle Scholar
  3. 3.
    Dahlstedt AJ, Katz A, Wieringa B, Westerblad H (2000) Is creatine kinase responsible for fatigue? Studies of isolated skeletal muscle deficient in creatine kinase. Faseb J 14:982–990PubMedGoogle Scholar
  4. 4.
    Dahlstedt AJ, Katz A, Westerblad H (2001) Role of myoplasmic phosphate in contractile function of skeletal muscle: studies on creatine kinase-deficient mice. J Physiol 533:79–388CrossRefPubMedGoogle Scholar
  5. 5.
    Steeghs K, Benders A, Oerlemans F, de Haan A, Heerschap A, Ruitenbeek W, Jost C, van Deursen J, Perryman B, Pette D, Bruckwilder M, Koudijs J, Jap P, Veerkamp, J Wieringa B (1997) Altered Ca2+ responses in muscles with combined mitochondrial and cytosolic creatine kinase deficiencies. Cell 89:93–103CrossRefPubMedGoogle Scholar
  6. 6.
    Veksler VI, Kuznetsov AV, Anflous K, Mateo P, van Deursen J, Wieringa B, Ventura-Clapier R (1995) Muscle creatine kinase-deficient mice: II. Cardiac and skeletal muscles exhibit tissue-specific adaptation of the mitochondrial function. J Biol Chem 270:19921–19929CrossRefPubMedGoogle Scholar
  7. 7.
    Foley JM, Adams GR, Meyer RA (1994) Different effects of gradual vs. acute adenine nucleotide depletion on ATP cost of muscle contraction. Am J Physiol 267:1177–1184Google Scholar
  8. 8.
    Moerland TS, Kushmerick MJ (1994) Contractile economy and aerobic recovery metabolism in skeletal muscle adapted to creatine depletion. Am J Physiol 267:127–137Google Scholar
  9. 9.
    Steeghs K, Heerschap A, de Haan A, Ruitenbeek W, Oerlemans F, van Deursen J, Perryman B, Pette D, Bruckwilder M, Koudijs J, Jap P, Wieringa B (1997) Use of gene targeting for compromising energy homeostasis in neuro-muscular tissues: the role of sarcomeric mitochondrial creatine kinase. J Neurosci Methods 71:29–41PubMedCrossRefGoogle Scholar
  10. 10.
    van Deursen J, Heerschap A, Oerlemans F, Ruitenbeek W, Jap P, ter Laak H, Wieringa B (1993) Skeletal muscles of mice deficient in muscle creatine kinase lack burst activity. Cell 74:621–631CrossRefPubMedGoogle Scholar
  11. 11.
    ter Veld F (2003) Creatine kinase deficiency in striated mouse muscle: biochemical and physiological studies. Ph.D. thesis, Utrecht UniversityGoogle Scholar
  12. 12.
    Syme DA (1994) The efficiency of frog ventricular muscle. J Exp Biol 197:143–164PubMedGoogle Scholar
  13. 13.
    Haller T, Ortner M, Gnaiger E (1994) A respirometer for investigating oxidative cell metabolism: toward optimization of respiratory studies. Anal Biochem 218:338–442CrossRefPubMedGoogle Scholar
  14. 14.
    Crow MT, Kushmerick MJ (1982) Chemical energetics of slow- and fast-twitch muscles of the mouse. J Gen Physiol 79:147–166CrossRefPubMedGoogle Scholar
  15. 15.
    Moerland TS, Wolf NG, Kushmerick MJ (1989) Administration of a creatine analogue induces isomyosin transitions in muscle. Am J Physiol 257:810–816Google Scholar
  16. 16.
    Ren JM, Ohira Y, Holloszy JO, Hamalainen N, Traub I, Pette D (1995) Effects of beta-guanidinopropionic acid-feeding on the patterns of myosin isoforms in rat fast-twitch muscle. Pflugers Arch 430:389–393CrossRefPubMedGoogle Scholar
  17. 17.
    Shoubridge EA, Challiss RA, Hayes DJ, Radda GK (1985) Biochemical adaptation in the skeletal muscle of rats depleted of creatine with the substrate analogue beta-guanidinopropionic acid. Biochem J 232:125–131PubMedGoogle Scholar
  18. 18.
    de Groof AJ, Oerlemans FT, Jost CR, Wieringa B (2001) Changes in glycolytic network and mitochondrial design in creatine kinase-deficient muscles. Muscle Nerve 24:1188–1196CrossRefPubMedGoogle Scholar
  19. 19.
    Bottinelli R, Canepari M, Reggiani C, Stienen GJ (1994) Myofibrillar ATPase activity during isometric contraction and isomyosin composition in rat single skinned muscle fibres. J Physiol 481:663–675PubMedGoogle Scholar
  20. 20.
    Sweeney HL, Kushmerick MJ, Mabuchi K, Sreter FA, Gergely J (1988) Myosin alkali light chain and heavy chain variations correlate with altered shortening velocity of isolated skeletal muscle fibers. J Biol Chem 263:9034–9039PubMedGoogle Scholar
  21. 21.
    Homsher E, Mommaerts WF, Ricchiuti NV, Wallner A (1972) Activation heat, activation metabolism and tension-related heat in frog semitendinosus muscles. J Physiol 220:601–625PubMedGoogle Scholar
  22. 22.
    Gorselink M (2001) The development of an experimental model to assess mechanical performance of skeletal muscle in the intact mouse. University Maastricht, p 113Google Scholar
  23. 23.
    Agbulut O, Noirez P, Beaumont F, Butler-Browne G (2003) Myosin heavy chain isoforms in postnatal muscle development of mice. Biol Cell 95:399–406CrossRefPubMedGoogle Scholar
  24. 24.
    Sweeney HL (1994) The importance of the creatine kinase reaction: the concept of metabolic capacitance. Med Sci Sports Exerc 26:30–36PubMedGoogle Scholar
  25. 25.
    O’Gorman E, Beutner G, Wallimann T, Brdiczka D (1996) Differential effects of creatine depletion on the regulation of enzyme activities and on creatine-stimulated mitochondrial respiration in skeletal muscle, heart, and brain. Biochim Biophys Acta 1276:161–170PubMedCrossRefGoogle Scholar

Copyright information

© Springer-Verlag 2006

Authors and Affiliations

  • Frank ter Veld
    • 1
    • 4
  • Klaas Nicolay
    • 1
    • 2
  • Jeroen A.L. Jeneson
    • 2
    • 3
  1. 1.Department of Experimental In Vivo NMR, Image Sciences InstituteUniversity Medical Center UtrechtUtrechtThe Netherlands
  2. 2.Biomedical NMR, Department of Biomedical EngineeringEindhoven University of TechnologyEindhovenThe Netherlands
  3. 3.Department of Pathobiology, Division of Anatomy and Physiology, School of Veterinary MedicineUtrecht UniversityUtrechtThe Netherlands
  4. 4.German Diabetes CenterDüsseldorfGermany

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