The Journal of Physiological Sciences

, Volume 60, Issue 5, pp 331–341 | Cite as

Phosphocreatine recovery overshoot after high intensity exercise in human skeletal muscle is associated with extensive muscle acidification and a significant decrease in phosphorylation potential

  • Jerzy A. ZoladzEmail author
  • Bernard Korzeniewski
  • Piotr Kulinowski
  • Justyna Zapart-Bukowska
  • Joanna Majerczak
  • Andrzej Jasiński
Original Paper


The phosphocreatine (PCr) recovery overshoot in skeletal muscle is a transient increase of PCr concentration above the resting level after termination of exercise. In the present study [PCr], [ATP], [Pi] and pH were measured in calf muscle during rest, during plantar flexion exercise until exhaustion and recovery, using the 31P NMR spectroscopy. A significantly greater acidification of muscle cells and significantly lower phosphorylation potential (ΔG ATP) at the end of exercise was encountered in the group of subjects that evidenced the [PCr] overshoot as well as [ADP] and [Pi] undershoots than in the group that did not. We postulate that the role of the PCr overshoot-related transiently elevated [ATP]/[ADPfree] ratio is to activate different processes (including protein synthesis) that participate in repairing numerous damages of the muscle cells caused by intensive exercise-induced stressing factors, such as extensive muscle acidification, a significant decrease in ΔG ATP, an elevated level of reactive oxygen species or mechanical disturbances.


31P NMR spectroscopy Acidosis Exercise Parallel activation PCr overshoot Skeletal muscle 



This study was supported by funding from the Polish Ministry of Science and Higher Education, grant no. N N404 196637. The authors thank Dr. Jacek Kibiński for his assistance during data collection.

Conflict of interest statement

There is no conflict of interest.


  1. 1.
    Greenhaff PL, Nevill ME, Söderlund K, Bodin K, Boobis LH, Williams C, Hultman E (1994) The metabolic responses of human type I and II muscle fibres during maximal treadmill sprinting. J Physiol 478:149–155PubMedGoogle Scholar
  2. 2.
    Harris RC, Hultman E, Nordesjo LO (1974) Glycogen, glycolytic intermediates and high-energy phosphates determined in biopsy samples of musculus quadriceps femoris of man at rest. Methods and variance of values. Scand J Clin Lab Invest 33:109–120PubMedGoogle Scholar
  3. 3.
    Harris RC, Edwards RH, Hultman E, Nordesjö LO, Nylind B, Sahlin K (1976) The time course of phosphorylcreatine resynthesis during recovery of the quadriceps muscle in man. Pflugers Arch 367:137–142CrossRefPubMedGoogle Scholar
  4. 4.
    Henriksson J, Sahlin K (2003) Metabolism during exercise-energy expenditure and hormonal changes. In: Kjaer M, Krogsgaard M, Magnusson P, Engebretsen L, Ross H, Takala T, Woo S (eds) Textbook of sports medicine: basic science and clinical aspects of sports injury and physical activity. Blackwell Science, OxfordGoogle Scholar
  5. 5.
    Sargeant AJ, De Haan A (2006) Human muscle fatigue: the significance of muscle fibre type variability studied using a micro-dissection approach. J Physiol Pharmacol 57:5–16PubMedGoogle Scholar
  6. 6.
    Kushmerick MJ, Meyer RA (1985) Chemical changes in rat leg muscle by phosphorus nuclear magnetic resonance. Am J Physiol 248:C542–C549PubMedGoogle Scholar
  7. 7.
    Söderlund K, Hultman E (1991) ATP and phosphocreatine changes in single human muscle fibres after intense electrical stimulation. Am J Physiol 261:E737–E741PubMedGoogle Scholar
  8. 8.
    Yoshida T, Watari H (1993) 31P-nuclear magnetic resonance spectroscopy study of the time course of energy metabolism during exercise and recovery. Eur J Appl Physiol Occup Physiol 66:494–499CrossRefPubMedGoogle Scholar
  9. 9.
    Christ M, Zange J, Janson CP, Müller K, Kuklinski P, Schmidt BM, Tillmann HC, Gerzer R, Wehling M (2001) Hypoxia modulates rapid effects of aldosterone on oxidative metabolism in human calf muscle. J Endocrinol Invest 24:587–597PubMedGoogle Scholar
  10. 10.
    Febbraio MA, Mckenna MJ, Snow RJ, Jenkins D, Hargreaves M (1995) Muscle metabolism during recovery from intermittent, maximal exercise. Proc Austr Physiol Pharmacol Soc 26:136PGoogle Scholar
  11. 11.
    Hargreaves M, Mckenna MJ, Jenkins DG, Warmington SA, Li JL, Snow RJ, Febbraio MA (1998) Muscle metabolites and performance during high-intensity, intermittent exercise. J Appl Physiol 84:1687–1691PubMedGoogle Scholar
  12. 12.
    Harris RC, Marlin DJ, Snow DH (1987) Metabolic response to maximal exercise of 800 and 2,000 m in the thoroughbred horse. J Appl Physiol 63:12–19PubMedGoogle Scholar
  13. 13.
    Kushmerick MJ, Meyer RA, Brown TR (1992) Regulation of oxygen consumption in fast- and slow-twitch muscle. Am J Physiol 263:C598–C606PubMedGoogle Scholar
  14. 14.
    Matheson GO, Allen PS, Ellinger DC, Hanstock CC, Gheorghiu D, Mckenzie DC, Stanley C, Parkhouse WS, Hochachka PW (1991) Skeletal muscle metabolism and work capacity: a 31P-NMR study of Andean natives and lowlanders. J Appl Physiol 70:1963–1976PubMedGoogle Scholar
  15. 15.
    Sahlin K, Söderlund K, Tonkonogi M, Hirakoba K (1997) Phosphocreatine content in single fibres of human muscle after sustained submaximal exercise. Am J Physiol 273:C172–C178PubMedGoogle Scholar
  16. 16.
    Tesch PA, Thorsson A, Fujitsuka N (1989) Creatine phosphate in fiber types of skeletal muscle before and after exhaustive exercise. J Appl Physiol 66:1756–1759PubMedGoogle Scholar
  17. 17.
    Korzeniewski B (2003) Regulation of oxidative phosphorylation in different muscles and various experimental conditions. Biochem J 375:799–804CrossRefPubMedGoogle Scholar
  18. 18.
    Korzeniewski B, Zoladz JA (2005) Some factors determining the PCr recovery overshoot in skeletal muscle. Biophys Chem 116:129–136CrossRefPubMedGoogle Scholar
  19. 19.
    Argov Z, De Stefano N, Arnold DL (1996) ADP recovery after a brief ischemic exercise in normal and diseased human muscle—a 31P-MRS study. NMR Biomed 9:165–172CrossRefPubMedGoogle Scholar
  20. 20.
    Kemp GJ, Roussel M, Bendahan D, Le Fur Y, Cozzone PJ (1998) The regulation of mitochondrial ATP synthesis in skeletal muscle during the transition from exercise to rest. In: Larsson C, Pahlman I, Gustaffson L (eds) BioThermoKinetics in the Postgenomic Era. Chalmers Reproservice, GöteborgGoogle Scholar
  21. 21.
    Wackerhage H, Hoffmann U, Essfeld D, Leyk D, Mueller K, Zange J (1998) Recovery of free ADP, Pi, and free energy of ATP hydrolysis in human skeletal muscle. J Appl Physiol 85:2140–2145PubMedGoogle Scholar
  22. 22.
    Korzeniewski B (1998) Regulation of ATP supply during muscle contraction: theoretical studies. Biochem J 330:1189–1195PubMedGoogle Scholar
  23. 23.
    Korzeniewski B (2007) Regulation of oxidative phosphorylation through parallel activation. Biophys Chem 129:93–110CrossRefPubMedGoogle Scholar
  24. 24.
    Korzeniewski B, Zoladz JA (2001) A model of oxidative phosphorylation in mammalian skeletal muscle. Biophys Chem 92:17–34CrossRefPubMedGoogle Scholar
  25. 25.
    Buttgereit F, Brand MD (1995) A hierarchy of ATP-consuming processes in mammalian cells. Biochem J 312:163–167PubMedGoogle Scholar
  26. 26.
    Naressi A, Couturier C, Devos JM, Janssen M, Mangeat C, De Beer R, Graveron-Demilly D (2001) Java-based graphical user interface for the MRUI quantitation package. MAGMA 12:141–152CrossRefPubMedGoogle Scholar
  27. 27.
    Cavassila S, Fenet A, Van Den Boogaart C, Remy C, Briguet C, Graveron-Demilly D (1997) ER-Filter: a preprocessing technique for frequency-selective time-domain analysis. J Magn Reson Anal 3:87–92Google Scholar
  28. 28.
    Vanhamme L, Van Den Boogaart A, Van Huffel S (1997) Improved method for accurate and efficient quantification of MRS data with use of prior knowledge. J Magn Reson 129:35–43CrossRefPubMedGoogle Scholar
  29. 29.
    Rossiter HB, Ward SA, Howe FA, Kowalchuk JM, Griffiths JR, Whipp BJ (2002) Dynamics of intramuscular 31P-MRS Pi peak splitting and the slow components of PCr and O2 uptake during exercise. J Appl Physiol 93:2059–2069PubMedGoogle Scholar
  30. 30.
    Greiner A, Esterhammer R, Bammer D, Messner H, Kremser C, Jaschke WR, Fraedrich G, Schocke MF (2007) High-energy phosphate metabolism in the calf muscle of healthy humans during incremental calf exercise with and without moderate cuff stenosis. Eur J Appl Physiol 99:519–531CrossRefPubMedGoogle Scholar
  31. 31.
    Esterhammer R, Schocke M, Gorny O, Posch L, Messner H, Jaschke W, Fraedrich G, Greiner A (2008) Phosphocreatine kinetics in the calf muscle of patients with bilateral symptomatic peripheral arterial disease during exhaustive incremental exercise. Mol Imaging Biol 10:30–39CrossRefPubMedGoogle Scholar
  32. 32.
    Francescato MP, Cettolo V, Di Prampero PE (2008) Influence of phosphagens concentrations on phosphocreatine breakdown kinetics. Data from human gastrocnemius muscle. J Appl Physiol 105:158–164CrossRefPubMedGoogle Scholar
  33. 33.
    Arnold DL, Matthews PM, Radda GK (1984) Metabolic recovery after exercise and the assessment of mitochondrial function in vivo in human skeletal muscle by means of 31P-NMR. Magn Reson Med 1:307–315CrossRefPubMedGoogle Scholar
  34. 34.
    Blei ML, Conley KE, Kushmerick MJ (1993) Separate measures of ATP utilization and recovery in human skeletal muscle. J Physiol 465:203–222PubMedGoogle Scholar
  35. 35.
    Kemp GJ, Roussel M, Bendahan D, Le Fur Y, Cozzone PJ (2001) Interrelations of ATP synthesis and proton handling in ischaemically exercising human forearm muscle studied by 31P magnetic resonance spectroscopy. J Physiol 15:901–928CrossRefGoogle Scholar
  36. 36.
    Iotti S, Frassineti C, Alderighi L, Sabatini A, Vacca A, Barbiroli B (2000) In vivo 31P-MRS assessment of cytosolic [Mg2+] in the human skeletal muscle in different metabolic conditions. Magn Reson Imaging 18:607–614CrossRefPubMedGoogle Scholar
  37. 37.
    Zoladz JA, Kulinowski P, Zapart-Bukowska J, Grandys M, Majerczak J, Korzeniewski B, Jasiński A (2007) Phosphorylation potential in the dominant leg is lower, and [ADPfree] is higher in calf muscles at rest in endurance athletes than in sprinters and in untrained subjects. J Physiol Pharmacol 58:803–819PubMedGoogle Scholar
  38. 38.
    Bessman SP, Geiger PJ (1981) Transport of energy in muscle: the phosphorylcreatine shuttle. Science 211:448–452CrossRefPubMedGoogle Scholar
  39. 39.
    Quistorff B, Johansen L, Sahlin K (1993) Absence of phosphocreatine resynthesis in human calf muscle during ischaemic recovery. Biochem J 291:681–686PubMedGoogle Scholar
  40. 40.
    Jubrias SA, Crowther GJ, Shankland EG, Gronka RK, Conley KE (2003) Acidosis inhibits oxidative phosphorylation in contracting human skeletal muscle in vivo. J Physiol 553:589–599CrossRefPubMedGoogle Scholar
  41. 41.
    Suleymanlar G, Zhou HZ, McCormack M, Elkins N, Kucera R, Reiss OK, Shapiro JI (1992) Mechanism of impaired energy metabolism during acidosis: role of oxidative metabolism. Am J Physiol 262:H1818–H1822PubMedGoogle Scholar
  42. 42.
    Westerblad H, Allen DG (1992) Myoplasmic free Mg2+ concentration during repetitive stimulation of single fibres from mouse skeletal muscle. J Physiol 453:413–434PubMedGoogle Scholar
  43. 43.
    Kemp GJ, Thompson CH, Sanderson AL, Radda GK (1994) pH control in rat skeletal muscle during exercise, recovery from exercise, and acute respiratory acidosis. Magn Reson Med 31:103–109CrossRefPubMedGoogle Scholar
  44. 44.
    Korzeniewski B, Zoladz JA (2003) Training-induced adaptation of oxidative phosphorylation in skeletal muscles. Biochem J 374:37–40CrossRefPubMedGoogle Scholar
  45. 45.
    Zoladz JA, Korzeniewski B, Grassi B (2006) Training-induced acceleration of oxygen uptake kinetics in skeletal muscle: the underlying mechanisms. J Physiol Pharmacol 57(Suppl 10):67–84PubMedGoogle Scholar
  46. 46.
    Bloch G, Chase JR, Avison MJ, Shulman RG (1993) In vivo 31P NMR measurement of glucose-6-phosphate in the rat muscle after exercise. Magn Reson Med 30:347–350CrossRefPubMedGoogle Scholar
  47. 47.
    Bendahan D, Confort-Gouny S, Kozak-Reiss G, Cozzone PJ (1990) Pi trapping in glycogenolytic pathway can explain transient Pi disappearance during recovery from muscular exercise. A 31P NMR study in the human. FEBS Lett 269:402–405CrossRefPubMedGoogle Scholar
  48. 48.
    Kikuchi K, Yamada T, Sugi H (2009) Effects of adrenaline on glycogenolysis in resting anaerobic frog muscles studied by 31P-NMR. J Physiol Sci 59:439–446CrossRefPubMedGoogle Scholar
  49. 49.
    Korzeniewski B, Liguzinski P (2004) Theoretical studies on the regulation of anaerobic glycolysis and its influence on oxidative phosphorylation in skeletal muscle. Biophys Chem 110:147–169CrossRefPubMedGoogle Scholar
  50. 50.
    Sargeant AJ, Dolan P (1987) Effect of prior exercise on maximal short-term power output in humans. J Appl Physiol 63:1475–1480PubMedGoogle Scholar
  51. 51.
    Sargeant AJ, Jones DA (1995) The significance of motor unit variability in sustaining mechanical output of muscle. Adv Exp Med Biol 384:323–338PubMedGoogle Scholar
  52. 52.
    Zoladz AJ, Rademaker ACHJ, Sargeant AJ (2000) Human muscle power generating capability during cycling at different pedaling rates. Exp Physiol 85:117–124CrossRefPubMedGoogle Scholar

Copyright information

© The Physiological Society of Japan and Springer 2010

Authors and Affiliations

  • Jerzy A. Zoladz
    • 1
    Email author
  • Bernard Korzeniewski
    • 2
  • Piotr Kulinowski
    • 3
  • Justyna Zapart-Bukowska
    • 1
  • Joanna Majerczak
    • 1
  • Andrzej Jasiński
    • 3
  1. 1.Department of Physiology and BiochemistryUniversity School of Physical Education-KrakówKrakowPoland
  2. 2.Faculty of Biochemistry, Biophysics and BiotechnologyJagiellonian UniversityKrakowPoland
  3. 3.Department of Nuclear RadiospectroscopyH. Niewodniczanski Institute of Nuclear PhysicsKrakowPoland

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