Skip to main content
SpringerLink
Log in

Alterations in the calcium homeostasis of skeletal muscle from postmyocardial infarcted rats

  • Skeletal Muscle
  • Published:
Pflügers Archiv - European Journal of Physiology Aims and scope Submit manuscript

Abstract

In chronic heart failure, skeletal muscles develop a weakness that is not associated to an impaired circulatory function but rather to alterations in the skeletal muscle fibers themselves. To understand these changes, the steps in excitation–contraction coupling of rats that underwent a left anterior coronary artery occlusion were studied. About 24 weeks after the myocardial infarction, neither the total amount nor the voltage dependence of intramembrane charge were altered. In contrast, calcium release from the sarcoplasmic reticulum was considerably suppressed, and its voltage dependence shifted toward more positive voltages. Elementary calcium-release events showed altered morphology as the relative proportion of embers increased. Calcium sparks were smaller in amplitude and had larger time-to-peak values. Isolated ryanodine receptors (RyR) displayed an unusual rectification with increased single-channel conductance at positive (cis vs trans) voltages. In addition, the bell-shaped calcium dependence of channel activity was broader, with a slight shift of activation to lower and a larger shift in inactivation to higher calcium concentrations. These data indicate that the number of channels that open during a calcium-release event is decreased and that RyR function is altered; thus, calcium-release is suppressed after a myocardial infarction. These observations give an explanation for the impaired skeletal muscle function in these animals.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5
Fig. 6
Fig. 7

Similar content being viewed by others

References

  1. Carter S, Colyer J, Sitsapesan R (2006) Maximum phosphorylation of the cardiac ryanodine receptor at serine-2809 by protein kinase a produces unique modifications to channel gating and conductance not observed at lower levels of phosphorylation. Circ Res 98:1506–1513

    Article  PubMed  CAS  Google Scholar 

  2. Cheng H, Song LS, Shirokova N, Gonzalez A, Lakatta EG, Rios E, Stern MD (1999) Amplitude distribution of calcium sparks in confocal images: theory and studies with an automatic detection method. Biophys J 76:606–617

    PubMed  CAS  Google Scholar 

  3. Clark AL, Poole-Wilson PA, Coats A (1996) Exercise limitation in chronic heart failure: central role of the periphery. J Am Coll Cardiol 28:1092–1102

    Article  PubMed  CAS  Google Scholar 

  4. Coats AJ (1996) The “muscle hypothesis” of chronic heart failure. J Mol Cell Cardiol 28:2255–2262

    Article  PubMed  CAS  Google Scholar 

  5. Cohn JN, Johnson GR, Shabetai R, Loeb H, Tristani F, Rector T, Smith R, Fletcher R (1993) Ejection fraction, peak exercise oxygen consumption, cardiothoracic ratio, ventricular arrhythmias, and plasma norepinephrine as determinants of prognosis in heart failure. The V-HeFT VA Cooperative Studies Group. Circulation 87:VI5–V16

    PubMed  CAS  Google Scholar 

  6. Csernoch L, Pizarro G, Uribe I, Rodriguez M, Rios E (1991) Interfering with calcium release suppresses I gamma, the “hump” component of intramembranous charge movement in skeletal muscle. J Gen Physiol 97:845–884

    Article  PubMed  CAS  Google Scholar 

  7. Csernoch L, Szentesi P, Sarkozi S, Szegedi Cs, Jona I, Kovacs L (1999) Effects of tetracaine on sarcoplasmic calcium release in mammalian skeletal muscle fibres. J Physiol 515:843–857

    Article  PubMed  CAS  Google Scholar 

  8. Delbono O, Chu A (1995) Ca2+ release channels in rat denervated skeletal muscle. Exp Physiol 80:561–574

    PubMed  CAS  Google Scholar 

  9. De Sousa E, Veksler V, Bigard X, Mateo P, Ventura-Clapier R (2000) Heart failure affects mitochondrial but not myofibrillar intrinsic properties of skeletal muscle. Circulation 102:1847–1853

    PubMed  Google Scholar 

  10. Fabiato A (1988) Computer programs for calculating total from specified free or free from specified total ionic concentrations in aqueous solutions containing multiple metals and ligands. Methods Enzymol 157:378–417

    Article  PubMed  CAS  Google Scholar 

  11. Hollingworth S, Peet J, Chandler WK, Baylor SM (2001) Calcium sparks in intact skeletal muscle fibers of the frog. J Gen Physiol 118:653–678

    Article  PubMed  CAS  Google Scholar 

  12. Jondeau G, Katz SD, Zohman L, Goldberger M, McCarthy M, Bourdarias J-P, LeJemtel TH (1992) Active skeletal muscle mass and cardiopulmonary reserve. Failure to attain peak aerobic capacity during maximal bicycle exercise in patients with severe congestive heart failure. Circulation 86:1351–1356

    PubMed  CAS  Google Scholar 

  13. Kirsch WG, Uttenweiler D, Fink RHA (2001) Spark- and ember-like elementary Ca2+ release events in skinned fibers of adult mammalian skeletal muscle. J Physiol 537:379–389

    Article  PubMed  CAS  Google Scholar 

  14. Klein MG, Lacampagne A, Schneider MF (1997) Voltage dependence of the pattern and frequency of discrete Ca2+ release events after brief repriming in frog skeletal muscle. Proc Natl Acad Sci USA 94:11061–11066

    Article  PubMed  CAS  Google Scholar 

  15. Kovács L, Rios E, Schneider MF (1983) Measurement and modification of free calcium transients in frog skeletal muscle fibres by a metallochromic indicator dye. J Physiol 343:161–196

    PubMed  Google Scholar 

  16. Lai FA, Meissner G (1990) Structure of the calcium release channel of skeletal muscle sarcoplasmic reticulum and its regulation by calcium. Adv Exp Med Biol 269:73–77

    PubMed  CAS  Google Scholar 

  17. Laver DR, Eager KR, Taoube L, Lamb GD (2000) Effects of cytoplasmic and luminal pH on Ca2+ release channels from rabbit skeletal muscle. Biophys J 78:1835–1851

    PubMed  CAS  Google Scholar 

  18. Lunde PK, Sejersted OM, Thorud HM, Tonnessen T, Henriksen UL, Christensen G, Westerblad H, Bruton J (2006) Effects of congestive heart failure on Ca2+ handling in skeletal muscle during fatigue. Circ Res 98:1514–1519

    Article  PubMed  CAS  Google Scholar 

  19. Lunde PK, Dahlstedt AJ, Bruton JD, Lannergren J, Thoren P, Sejersted OM, Westerblad H (2001) Contraction and intracellular Ca2+ handling in isolated skeletal muscle of rats with congestive heart failure. Circ Res 88:1299–1305

    Article  PubMed  CAS  Google Scholar 

  20. Lunde PK, Verburg E, Eriksen M, Sejersted OM (2002) Contractile properties of in situ perfused skeletal muscles from rats with congestive heart failure. J Physiol 540:571–580

    Article  PubMed  CAS  Google Scholar 

  21. Mancini D, LeJemtel T, Aaronson K (2000) Peak VO(2): a simple yet enduring standard. Circulation 101:1080–1082

    PubMed  CAS  Google Scholar 

  22. Marks AR (2002) Ryanodine receptors, FKBP12, and heart failure. Front Biosci 7:d970–d977

    Article  PubMed  CAS  Google Scholar 

  23. Marx SO, Ondrias K, Marks AR (1998) Coupled gating between individual muscle Ca2+ release channels (ryanodine receptors). Science 281:818–821

    Article  PubMed  CAS  Google Scholar 

  24. Massie BM, Conway M, Rajagopalan B, Yonge R, Frostick S, Ledingham J, Sleight P, Radda G (1988) Skeletal muscle metabolism during exercise under ischemic conditions in congestive heart failure. Evidence for abnormalities unrelated to blood flow. Circulation 78:320–326

    PubMed  CAS  Google Scholar 

  25. Melzer W, Rios E, Schneider MF (1986) The removal of myoplasmic free calcium following calcium release in frog skeletal muscle. J Physiol 372:261–292

    PubMed  CAS  Google Scholar 

  26. Mettauer B, Lampert E, Petitjean P, Bogui P, Epailly E, Schnedecker B, Geny BEB, Haberey P, Lonsdorfer J (1996) Persistent exercise intolerance following cardiac transplantation despite normal oxygen transport. Int J Sports Med 17:277–286

    Article  PubMed  CAS  Google Scholar 

  27. Mettauer B, Zoll J, Garnier A, Ventura-Clapier R (2006) Heart failure: a model of cardiac and skeletal muscle energetic failure. Pflugers Arch 452:653–666

    Article  PubMed  CAS  Google Scholar 

  28. Perreault CL, Gonzalez-Serratos H, Litwin SE, Sun X, Franzini-Armstrong C, Morgan JP (1993) Alterations in contractility and intracellular Ca2+ transients in isolated bundles of skeletal muscle fibers from rats with chronic heart failure. Circ Res 73:405–412

    PubMed  CAS  Google Scholar 

  29. Peters DG, Mitchell HL, McCune SA, Park S, Williams JH, Kandarian SC (1997) Skeletal muscle sarcoplasmic reticulum Ca2+-ATPase gene expression in congestive heart failure. Circ Res 81:703–710

    PubMed  CAS  Google Scholar 

  30. Poole-Wilson PA, Ferrari R (1996) Role of skeletal muscle in the syndrome of chronic heart failure. J Mol Cell Cardiol 28:2275–2285

    Article  PubMed  CAS  Google Scholar 

  31. Reiken S, Lacampagne A, Zhou H, Kherani A, Lehnart SE, Ward C, Huang F, Gaburjakova M, Gaburjakova J, Rosemblit N, Warren MS, He KL, Yi GH, Wang J, Burkhoff D, Vassort G, Marks AR (2003) PKA phosphorylation activates the calcium release channel (ryanodine receptor) in skeletal muscle: defective regulation in heart failure. J Cell Biol 160:919–928

    Article  PubMed  CAS  Google Scholar 

  32. Sabbah HN, Hansen-Smith F, Sharov VG, Kono T, Lesch M, Gengo PJ, Steffen RP, Levine TB, Goldstein S (1993) Decreased proportion of type I myofibers in skeletal muscle of dogs with chronic heart failure. Circulation 87:1729–1737

    PubMed  CAS  Google Scholar 

  33. Sarkozi S, Szentesi P, Jona I, Csernoch L (1996) Effects of cardiac glycosides on excitation–contraction coupling in frog skeletal muscle fibres. J Physiol 495:611–626

    PubMed  Google Scholar 

  34. Simonini A, Chang K, Yue P, Long CS, Massie BM (1999) Expression of skeletal muscle sarcoplasmic reticulum calcium-ATPase is reduced in rats with postinfarction heart failure. Heart 81:303–307

    PubMed  CAS  Google Scholar 

  35. Stratton JR, Kemp GJ, Daly RC, Yacoub M, Rajagopalan B (1994) Effects of cardiac transplantation on bioenergetic abnormalities of skeletal muscle in congestive heart failure. Circulation 89:1624–1631

    PubMed  CAS  Google Scholar 

  36. Sullivan MJ, Knight JD, Higginbotham MB, Cobb FR (1989) Relation between central and peripheral hemodynamics during exercise in patients with chronic heart failure. Muscle blood flow is reduced with maintenance of arterial perfusion pressure. Circulation 80:769–781

    PubMed  CAS  Google Scholar 

  37. Szentesi P, Jacquemond V, Kovacs L, Csernoch L (1997) Intramembrane charge movement and sarcoplasmic calcium release in enzymatically isolated mammalian skeletal muscle fibres. J Physiol 505:371–384

    Article  PubMed  CAS  Google Scholar 

  38. Szentesi P, Szappanos H, Szegedi C, Gonczi M, Jona I, Cseri J, Kovacs L, Csernoch L (2004) Altered elementary calcium release events and enhanced calcium release by thymol in rat skeletal muscle. Biophys J 86:1436–1453

    Article  PubMed  CAS  Google Scholar 

  39. Tripathy A, Meissner G (1996) Sarcoplasmic reticulum lumenal Ca2+ has access to cytosolic activation and inactivation sites of skeletal muscle Ca2+ release channel. Biophys J 70:2600–2615

    PubMed  CAS  Google Scholar 

  40. Wang Y, Xu L, Pasek DA, Gillespie D, Meissner G (2005) Probing the role of negatively charged amino acid residues in ion permeation of skeletal muscle ryanodine receptor. Biophys J 89:256–265

    Article  PubMed  CAS  Google Scholar 

  41. Ward CW, Reiken S, Marks AR, Marty I, Vassort G, Lacampagne A (2003) Defects in ryanodine receptor calcium release in skeletal muscle from post-myocardial infarct rats. FASEB J 17:1517–1519

    PubMed  CAS  Google Scholar 

  42. Williams JH, Ward CW (1998) Changes in skeletal muscle sarcoplasmic reticulum function and force production following myocardial infarction in rats. Exp Physiol 83:85–94

    PubMed  CAS  Google Scholar 

  43. Wilson JR, Groves J, Rayos G (1996) Circulatory status and response to cardiac rehabilitation in patients with heart failure. Circulation 94:1567–1572

    PubMed  CAS  Google Scholar 

  44. Zhou J, Brum G, Gonzalez A, Launikonis BS, Stern MD, Rios E (2003) Ca2+ sparks and embers of mammalian muscles. Properties of the sources. J Gen Physiol 122:95–114

    Article  PubMed  CAS  Google Scholar 

Download references

Acknowledgments

The authors are indebted for the excellent technical assistance from R. Öri. G.P. Szigeti holds a Bolyai Fellowship from the Hungarian Academy of Sciences. This work was supported by OTKA T049151, T61442 and NK61412. Guy Vassort held an INSERM position. He would like to thank A. Lacampagne for a very stimulating discussion.

Author information

Authors and Affiliations

  1. Department of Physiology, Medical and Health Science Center, University of Debrecen, P.O. Box 22, Debrecen, Hungary, 4012

    Gyula Péter Szigeti, János Almássy, Mónika Sztretye, Beatrix Dienes, László Szabó, Péter Szentesi, Sándor Sárközi, László Csernoch & István Jóna

  2. Department of Electrical Engineering, Sapientia Hungarian University of Transilvania, Targu Mures, Romania

    László Szabó

  3. INSERM U-637, Physiopathologie Cardiovasculaire, Université Montpellier1, Montpellier, France

    Guy Vassort

Authors
  1. Gyula Péter Szigeti
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. János Almássy
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Mónika Sztretye
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Beatrix Dienes
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. László Szabó
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Péter Szentesi
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Guy Vassort
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Sándor Sárközi
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. László Csernoch
    View author publications

    You can also search for this author in PubMed Google Scholar

  10. István Jóna
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to István Jóna.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Szigeti, G.P., Almássy, J., Sztretye, M. et al. Alterations in the calcium homeostasis of skeletal muscle from postmyocardial infarcted rats. Pflugers Arch - Eur J Physiol 455, 541–553 (2007). https://doi.org/10.1007/s00424-007-0298-z

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00424-007-0298-z

Keywords

Search

Navigation