Basic Research in Cardiology

, Volume 84, Issue 6, pp 591–596 | Cite as

Glutathione alters calcium responsiveness of cardiac skinned fibers

  • S. F. Bauer
  • K. Schwarz
  • J. C. Rüegg
Original Contributions


The glutathione status of cardiac muscle, that is the ratio of reduced glutathione (GSH) to oxidized glutathione (GSSG) changes in certain forms of cardiomyopathy and during reperfusion of ischemic heart. Here we show that it also affects the sensitivity of contractile proteins to calcium. GSH (4 mM) increased the pCa50 for force development in skinned fibers by 0.2 pCa units and increased force ba 44%±5.4% at pCa 5.6 whereas GSSG (4 mM) decreased it by 54%±17.8% at pCa 5.6. Half maximal activations and inhibitions were seen with 4 mM GSH or GSSG, respectively.

In contrast to GSH, the reducing agent dithiotreitol at 5 mM had no activating effect. Our results suggest that the loss of contractility observed after a reperfusion of the ischemic heart my, at least in part, be due to a decreased responsiveness of the contractile proteins due to an altered glutathione status.

Key words

glutathione skinnedcardiac fiber oxidative stress calcium regulation 


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


  1. 1.
    Balentine JD (1982) Pathology of oxygen toxicity. Academic Press, New York LondonGoogle Scholar
  2. 2.
    Bindoli A, Cavallini L, Rigobello MP, Coassin M, Di Lisa F (1988) Modification of the xanthine converting enzyme of perfused rat heart during ischemia and oxidative stress. Free Radic Biol Med 4:163–167PubMedGoogle Scholar
  3. 3.
    Braughler JM (1988) Calcium and lipid peroxydation. In: Halliwell B (ed) Oxygen radicals and tissue injury. Fed Am Soc Exper Biol, pp 99–106Google Scholar
  4. 4.
    Burton KP (1988) Evidence of direct toxic effects of free radicals on the myocardium. Free Radic Biol Med 4:15–24PubMedGoogle Scholar
  5. 5.
    Ceconi C, Curello S, Cargnioni A, Ferrari R, Albertini A, Visioli O (1988) The role of glutathione status in the protection against ischemic and reperfusion damage: Effects of N-acetyl cysteine. J Mol Cell Cardiol 20:5–13PubMedGoogle Scholar
  6. 6.
    Crompton M, Costi A, Hayat L (1987) Evidence for the presence of a reversible Ca2+-dependent pore activated by oxidative stress in heart mitochondria. Biochem J 245:915–918PubMedGoogle Scholar
  7. 7.
    Curello S, Ceconi C, Bigoli B, Ferrari R, Albertini A, Guarnieri C (1985) Changes in the cardiac glutathione status after ischemia and reperfusion. Experienta 41:42–43Google Scholar
  8. 8.
    Das DK, Engelman RM, Flansaas D, Otani H, Rousou J, Breyer RH (1987) Developmental profiles of protective mechanisms of heart against peroxidative injury. Basic Res Cardiol 82:36–50PubMedGoogle Scholar
  9. 9.
    Doroshow JH, Locker GY, Myers CE (1980) Enzymatic defenses of the mouse heart against reactive oxygen metabolites. J Clin Invest 65:128–135PubMedGoogle Scholar
  10. 10.
    Elz JS, Nayler WG (1988) Contractile activity and reperfusion-induced calcium gain after ischemia in the isolated rat heart. Lab invest 58:653–659PubMedGoogle Scholar
  11. 11.
    Fabiato A, Fabiato F (1979) Calculator program for computing the composition of the solutions containing multiple metals and ligands used for experiments in skinned muscle cells. Journal de Physiologic 75:463–505Google Scholar
  12. 12.
    Fabiato A (1981) Myoplasmic free calcium concentrations reached during the twitch of an intact isolated cardiac cell and during calcium-induced release of calcium from the sarcoplasmatic reticulum of a skinned cardiac cell from the adult rat or rabbit ventricle. J Gen Physiol 78:457–497PubMedGoogle Scholar
  13. 13.
    Ferrari R, Ceconi C, Curello S, Guarnicri C, Caldarera CM, Albertini A, Visioli O (1985) Oxygen-mediated myocardial damage during ischemia and reperfusion: Role of the cellular defences against oxygen toxicity. J Mol Cell Cardiol 17:937–945PubMedGoogle Scholar
  14. 14.
    Galler S, Hutzler C (1988) Effects of free amino acids on tension generation by crustean skinned muscle fibers. Pflügers Arch 412:R82 (suppl)Google Scholar
  15. 15.
    Gauduel Y, Duvelleroy MA (1984) Role of oxygen radicals in cardiac injury due to reoxygenation. J Mol Cell Cardiol 16:459–470PubMedGoogle Scholar
  16. 16.
    Harrison S, Lamont Ch, Miller DJ (1986) Carnosine and other natural imidazoles enhance muscle Ca sensitivity and are mimicked by caffeine and AR-L 115BS. J Physiol 371:197PGoogle Scholar
  17. 17.
    Ishikawa T, Sies H (1984) Cardiac transport of glutathione disulfide and s-conjugate. J Biol Chem 259:3838–3843PubMedGoogle Scholar
  18. 18.
    Kosower EM (1970) A role for glutathione in muscle contraction. Experienta 26:76–77Google Scholar
  19. 19.
    Kosower NS, Kosower EM (1978) The glutathione status of cells. Intern Rev Cytol 54:109–160Google Scholar
  20. 20.
    Myers ML, Bolli R, Lekich RF, Hartley CJ, Roberts R (1985) Enhancement of recovery of myocardial function by oxygen free-radical scavengers after reversible regional ischemia. Circulation 72:915–921PubMedGoogle Scholar
  21. 21.
    Morano I, Arndt H, Gärtner C, Rüegg JC (1987) Skinned fibers of human atrium and ventricle myosin isoenzymes and contractility. Circ Res 62:632–639Google Scholar
  22. 22.
    Nohl H, Jordan W (1980) The metabolic fate of mitochondrial hydrogen peroxide. Eur J Biochem 111:203–210PubMedGoogle Scholar
  23. 23.
    Pyke S, Lew H, Quintanilha A (1986) Severe depletion in liver glutathione during physical exercise. Biochem and Biophys Res Commun 139:926–931Google Scholar
  24. 24.
    Röth E, Török B, Pollák Z, Temes G, Morvay G (1987) Myocardial protection by antioxidant during permanent and temporary coronary occlusion in dogs. Basic Res Cardiol 82:335–345PubMedGoogle Scholar
  25. 25.
    Simpson PJ, Fantone JC, Lucchesi BR (1988) Myocardial ischemia and reperfusion injury: oxygen radicals and the role of the neutrophil. In: Halliwell B (ed) Oxygen radicals and tissue injury. Fed Am Soc Exper Biol, pp 63–80Google Scholar
  26. 26.
    Thayer WS (1988) Evaluation of tissue indicators of oxydative stress in rat hearts treated chronically with adriamycin. Biochem Pharmacol 37:2189–2194PubMedGoogle Scholar

Copyright information

© Dr. Dietrich Steinkopff Verlag 1989

Authors and Affiliations

  • S. F. Bauer
    • 1
  • K. Schwarz
    • 1
  • J. C. Rüegg
    • 1
  1. 1.II. Physiological InstituteUniversity of HeidelbergHeidelbergFRG

Personalised recommendations