Glutathione alters calcium responsiveness of cardiac skinned fibers
- 30 Downloads
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 wordsglutathione skinnedcardiac fiber oxidative stress calcium regulation
Unable to display preview. Download preview PDF.
- 1.Balentine JD (1982) Pathology of oxygen toxicity. Academic Press, New York LondonGoogle Scholar
- 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
- 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
- 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.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
- 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
- 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
- 18.Kosower EM (1970) A role for glutathione in muscle contraction. Experienta 26:76–77Google Scholar
- 19.Kosower NS, Kosower EM (1978) The glutathione status of cells. Intern Rev Cytol 54:109–160Google Scholar
- 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
- 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
- 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