Investigation of the cellular mechanisms of actions of digoxin and monensin by using guinea-pig papillary muscles

Year 2009, Volume: 3 Issue: 3, 1 - 5, 01.11.2009

Ramazan Üstün , İsmail Meral

Abstract

This experiment was carried out to determine the possible mechanism of actions of monensin and digoxin by using guinea-pig papillary muscles. A total of 120 papillary muscles obtained from 60 guinea-pigs were used. Three treatment groups; control (%0,1 ethanol), monensin (10 μmol/l) and digoxin (3 μmol/l) were compared in normal, Na+-free, Ca2+-free, and thapsigargin-added Krebs solutions. It was found that both digoxin and monensin caused a positive inotropic effect in normal and Ca2+-free Krebs solutions. Although monensin produced a positive inotropic effect in thapsigargin-treated papillary muscles, digoxin did not show a positive inotropic effect. Because papillary muscles in Na+ -free Krebs solution showed spontaneous contractions, trusted results were not obtained in Na+ -free medium. It is concluded that monensin produces a positive inotropic effect by depending on both extracellular Ca2+ and Ca2+ released from the sarcoplasmic reticulum (SR). Digoxin, on the other hand, produces its effect by depending on the Ca2+ released from SR.

Keywords

Monensin, digoxin, guinea pig, papillary muscle

References

• Balzan, S., G. D’Urso, S. Ghione, A. Martinelli, and U. Montali, 2000: Selective inhibition of human erythrocyte Na+/K+ ATPase by cardiac glycosides and by a mammalian digitalis like factor. Life Sci. 67, 1921–1928.
• Barry, W. H., and J. H. B. Bridge, 1993: Intracellularr calcium homeostasis in cardiac myocytes. Circulation 87, 1806–1815.
• Deitmer, J. W., and D. Ellis, 1978: Intracellular sodium activity of cardiac purkinje fibers during inhibition and reactivation of the Na-K pump. J. Physiol. (Lond.) 284, 241–259.
• Ehara, T., A. Noma, and K. Ono, 1988: Calcium-activated non-selective cation channel in ventricular cells isolated from adult guinea-pig hearts. J. Physiol. (Lond.) 403, 117–133.
• Fabiato, A., 1985: Simulated calcium current can both cause calcium loading in and trigger calcium release from sarcoplasmic reticulum of a skinned canine cardiac purkinje cell. J. Gen. Physiol. 85, 291–320.
• Hugtenburg, J. G., M. J. Mathy, J. J. Beckeringh, and P. A. Van Zwiten, 1989: The differential effect of calcium antagonists on the positive inotropic effects induced by calcium and monensin in cardiac preparations of rats and guinea-pigs. Naunyn-Schmiedeberg’s Arch. Pharmacol. 340, 558–566.
• Meral, I., 1998: Effects of different concentrations of Monensin on the contractility changes of guinea-pig papillary muscles. Tr. J. Vet. Ani. Sci. 22, 145–149.
• Meral, I., Hembrough, F. B., Bailey, T. B., and W. Hsu, 2002a: Functional changes in isolated guinea-pig papillary muscle induced by monensin and digoxin. J. Vet. Med. A Physiol. Pathol. Clin. Med. 49(1), 51-56.
• Meral, I., Hsu, W., and F. B., Hembrough, 2002b: Digoxin- and monensin-induced changes of intracellular Ca2+ concentration in isolated guinea-pig ventricular myocyte. J. Vet. Med. A Physiol. Pathol. Clin. Med. 49(6), 329-333.
• Miura, D. S., and S. Biedert, 1985: Cellular mechanisms of digitalis action. J. Clin. Pharmacol. 25, 490–500.
• Mollenhauer, H. H., D. J. Morre, and L. D. Rowe, 1990: Alteration of intracellular traffic by monensin; mechanism, specificity and relationship to toxicity. Biochim. Biophys. Acta 1031, 225–246.
• Muller-Ehmsen, J., K. Frank, K. Brixius, and R. H. Schwinger, 1997: Increase in force of contraction by activation of the Na+/Ca (2+)-exchanger in human myocardium. Br. J. Clin. Pharmacol. 43, 399–405.
• Nagai, K., T. Murakami, T. Iwase, T. Tomita, and S. Sasayama, 1996: Digoxin reduces beta-adrenergic contractile response in rabbit hearts. Ca (2+)-dependent inhibition of adenylyl cyclase activity via Na+/Ca2+ exchange. J. Clin. Invest. 97, 6–13.
• Satoh, H., and K. Tsuchida, 1999: Pharmacological actions of monovalent ionophores on spontaneously beating rabbit sino-atrial nodal cells. Gen. Pharmacol. 33, 151–159.
• Snedecor, G. W., and W. G. Cochran, 1989: Statistical Methods, 8th edn, pp. 227. Iowa State University Press, Ames, IA, USA.
• Somberg, J., and B. Greenfield, 1985: Digitalis: Historical development in clinical medicine. J. Clin. Pharmacol. 25, 484–489.
• Tsuchida, K., and S. Otomo, 1990: Electrophysiological effects of monensin, a sodium ionophore, on cardiac purkinje fibers. Eur. J. Pharmacol. 190, 313–320.