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The dual effects of ouabain on45Ca2+ transport and contractility in adult rat ventricular myocytes

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Abstract

We used isolated ventricular myocytes to study45Ca2+ transport in the presence of three concentrations of ouabain (10 nM, 1 μM, and 100 μM) in Tyrode solution containing 1 mM CaCl2. The cells were quiescent and during45Ca2+ uptake and45Ca2+ efflux experiments 10 nM ouabain decreased Ca2+ content, 1 μM, didn't change it appreciably, and 100 μM increased it significantly. Qualitatively, the same results were obtained at 22°C and 35°C. Ouabain did not significantly affect the electrical activity of isolated, electrically stimulated myocytes, but it increased the amplitude of shortenings of these myocytes in a dose-dependent manner. Thus, the positive inotropic effect of ouabain at therapeutic doses (≤10 nM) occurs in spite of decreased Ca2+ content, while at high toxic doses the positive inotropic effect is accompanied by an increment in Ca2+ content. These data support the hypothesis that the mechanisms of positive inotropy of ouabain are different at therapeutic and toxic concentrations of this drug. Finally, our study demonstrates that the effects of low doses of ouabain are independent of the release of endogenous catecholamines.

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References

  1. Adams RJ, Schwartz A, Grupp G, Grupp I, Lee S-W, Wallick ET, Powell T, Twist VW, Gathiram P (1982) High-affinity ouabain binding site and low-dose positive inotropic effect in rat myocardium. Nature 296:167–169

  2. Barry WH, Smith TW (1982) Mechanisms of transmembrane calcium movement in cultured chick embryonic ventricular cells. J Physiol (Lond) 325:243–260

  3. Bers DM, Allen L-AH, Kim Y (1986) Calcium binding to cardiac sarcolemmal vesicles: potential role as a modifier of contraction. Am J Physiol 251:C871-C871

  4. Bihler I, Ho, TK, Sawh PC (1984) Isolation of Ca2+-tolerant myocytes from adult rat heart. Can J Physiol Pharmacol 62:581–588

  5. Burt JM, Langer GA (1982) Ca distribution after Na+ pump inhibition in cultured neonatal rat myocardial cells. Circ Res 51:543–550

  6. Carrier GO, Lullmann H, Neubauer L, Peters T (1974) The significance of a rast exchanging superficial calcium fraction for the regulation of contractile force in heart muscle. J Mol Cell Cardiol 6:333–347

  7. Desilets M (1983)45Ca2+ transport and its Na-dependence in myocytes isolated from adult rat hearts. Dissertation Dalhousie University, Halifax, NS

  8. Desilets, M, Horackova M (1982) Na+-dependence of45Ca2+ uptake in adult rat isolated cardiac cells. Biochim Biophys acta 721:144–157

  9. Deslauriers Y, Ruiz-Ceretti E., Schanne OF, Payet MD (1982) The toxic effects of ouabain: voltage-clamp study. Can J Physiol Pharmacol 60:1153–1159

  10. Erdmann E, Philipp G, Scholz H (1980) Cardiac glycoside receptor, (Na+−K+) ATPase activity and force of contraction in rat heart. Biochem Pharmacol 29:3219–3229

  11. Erdmann E, Brown L, Werdan K (1984) Two receptors for cardiac glycosides in the heart. Basic Res Cardiol 79 (suppl):21–26

  12. Fischmeister R, Brocas-Randolph M, Lechene P, Jargibay A, Vassort G (1986) A dual effect of cardiac glycosides on Ca current in single cells of frog heart. Pflügers Arch 406:340–342

  13. Fozzard HA, Sheets MF (1985) Cellular mechanism of action of cardiac glycosides. J Am Coll Cardiol 5:10A-15A

  14. Godfraind T (1984) Mechanism of action of cardiac glycosides. Eur Heart J 5 (Suppl F):303–308

  15. Godfraind T, Ghysel-Burton J (1977) Binding sites related to ouabain-induced stimulation or inhibition of the sodium pump. Nature 265:165–166

  16. Grupp I, Im WB, Lee CHO, Lee SW, Pecker MS, Schwartz A (1985) Relation of sodium pump inhibition to positive inotropy at low concentrations of ouabain in rat heart muscle. J Physiol (Lond) 360:149–160

  17. Hart G, Noble D, Shimoni Y (1983) The effects of low concentrations of cardiotonic steroids on membrane currents and tension in sheep Purkinje fibres. J Physiol (Lond) 334:103–131

  18. Horackova M (1986) Excitation-contraction, coupling in isolated adult ventricular myocytes from the rat, dog and rabbit: effects of various inotropic interventions in the presence of ryanodine. Can J Physiol Pharmacol 64:1473–1483

  19. Horackova M, Vassort G (1979) Sodium-calcium exchange in regulation of cardiac contractility. J Gen Physiol 73:403–424

  20. Hougen TJ, Spicer N, Smith TW (1981) Stimulation of monovalent cation active transport by low concentrations of cardiac glycosides: role of catecholamines. J Clin Invest 68:1209–1214

  21. Isenberg G (1984) Contactility of isolated bovine ventricular myocytes is enhanced by intracellular injection of cardioactive glycosides: Evidence for an intracellular mode of action. Basic Res Cardiol 79 (suppl):56–71

  22. Josephson I, Sperelakis N (1977) Ouabain blockade of inward slow current in cardiac muscle. J Mol Cell Cardiol 9:409–418

  23. Koch-Weser J, Blinks JR (1962) Analysis of the relation of the positive inotropic action of cardiac glycosides to the frequency of contraction of heart muscle. J Pharmacol 136:305–317

  24. Langer GA (1977) Relationship between myocardial contractility and the effects of digitalis on ionic exchange. Fed Proc Fed Am Soc Exp Biol 36:2231–2234

  25. Lechat P, Malloy CR, Smith TW (1983) Active transport and inotropic state in guinea-pig left atrium. Circ Res 52:411–422

  26. Lederer WJ, Eisner DA (1982) The effects of sodium pump activity on the slow inward current in sheep cardiac Purkinje fibres. Proc R Soc. London B 214:249–262

  27. Lee CO (1985) 200 Years of digitalis: the emerging central role of the sodium ion in the control of cardiac force Am J Physiol 249:C367-C378

  28. Levinson C, Blumenson LE (1970) Calcium transport and distribution in Ehrlich mouse ascites tumor cells. J Cell Physiol 75:231–240

  29. Marban E, Tsien RW (1982) Enhancement of calcium current during digitalis inotropy in mammalian heart: positive feed-back regulation by intracellular calcium? J Physiol (Lond) 329:589–614

  30. Mentrard D, Vassort G, Fischmeister R (1984) Calcium-mediated inactivation of the calcium conductance in cesium-loaded frog heart cells. J Gen. Physiol 83:105–131

  31. Nayler WG (1973) An effect of ouabain on the superficially-located stores of calcium in cardiac muscle cells. J Mol Cell Cardiol 5:101–110

  32. Noble D (1980) Mechanism of action of therapeutic levels of cardiac glycosides. Cardiovasc Res 14:495–514

  33. Palmer RF, Lasseter KC, Melvin SL (1966) Stimulation of Na+ and K+ dependent adenosine triphosphatase by ouabain. Arch Biochem Biophys 113:629–633

  34. Weingart R, Kass RS, Tsien RW (1978) Is digitalis inotropy associated with enhanced slow inward calcium current? Nature 273:389–392

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Correspondence to M. Horackova.

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Horackova, M., Mullen, S. The dual effects of ouabain on45Ca2+ transport and contractility in adult rat ventricular myocytes. Pflugers Arch. 412, 277–284 (1988). https://doi.org/10.1007/BF00582509

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Key words

  • Isolated cardiac myocytes
  • Excitation-contraction coupling
  • Cardiac glycosides
  • Positive inotropic effect
  • Na+−K+ pump
  • Na+−Ca2+ exchange