Skip to main content
PMC home page
Proceedings of the National Academy of Sciences of the United States of America logoLink to Proceedings of the National Academy of Sciences of the United States of America
. 1980 May;77(5):3067–3069. doi: 10.1073/pnas.77.5.3067

Independence of the positive inotropic effect of ouabain from the inhibition of the heart Na+/K+ pump.

T Godfraind, J Ghysel-Burton
PMCID: PMC349548  PMID: 6248887

Abstract

Isolated left atria from guinea pigs were stimulated at 3.3 Hz and bathed at 30 degrees C in Tyrode's solution containing 6 mM KCl. After equilibration, this solution was replaced by a low-K solution or by Tyrode's solution containing ouabain or dihydroouabain. These treatments evoked an increase in the contractility of the atria. The time to peak increase was about 30 min, and the inotropic effect was sustained for at least 40 min. After 30 min, 42K was added to the bathing solution in order to estimate the activity of the Na+/K+ pump. A linear relationship was observed between the degree of inhibition of the Na+/K+ pump and the increase in systolic tension. The regression line was the same for low-K solutions and dihydroouabain but not for ouabain. For a given degree of inhibition of the pump, ouabain evoked a higher increase in contractility. These findings indicate that inhibition of the Na+/K+ pump can be the only mechanism responsible for the positive inotropic effect of dihydroouabain but cannot be the sole mechanism for that of ouabain.

Full text

PDF
3067

Images in this article

3068Image
on p.3068

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Akera D. K., Brody T. M., Ku D., Pew C. L. Cardiac glucosides: correlations among Na+ K+-ATPase, sodium pump and contractility in the guinea pig heart. Naunyn Schmiedebergs Arch Pharmacol. 1974;285(2):185–200. doi: 10.1007/BF00501153. [DOI] [PubMed] [Google Scholar]
  2. Akera T., Larsen F. S., Brody T. M. Correlation of cardiac sodium- and potassium-activated adenosine triphosphatase activity with ouabain-induced inotropic stimulation. J Pharmacol Exp Ther. 1970 May;173(1):145–151. [PubMed] [Google Scholar]
  3. Besch H. R., Jr, Watanabe A. M. The positive inotropic effect of digitoxin: independence from sodium accumulation. J Pharmacol Exp Ther. 1978 Dec;207(3):958–965. [PubMed] [Google Scholar]
  4. Brody T. M., Akera T. Relations among Na+,K+-ATPase activity, sodium pump activity, transmembrane sodium movement, and cardiac contractility. Fed Proc. 1977 Aug;36(9):2219–2224. [PubMed] [Google Scholar]
  5. Cohen I., Daut J., Noble D. The effects of potassium and temperature on the pace-maker current, iK2, in Purkinje fibres. J Physiol. 1976 Aug;260(1):55–74. doi: 10.1113/jphysiol.1976.sp011504. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Deitmer J. W., Ellis D. The intracellular sodium activity of cardiac Purkinje fibres during inhibition and re-activation of the Na-K pump. J Physiol. 1978 Nov;284:241–259. doi: 10.1113/jphysiol.1978.sp012539. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Eisner D. A., Lederer W. J. The role of the sodium pump in the effects of potassium-depleted solutions on mammalian cardiac muscle. J Physiol. 1979 Sep;294:279–301. doi: 10.1113/jphysiol.1979.sp012930. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Ghysel-Burton J., Godfraind T. Importance of the lactone ring for the action of therapeutic doses of ouabain in guinea-pig atria [proceedings]. J Physiol. 1977 Mar;266(1):75P–76P. [PubMed] [Google Scholar]
  9. Ghysel-Burton J., Godfraind T. Stimulation and inhibition of the sodium pump by cardioactive steroids in relation to their binding sites and their inotropic effect on guinea-pig isolated atria. Br J Pharmacol. 1979 Jun;66(2):175–184. doi: 10.1111/j.1476-5381.1979.tb13662.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Glitsch H. G., Reuter H., Scholz H. The effect of the internal sodium concentration on calcium fluxes in isolated guinea-pig auricles. J Physiol. 1970 Jul;209(1):25–43. doi: 10.1113/jphysiol.1970.sp009153. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Godfraind T. Calcium exchange in vascular smooth muscle, action of noradrenaline and lanthanum. J Physiol. 1976 Aug;260(1):21–35. doi: 10.1113/jphysiol.1976.sp011501. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Godfraind T., Ghysel-Burton J. Binding sites related to ouabain-induced stimulation or inhibition of the sodium pump. Nature. 1977 Jan 13;265(5590):165–166. doi: 10.1038/265165a0. [DOI] [PubMed] [Google Scholar]
  13. Godfraind T., Lesne M. The uptake of cardiac glycosides in relation to their actions in isolated cardiac muscle. Br J Pharmacol. 1972 Nov;46(3):488–497. doi: 10.1111/j.1476-5381.1972.tb08146.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Hougen T. J., Lloyd B. L., Smith T. W. Effects of inotropic and arrhythmogenic digoxin doses and of digoxin-specific antibody on myocardial monovalent cation transport in the dog. Circ Res. 1979 Jan;44(1):23–31. doi: 10.1161/01.res.44.1.23. [DOI] [PubMed] [Google Scholar]
  15. Langer G. A. Ion fluxes in cardiac excitation and contraction and their relation to myocardial contractility. Physiol Rev. 1968 Oct;48(4):708–757. doi: 10.1152/physrev.1968.48.4.708. [DOI] [PubMed] [Google Scholar]
  16. REPKE K., PORTIUS H. J. UBER DIE IDENTITAET DER IONENPUMPEN-ATPASE IN DER ZELLMEMBRAN DES HERZMUSKELS MIT EINEM DIGITALIS-REZEPTORENZYM. Experientia. 1963 Sep 15;19:452–458. doi: 10.1007/BF02150643. [DOI] [PubMed] [Google Scholar]
  17. Thomas R., Boutagy J., Gelbart A. Cardenolide analogs. V. Cardiotonic activity of semisynthetic analogs of digitoxigenin. J Pharmacol Exp Ther. 1974 Nov;191(2):219–231. [PubMed] [Google Scholar]
  18. Weingart R., Kass R. S., Tsien R. W. Is digitalis inotropy associated with enhanced slow inward calcium current? Nature. 1978 Jun 1;273(5661):389–392. doi: 10.1038/273389a0. [DOI] [PubMed] [Google Scholar]
  19. den Hertog A., Ritchie J. M. A comparison of the effect of temperature, metabolic inhibitors and of ouabain on the electrogenic componen of the sodium pump in mammalian non-myelinated nerve fibres. J Physiol. 1969 Oct;204(3):523–538. doi: 10.1113/jphysiol.1969.sp008929. [DOI] [PMC free article] [PubMed] [Google Scholar]

Articles from Proceedings of the National Academy of Sciences of the United States of America are provided here courtesy of National Academy of Sciences

RESOURCES