Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • Letter
  • Published:

Is digitalis inotropy associated with enhanced slow inward calcium current?

Nature volume 273, pages 389–392 (1978)Cite this article

Abstract

THE positive inotropic effect of digitalis compounds is generally attributed to an increase in the amount of activator calcium1 and not to a change in the calcium sensitivity of regulatory contractile proteins2,3. The main question is the cellular or subcellular basis of the increase in the myoplasmic calcium transient. Since calcium entry through the slow inward current may play an important part in excitation–contraction coupling, it has been suggested that the slow inward current might be enhanced by digitalis4,5. All the evidence has been negative6–11 apart from a report by Dramane et al.12 and results of H. Brown, W. Giles and S. Noble (personal communication). We have re-examined this question and have found that strophanthidin can increase the slow inward current and alter its re-priming kinetics in certain conditions. These observations may provide a partial explanation of the positive inotropic effect observed in the same experiments.

This is a preview of subscription content, access via your institution

Access options

Buy this article

  • Purchase on Springer Link
  • Instant access to full article PDF
Buy now

Prices may be subject to local taxes which are calculated during checkout

Similar content being viewed by others

References

  1. Lee, K. S. & Klaus, W. Pharmac. Rev. 23, 193–261 (1971).

    CAS  Google Scholar 

  2. Fabiato, A. & Fabiato, F. Eur. J. Cardiol. 1, 143–155 (1973).

    CAS  PubMed  Google Scholar 

  3. Nayler, W. Am. J. Physiol. 225, 918–924 (1973).

    CAS  PubMed  Google Scholar 

  4. Katz, A. M. J. molec. cell. Cardiol. 4, 87–89 (1972).

    Article  CAS  Google Scholar 

  5. Fozzard, H. A. Circulation 47, 5–7 (1973).

    Article  CAS  PubMed  Google Scholar 

  6. Scholz, H. Naunyn-Schmiedeberg's Arch. Pharmac. 266, 445 (1970); in Recent Advances in Studies on Cardiac Structure and Metabolism 5, (eds Fleckenstein, A. & Dhalla, N. S.) 35–41 (University Park Press, Baltimore, 1975).

    Google Scholar 

  7. Tritthart, H., Weiss, R., Volkmann, R. & Späh, F. Naunyn-Schmiedebergs Arch. Pharmac. 282, R99 (1974).

    Google Scholar 

  8. Thyrum, P. T. J. Pharmac. exp. Ther. 188, 166–179 (1974).

    CAS  Google Scholar 

  9. Greenspan, A. M. & Morad, M. J. Physiol., Lond. 253, 357–384 (1975).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  10. McDonald, T. F., Nawrath, H. & Trautwein, W. Circulation Res. 37, 674–682 (1976).

    Article  Google Scholar 

  11. Josephson, I. & Sperelakis, N. J. molec. Cell. Cardiol. 9, 409–418 (1977).

    Article  CAS  Google Scholar 

  12. Dramane, K., Driot, P. & Garnier, D. J. Physiol., Paris 63, 43A (1971).

    CAS  Google Scholar 

  13. Blood, B. E. J. Physiol., Lond. 251, 69–70P (1975).

    Google Scholar 

  14. Cohen, I., Daut, J. & Noble, D. J. Physiol., Lond. 260, 75–103 (1976).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  15. Ellis, D. J. Physiol., Lond. 273, 211–240 (1977).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  16. Deck, K. A., Kern, R. & Trautwein, W. Pflugers Arch. 280, 50–62 (1964).

    Article  CAS  Google Scholar 

  17. Weidmann, S. J. Physiol., Lond. 127, 213–224 (1955).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  18. Gibbons, W. R. & Fozzard, H. A. J. gen. Physiol. 65, 367–384 (1975).

    Article  CAS  PubMed  Google Scholar 

  19. Siegelbaum, S. A., Tsien, R. W. & Kass, R. S. Nature 269, 611–613 (1977).

    Article  ADS  CAS  PubMed  Google Scholar 

  20. Reiter, M. Naunyn-Schmiedebergs Arch. Pharmac. 242, 497–507 (1962).

    Article  CAS  Google Scholar 

  21. Ferrier, G. R. Circulation Res. 38, 156–162 (1976); 41, 622–629 (1977).

    Article  CAS  PubMed  Google Scholar 

  22. Isenberg, G. & Trautwein, W. pflugers Arch. 350, 41–54 (1974).

    Article  CAS  PubMed  Google Scholar 

  23. Reuter, H. J. Physiol., Lond. 192, 479–492 (1967).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  24. Vassort, G. et al. Pflugers Arch. 309, 70–81 (1969).

    Article  CAS  PubMed  Google Scholar 

  25. Tsien, R. W. Adv. Cyclic Nucleotide Res. 8, 363–420 (1977).

    CAS  PubMed  Google Scholar 

  26. Gibbons, W. R. & Fozzard, H. A. Circulation Res. 28, 446–460 (1971).

    Article  CAS  PubMed  Google Scholar 

  27. Lederer, W. J. & Tsien, R. W. J. Physiol., Lond. 263, 73–100 (1976).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  28. Reuter, H. Prog. Biophys. molec. Biol. 26, 1–43 (1973).

    Article  CAS  Google Scholar 

  29. Kass, R. S., Tsien, R. W. & Weingart, R. J. Physiol., Lond. (in the press).

  30. Hiraoka, M. & Sano, T. in Recent Advances in Studies on Cardiac Structure and Metabolism (ed. Dhalla, N. S.) (in the press).

  31. Ferrier, G. R. Prog. Cardiovascular Dis. 19, 459–474 (1977).

    Article  CAS  Google Scholar 

  32. Kass, R. S., Siegelbaum, S. A. & Tsien, R. W. J. Physiol., Lond. 263, 127–128P (1976).

    Google Scholar 

  33. Langer, G. A. & Serena, S. D. J. molec. cell. Cardiol. 1, 65–90 (1970).

    Article  CAS  Google Scholar 

  34. Bailey, L. & Sures, H. A. J. Pharm. exp. Ther. 178, 259–270 (1971).

    CAS  Google Scholar 

  35. Besch, H. R. & Schwartz, A. J. molec. cell. Cardiol. 1, 195–199 (1970).

    Article  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Physiology, Yale University School of Medicine, New Haven, Connecticut, 06510

    R. WEINGART, R. S. KASS & R. W. TSIEN

Authors
  1. R. WEINGART
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. R. S. KASS
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. R. W. TSIEN
    View author publications

    You can also search for this author in PubMed Google Scholar

Rights and permissions

Reprints and permissions

About this article

Cite this article

WEINGART, R., KASS, R. & TSIEN, R. Is digitalis inotropy associated with enhanced slow inward calcium current?. Nature 273, 389–392 (1978). https://doi.org/10.1038/273389a0

Download citation

  • Received:

  • Accepted:

  • Issue Date:

  • DOI: https://doi.org/10.1038/273389a0

This article is cited by

Comments

By submitting a comment you agree to abide by our Terms and Community Guidelines. If you find something abusive or that does not comply with our terms or guidelines please flag it as inappropriate.

Search

Advanced search

Quick links

Nature Briefing

Sign up for the Nature Briefing newsletter — what matters in science, free to your inbox daily.

Get the most important science stories of the day, free in your inbox. Sign up for Nature Briefing