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:

The agonist effect of dihydropyridines on Ca channels

Nature volume 311, pages 570–572 (1984)Cite this article

Abstract

Dihydropyridines (DHP) have great potential for clinical use because of their inotropic and vasomotor effects. The mechanism of action is unknown although Ca currents have been implicated1,2. Here we report measurements of single channel and whole cell cardiac Ca currents after application of two DHP agonists BAY K 8644 and CGP 28 392. Whole cell Ca currents from individual myocytes were increased and the 50% effective doses (ED50) were similar to those reported for contractility in rabbit aorta and guinea pig heart1 and catecholamine release from cat adrenal glands3. The measured ED50 was also consistent with the apparent dissociation constant (Kd) of a high affinity binding site present in cardiac sarcolemmal vesicles4–7. We propose that the molecular basis for these results is an increase in the probability that a single Ca channel, having opened and closed, will subsequently re-open during membrane depolarization. At high concentrations of BAY K 8644 and in the presence of 96 mM Ba, different effects are observed, primarily a marked prolongation of open time8.

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

Access options

Buy this article

  • Purchase on SpringerLink
  • 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. Schramm, M., Thomas, G., Towart, R. & Franckowiak, G. Nature 303, 535–537 (1983).

    Article  ADS  CAS  Google Scholar 

  2. Glossman, H., Ferry, D. R., Lübbecke, F., Mewes, R. & Hofmann, F. Trends pharmac. Sci. 3, 431–437 (1982).

    Article  Google Scholar 

  3. Garcia, A. G. et al. Nature 309, 69–71 (1984).

    Article  ADS  CAS  Google Scholar 

  4. Janis, R. A., Rampe, D., Sarmiento, J. G. & Triggle, D. J. Biochem. biophys. Res. Commun. (in the press).

  5. Sarmiento, J. G., Janis, R. A., Rampe, D. & Triggle, D. J. Fedn Proc. 43, 448 (1984).

    Google Scholar 

  6. Vaghy, P. L., Grupp, I. L., Grupp, G. & Schwartz, A. Circulation Res. (in the press).

  7. Grupp, I. L. et al. Fedn Proc. 43, 937 (1984).

    MathSciNet  Google Scholar 

  8. Hess, P., Lansman, J. B. & Tsien, R. W. Biophys. J. 45, 394a (1984).

    Google Scholar 

  9. Mark, G. E. & Strasser, F. F. Expl Cell Res. 44, 217–233 (1966).

    Article  CAS  Google Scholar 

  10. Powell, T., Terrar, D. A. & Twist, V. W. J. Physiol., Lond. 302, 131–153 (1980).

    Article  CAS  Google Scholar 

  11. Taniguchi, J., Kokubun, S., Noma, A. & Irisawa, H. Jap. J. Physiol. 31, 547–558 (1981).

    Article  CAS  Google Scholar 

  12. Isenberg, G. & Klockner, U. Pflügers Arch. ges. Physciol. 395, 6–18 (1982).

    Article  CAS  Google Scholar 

  13. Hamill, O. P., Marty, A., Neher, E., Sakmann, B. & Sigworth, F. J. Pflügers Arch. ges. Physiol. 391, 85–100 (1981).

    Article  CAS  Google Scholar 

  14. Johnson, E. A. & Lieberman, M. A. Rev. Physiol. 33, 479–532 (1971).

    Article  CAS  Google Scholar 

  15. Moses, R. L. & Kasten, F. H. Cell Tissue Res. 203, 173–180 (1979).

    Article  CAS  Google Scholar 

  16. Josephson, I., Sanchez-Chapula, J. & Brown, A. M. Circulation Res. 54, 157–162 (1984).

    Article  CAS  Google Scholar 

  17. Sanguinetti, M. C. & Kass, R. S. Biophys. J. 45, 394a (1984).

  18. Reuter, H., Stevens, C. F., Tsien, R. W. & Yellen, G. Nature 297, 501–504 (1983).

    Article  Google Scholar 

  19. Cachelin, A. B., de Peyer, J. E., Kokubun, S. & Reuter, H. Nature 304, 462–464 (1983).

    Article  ADS  CAS  Google Scholar 

  20. Fenwick, E. M., Marty, A. & Neher, E. J. Physiol., Lond. 331, 599–635 (1982).

    Article  CAS  Google Scholar 

  21. Hagiwara, S. and Ohmori, H. J. Physiol., Lond. 336, 649–661 (1983).

    Article  CAS  Google Scholar 

  22. Lux, H. D. & Nagy, K. Pflügers Arch. ges. Physiol. 391, 252–254 (1981).

    Article  CAS  Google Scholar 

  23. Brown, A. M., Camerer, H., Kunze, D. L. & Lux, H. D. Nature 299, 156–158 (1982).

    Article  ADS  CAS  Google Scholar 

  24. Cavalié, A., Ochi, R., Pelzer, D. & Trautwein, W. Pflügers Arch. ges. Physiol. 398, 284–297 (1983).

    Article  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Physiology and Biophysics, University of Texas Medical Branch, Galveston, Texas, 77550, USA

    A. M. Brown, D L. Kunze & A. Yatani

Authors
  1. A. M. Brown
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. D L. Kunze
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. A. Yatani
    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

Brown, A., Kunze, D. & Yatani, A. The agonist effect of dihydropyridines on Ca channels. Nature 311, 570–572 (1984). https://doi.org/10.1038/311570a0

Download citation

  • Received:

  • Accepted:

  • Issue Date:

  • DOI: https://doi.org/10.1038/311570a0

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