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Endothelin-A receptor mediates cardiac inhibition by regulating calcium and potassium currents

Nature volume 370, pages 301–304 (1994)Cite this article

Abstract

VOLTAGE-SENSITIVE ion channels play fundamental roles in the regulation of cardiac function by various neurotransmitters1,2. Endothelins3 have strong positive inotropic4 and chronotropic5 effects, for which recent studies have implicated various intracellular mechanisms6,7. However, very little is known about the underlying ion-channel regulation by the peptide. We report here that endothelin-1 consistently hyperpolarizes the membrane and shortens the duration of the action potential in mammalian atrial myocytes, leading to suppression of electrical excitability of the heart. Endothelin-1, but not endothelin-3, inhibited the L-type calcium current by decreasing cyclic AMP accumulation and activated the muscarinic potassium current by stimulating a pertussis toxin-sensitive GTP-binding protein. Consistent with these results, endothelin-1 strongly reduced the heart rate when it was increased by β-adrenoceptor stimulation. These effects were blocked by an ETA (endothelin-1-selective) receptor-selective antagonist, BQ123 (refs 8–11). The ETA receptor-mediated regulation of cardiac ion channels gives new insight into our understanding of the physiological and pathophysiological roles of endothelins in the control of cardiac function.

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References

  1. Ono, K., Delay, M., Nakajima, T., Irisawa, H. & Giles, W. Nature 340, 721–724 (1989).

    Article  ADS  CAS  Google Scholar 

  2. Reuter, H. A. Rev. Physiol. 41, 413–424 (1979).

    Article  CAS  Google Scholar 

  3. Yanagisawa, M. et al. Nature 332, 411–415 (1988).

    Article  ADS  CAS  Google Scholar 

  4. Ishikawa, T., Yanagisawa, M., Kimura, S., Goto, K. & Masaki, T. Am. J. Physiol. 255, H970–H973 (1988).

    CAS  PubMed  Google Scholar 

  5. Ishikawa, T., Yanagisawa, M., Kimura, S., Goto, K. & Masaki, T. Pflügers Arch. ges. Physiol. 413, 108–110 (1988).

    Article  CAS  Google Scholar 

  6. Masaki, T., Yanagisawa, M. & Goto, K. Med. Res. Rev. 12, 391–421 (1992).

    Article  CAS  Google Scholar 

  7. Aramori, I. & Nakanishi, S. J. biol. Chem. 267, 12468–12474 (1992).

    CAS  PubMed  Google Scholar 

  8. Ihara, M. et al. Life Sci. 50, 247–255 (1992).

    Article  CAS  Google Scholar 

  9. Arai, H., Hori, S., Aramori, I., Ohkubo, H. & Nakanishi, S. Nature 348, 730–732 (1990).

    Article  ADS  CAS  Google Scholar 

  10. Sakamoto, A. et al. J. biol. Chem. 268, 8547–8553 (1993).

    CAS  PubMed  Google Scholar 

  11. Sakurai, T. et al. Nature 348, 732–735 (1990).

    Article  ADS  CAS  Google Scholar 

  12. Franco-Cereceda, A., Matran, R., Lou, Y.-P. & Lundberg, J. M. Acta physiol. scand. 138, 539–547 (1990).

    Article  CAS  Google Scholar 

  13. Tohse, N., Hattori, Y., Nakaya, H., Endou, M. & Kanno, M. Br. J. Pharmac. 99, 437–438 (1990).

    Article  CAS  Google Scholar 

  14. Hartzell, H. C. & Simmons, M. A. J. Physiol., Lond. 389, 411–422 (1987).

    Article  CAS  Google Scholar 

  15. Pfaffinger, P. J., Martin, J. M., Hunter, D. D., Nathanson, N. M. & Hille, B. Nature 317, 536–538 (1985).

    Article  ADS  CAS  Google Scholar 

  16. Kim, D. Circ. Res. 69, 250–255 (1991).

    Article  CAS  Google Scholar 

  17. Sakamoto, A. et al. Biochem. biophys. Res. Commun. 178, 656–663 (1991).

    Article  CAS  Google Scholar 

  18. Inoue, A. et al. Proc. natn. Acad. Sci. U.S.A. 86, 2863–2867 (1989).

    Article  ADS  CAS  Google Scholar 

  19. Tanaka, T. et al. Molec. Pharmac. 45, 724–730 (1994).

    CAS  Google Scholar 

  20. Ishikawa, T. et al. Circ. Res. 69, 918–926 (1991).

    Article  CAS  Google Scholar 

  21. Hori, S., Komatsu, Y., Shigemoto, R., Mizuno, N. & Nakanishi, S. Endocrinology 130, 1885–1895 (1992).

    CAS  PubMed  Google Scholar 

  22. Hilal-Dandan, R., Urasawa, K. & Brunton, L. L. J. biol. Chem. 267, 10620–10624 (1992).

    CAS  PubMed  Google Scholar 

  23. Vogelsang, M., Broede-Sitz, A., Schäfer, E., Zerkowski, H.-R. & Brodde, O.-E. J. cardiovasc. Pharmac. 23, 344–347 (1994).

    Article  CAS  Google Scholar 

  24. Wennmalm, A., Benthin, G., Karwatowska-Prokopczuk, E., Lundberg, J. & Petersson, A.-S. J. Physiol., Lond. 435, 163–173 (1991).

    Article  CAS  Google Scholar 

  25. Reid, J. J., Lieu, A. T. & Rand, M. J. Eur. J. Pharmac. 194, 173–181 (1991).

    Article  CAS  Google Scholar 

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

    Article  CAS  Google Scholar 

  27. Ono, K. & Giles, W. R. J. Physiol., Lond. 436, 195–217 (1991).

    Article  CAS  Google Scholar 

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Author notes

  1. Gozoh Tsujimoto, Aiji Sakamoto and Koji Eto: Division of Molecular and Cellular Pharmacology, National Children's Medical Research Centre, 3-35-31 Taishido, Setagaya-ku, Tokyo 154, Japan

  2. Tomoh Masaki: Department of Pharmacology, Faculty of Medicine, Kyoto University, Yoshida-Konoe-cho, Sakyo-ku, Kyoto 606-01, Japan

Authors and Affiliations

  1. Division of Chemical Pharmacology and Phytochemistry, National Institute of Health Sciences, 1-18-1 Kami-Yohga, Setagaya-ku, Tokyo, 158, Japan

    Kageyoshi Ono, Gozoh Tsujimoto, Aiji Sakamoto, Koji Eto, Tomoh Masaki, Yukihiro Ozaki & Motoyoshi Satake

Authors
  1. Kageyoshi Ono
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Ono, K., Tsujimoto, G., Sakamoto, A. et al. Endothelin-A receptor mediates cardiac inhibition by regulating calcium and potassium currents. Nature 370, 301–304 (1994). https://doi.org/10.1038/370301a0

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