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Inhibition of the cardiac protein kinase A-dependent chloride conductance by endothelin-1

Nature volume 370, pages 297–300 (1994)Cite this article

Abstract

ENDOTHELIN-1 is a peptide hormone constitutively secreted by vascular and endocardial endothelial cells1–3. Secretion of endothelin-1 is increased under certain pathophysiological conditions, including coronary vasospasm, cardiac ischaemia and myocardial infarction. We have examined the effect of endothelin-1 on the protein kinase A (PKA)-dependent chloride current in voltage-clamped guinea pig ventricular myocytes. This conductance, induced by catecholamines through β-adrenergic receptors, counteracts the simultaneously increased L-type calcium current by shortening the action potential duration4–6. We report here that endothelin-1, acting through ETA (endothelin-1-selective) receptors, inhibited the current through a pertussis toxin-sensitive mechanism, analogous to muscarinic receptors, by reducing the intracellular cyclic AMP concentration. This effect of endothelin-1 should help protect the ventricle against potentially arrhythmogenic shortening of the action potential during ischaemia when the circulating levels of catecholamines are increased.

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Authors and Affiliations

  1. International Research Laboratories, Ciba-Geigy Japan Ltd, Takarazuka, 665, Japan

    Andrew F. James & Yasushi Fujitani

  2. Department of Cellular and Molecular Physiology, National Institute for Physiological Sciences, Okazaki, 444, Japan

    Andrew F. James, Lai-Hua Xie & Seiji Hayashi

  3. 3rd Department of Internal Medicine, Faculty of Medicine, Kyoto University, Kyoto, 606, Japan

    Minoru Horie

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James, A., Xie, LH., Fujitani, Y. et al. Inhibition of the cardiac protein kinase A-dependent chloride conductance by endothelin-1. Nature 370, 297–300 (1994). https://doi.org/10.1038/370297a0

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