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Calcitonin gene-related peptide regulates calcium current in heart muscle

Nature volume 340, pages 721–724 (1989)Cite this article

Abstract

THE influx of Ca2+ due to the transmembrane calcium current, ICa, has a fundamental role in cardiac pacemaker activity, in the action potential plateau and in excitation-contraction coupling. Both sympathetic and parasympathetic neurotransmitters can modulate ICa (ref. 1). Recent studies indicate that in both the cardiovascular2-7 and the central nervous systems8,9, nerve varicosities exist that contain a novel non-adrenergic, non-cholinergic peptide—calcitonin gene-related peptide (CGRP)10. Although CGRP is known to exert strong positive inotropic3-5,7,11 and chronotropic3,11 effects, as well as to cause vasodilatation2,6,12,13, very little is known about the ionic mechanisms of these effects14,15. Here we report that CGRP dramatically increases ICa in single heart cells. Although this CGRP-induced increase in ICa resembles the effect of β-adrenergic agonists, our results demonstrate some significant differences between the effects of CGRP and these agonists: (1) the increase due to CGRP cannot be blocked by β-adrenergic antagonists; (2) the CGRP-induced effect is transient; and, (3) CGRP can inhibit isoproterenol-stimulated ICa. Our results provide the first electrophysiological evidence that CGRP can significantly modulate ICa in the heart, and suggest a new additional mechanism for the neurogenic control of cardiac function.

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Author notes

  1. Wayne Giles: To whom correspondence should be addressed.

Authors and Affiliations

  1. Departments of Medical Physiology and Medicine, University of Calgary School of Medicine, Calgary, Alberta, Canada, T2N 4NI

    Kageyoshi Ono, Michael Delay, Toshiaki Nakajima, Hiroshi Irisawa & Wayne Giles

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  1. Kageyoshi Ono
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  2. Michael Delay
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  3. Toshiaki Nakajima
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  4. Hiroshi Irisawa
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Ono, K., Delay, M., Nakajima, T. et al. Calcitonin gene-related peptide regulates calcium current in heart muscle. Nature 340, 721–724 (1989). https://doi.org/10.1038/340721a0

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