Hormonal and Non-Hormonal Regulation of Ca2+ Current and Adenylate Cyclase in Cardiac Cells
The influx of Ca2+ ions through transmembrane Ca2+ channels is fundamental in many aspects of cardiac function. Regulation of the heart beat by noradrenaline and acetylcholine (ACh) is in part mediated by the effects of these neurotransmitters on calcium current, ICa (1). β-adrenergic stimulation of ICa is mediated by a guanine-nucleotide binding protein, Gs (2), which triggers the activation of adenylate cyclase (AC) and in turn stimulates cAMP-dependent phosphorylation of Ca2+ channels (1,3). Gs has also been shown to directly activate Ca2+ channels (4). This latter mechanism, however, may play only a minor role in the physiological response to noradrenaline since the effects of β-adrenergic agonists on ICa were mimicked by external application of cAMP, its analogues or phosphodiesterase inhibitors (5), forskolin (6) [a direct activator of AC (7)], and by intracellular application of cAMP (8,9) or the catalytic subunit of cAMP-dependent protein kinase (PKA; ref. 8).
KeywordsAdenylate Cyclase Calcium Current External Solution Maximal Stimulation Ventricular Cell
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- 5.Tsien, R. W. Cyclic AMP and contractile activity in heart. Adv. Cycl. Nucl. Res. 8: 363–420, 1977.Google Scholar
- 7.Seamon, K. B. and Daly, J. W. Forskolin: its biological and chemical properties. Adv. Cycl. Nucl. Prot. Phosphor. Res. 20: 1–150, 1986.Google Scholar
- 16.Chatelain, P., Robberecht, P., Waelbroeck, M., De Neef, P., Camus, J.-C., Nguyen Hu, A., Roba, J. and Christophe, J. Topographical distribution of the secretin-and VIP-stimulated adenylate cyclase system in the heart of five animal species. Pflügers Arch. 397: 100–105, 1983.PubMedCrossRefGoogle Scholar
- 18.Méry, P.-F., Pavoine, C., Brechler, V., Pecker, F. and Fischmeister, R. (Submitted for publication).Google Scholar
- 19.Pucéat, M., Lechêne, P., Clément, O., Pelosin, J.-M., Ventura-Clapier, R. and Vassort, G. (Submitted for publication).Google Scholar
- 20.Buxton, I. L. O. and Brunton, L. L. Action of the cardiac α1-adrenergic receptor. Activation of cyclic AMP degradation. J. Biol. Chem. 26: 6733–6737, 1985.Google Scholar
- 21.Pecker, F., Duvaldestin, P., Berthelot, P. and Hanoune, J. The adenylate cyclase system in human liver: characterization, subcellular distribution and hormonal sensitivity in normal or cirrhotic adult, and in foetal liver. J. Clin. Sci. 57: 313–325, 1979.Google Scholar
- 23.Pollock, H. G., Hamilton, J. W., Rouse, J. B., Ebner, K. E. and Rawitch, A. B. Isolation of peptide hormones from the pancreas of the bullfrog (Rana catesbeiana). Amino acid sequences of pancreatic polypeptide, oxyntomodulin, and two glucagon-like peptides. J. Biol. Chem. 263: 9746–9751, 1988.PubMedGoogle Scholar
- 28.Wildenthal, K., Allen, D. O., Karlsson, J., Wakeland, J. R. and Clark, C. M. Responsiveness to glucagon in fetal hearts. Species variability and apparent disparities between changes in beating, adenylate cyclase activation, and cyclic AMP concentration. J. Clin. Inv. 57: 551–558, 1976CrossRefGoogle Scholar
- 35.Rodger, I. W. and Shahid, M. Forskolin, cyclic nucleotides and positive inotropism in isolated papillary muscles of the rabbit. Brit. J. Pharmacol. 81: 151–159, 1984.Google Scholar