Glucagon stimulates the cardiac Ca2+ current by activation of adenylyl cyclase and inhibition of phosphodiesterase

• Published in: Nature (London) Vol. 345; no. 6271; pp. 158 - 161
• Main Authors: MERY, P.-F, BRECHLER, V, PAVOINE, C, PECKER, F, FISCHMEISTER, R
• Format: Journal Article
• Language: English
• Published: London Nature Publishing 10.05.1990; Nature Publishing Group
• Subjects: 3',5'-Cyclic-AMP Phosphodiesterases; 3',5'-Cyclic-AMP Phosphodiesterases - antagonists & inhibitors; Acetylcholine; Acetylcholine - pharmacology; Adenylyl Cyclases; Adenylyl Cyclases - metabolism; Amphibians; Animals; Biological and medical sciences; Calcium Channels; Calcium channels (L-type); Calcium Channels - physiology; Calcium currents; Calcium ions; Cardiac function; Cardiac muscle; Cardiology and cardiovascular system; Cyclic AMP; Cyclic AMP - biosynthesis; Cyclic AMP - pharmacology; Drug Synergism; Electric Conductivity; Enzyme Activation; Enzyme Activation - drug effects; Frogs; Fundamental and applied biological sciences. Psychology; Glucagon; Glucagon - pharmacology; Heart; Heart - physiology; Hepatocytes; Human health and pathology; Isoproterenol; Isoproterenol - pharmacology; Life Sciences; Male; Muscle contraction; Myocytes; Peptides; Phosphodiesterase; Phosphorylation; Physiological effects; Rana esculenta; Rats; Rats, Inbred Strains; Stimulation; Ventricle; Vertebrates: cardiovascular system; Heart; Cardiotonic agent; Pancreatic hormone; Calcium; Glucagon; Rat; Enzyme; Frog; Rodentia; Peptide hormone; Amphibia; Electrophysiology; Patch clamp method; Salientia; Ionic current; Heart rate; Adenylate cyclase; Vertebrata; Mammalia; Cations; Circulatory system; Phosphodiesterase I
• ISSN: 0028-0836; 1476-4687
• DOI: 10.1038/345158a0

Glucagon exerts positive inotropic and chronotropic effects in the heart. Like its glycogenolytic effect in liver cells, the cardiac effects of glucagon are often correlated with adenylyl cyclase stimulation. Therefore, cyclic AMP-dependent phosphorylation of L-type Ca2+ channels might be involved in the inotropic effect of glucagon. There have been no reports, however, of the effects of glucagon on the cardiac Ca2+ current (ICa). Also, the physiological effects of glucagon could involve mechanisms other than stimulation of adenylyl cyclase. Here we show that glucagon enhances ICa in frog and rat ventricular myocytes. The effect of glucagon in rats resulted from a stimulation of adenylyl cyclase. In frogs, however, the effect of glucagon on ICa was smaller and occurred at a concentration tenfold lower than in rats, and adenylyl cyclase was not modified. In addition, cAMP potentiated the effect of glucagon on ICa in frog ventricle, which correlated with the observed inhibition by glucagon of low-Km cAMP phosphodiesterase activity. Therefore, this is an example of a hormone that affects cardiac function in a similar way to a variety of synthetic cardiotonic compounds, such as milrinone and Ro-20-1724. Inhibition of phosphodiesterase activity by glucagon may be essential in animals in which glucagon increases cardiac contractility but does not effectively stimulate adenylyl cyclase.