Type 5 Adenylyl Cyclase Disruption Alters Not Only Sympathetic But Also Parasympathetic and Calcium-Mediated Cardiac Regulation

ABSTRACT—In a genetically engineered mouse line with disruption of type 5 adenylyl cyclase (AC5), a major cardiac isoform, there was no compensatory increase in other isoforms of AC in the heart. Both basal and isoproterenol (ISO)-stimulated AC activities were decreased by 30% to 40% in cardiac memb...

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Bibliographic Details
Published in:Circulation research 2003-08, Vol.93 (4), p.364-371
Main Authors: Okumura, Satoshi, Kawabe, Jun-ichi, Yatani, Atsuko, Takagi, Gen, Lee, Ming-Chih, Hong, Chull, Liu, Jing, Takagi, Ikuyo, Sadoshima, Junichi, Vatner, Dorothy E, Vatner, Stephen F, Ishikawa, Yoshihiro
Format: Article
Language:English
Subjects:
Acetylcholine - pharmacology
Adenylyl Cyclases - genetics
Adenylyl Cyclases - metabolism
Animals
Atropine - pharmacology
Binding, Competitive
Biological and medical sciences
Blotting, Western
Calcium - metabolism
Calcium - pharmacology
Calcium Channel Blockers - pharmacology
Calcium Channels - physiology
Cardiotonic Agents - pharmacology
Electrocardiography
Female
Fundamental and applied biological sciences. Psychology
Genotype
Heart
Heart - drug effects
Heart - innervation
Heart - physiology
Heart Rate - physiology
Isoenzymes - genetics
Isoenzymes - metabolism
Isoproterenol - pharmacology
Male
Membrane Potentials - drug effects
Mice
Mice, Inbred C57BL
Mice, Inbred Strains
Mice, Knockout
Muscarinic Antagonists - pharmacology
Myocardium - enzymology
Myocardium - metabolism
Parasympathetic Nervous System - physiology
Potassium Channels - physiology
Receptors, Adrenergic, beta - metabolism
Sympathetic Nervous System - physiology
Vasodilator Agents - pharmacology
Verapamil - pharmacology
Vertebrates: cardiovascular system
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Summary:ABSTRACT—In a genetically engineered mouse line with disruption of type 5 adenylyl cyclase (AC5), a major cardiac isoform, there was no compensatory increase in other isoforms of AC in the heart. Both basal and isoproterenol (ISO)-stimulated AC activities were decreased by 30% to 40% in cardiac membranes. The reduced AC activity did not affect cardiac function (left ventricular ejection fraction [LVEF]) at baseline. However, increases in LVEF after ISO were significantly attenuated in AC5 (P
ISSN:0009-7330
1524-4571
DOI:10.1161/01.RES.0000086986.35568.63