Cardiac Function in Mice Overexpressing the β-Adrenergic Receptor Kinase or a βARK Inhibitor

• Published in: Science (American Association for the Advancement of Science) Vol. 268; no. 5215; pp. 1350 - 1353
• Main Authors: Koch, Walter J., Rockman, Howard A., Samama, Philippe, Hamilton, RaeAnn, Bond, Richard A., Milano, Carmelo A., Lefkowitz, Robert J.
• Format: Journal Article
• Language: English
• Published: Washington, DC American Society for the Advancement of Science 02-06-1995; American Association for the Advancement of Science
• Subjects: Adenylyl Cyclases - metabolism; Animals; beta-Adrenergic Receptor Kinases; Biological and medical sciences; Blood Pressure; Cyclic AMP-Dependent Protein Kinases - antagonists & inhibitors; Cyclic AMP-Dependent Protein Kinases - genetics; Cyclic AMP-Dependent Protein Kinases - metabolism; Fundamental and applied biological sciences. Psychology; GTP-Binding Proteins - metabolism; Heart; Heart - physiology; Inurement; Isoproterenol - pharmacology; Isotherms; Mice; Mice, Transgenic; Myocardial Contraction - drug effects; Myocardium - enzymology; P branes; Phenotype; Phosphorylation; Receptors; Receptors, Adrenergic, beta - metabolism; Sarcolemma - enzymology; Systolic pressure; Transgenes; Transgenic animals; Ventricular Pressure; Vertebrates: cardiovascular system; Heart; In vivo; Vertebrata; Cardiac performance; Mammalia; Mouse; Rodentia; Contractility; Transgenic animal; Enzyme inhibitor; Gene overexpression
• ISSN: 0036-8075; 1095-9203
• DOI: 10.1126/science.7761854

Transgenic mice were created with cardiac-specific overexpression of the β-adrenergic receptor kinase-1 (βARK1) or a βARK inhibitor. Animals overexpressing βARK1 demonstrated attenuation of isoproterenol-stimulated left ventricular contractility in vivo, dampening of myocardial adenylyl cyclase activity, and reduced functional coupling of β-adrenergic receptors. Conversely, mice expressing the βARK inhibitor displayed enhanced cardiac contractility in vivo with or without isoproterenol. These animals demonstrate the important role of βARK in modulating in vivo myocardial function. Because increased amounts of βARK1 and diminished cardiac β-adrenergic responsiveness characterize heart failure, these animals may provide experimental models to study the role of βARK in heart disease.