title: β-Adrenergic regulation of the cardiac Na+-K+ ATPase mediated by oxidative signaling.
abstract: Activation of β-adrenergic receptors (ARs) elicits responses arising from protein kinase A (PKA)-mediated phosphorylation of target proteins that regulate Ca(2+)-dependent excitation-contraction coupling. Some important targets for β-AR- and PKA-dependent pathways, including the sarcolemmal Na(+)-K(+) pump, also undergo oxidative modifications in response to activation of receptor-coupled redox signaling pathways in cardiac myocytes. Here, we highlight how β(1)- and β(3)-AR signaling have opposing effects on functionally important oxidative modification of the Na(+)-K(+) pump molecular complex and how the addition of redox dependence to the canonical phosphorylation dependence of the scheme for β-AR signaling in general expands its versatility but also its complexity. The expanded scheme integrates increased oxidative stress into the pathophysiological effects of adrenergic hyperactivity and provides mechanistic explanation for the efficacy of β-AR blockers in heart failure in which raised intracellular Na(+) levels are detrimental-an explanation not provided by traditionally held views on β-AR-mediated regulation of the pump function.
authors.affiliation: North Shore Heart Research Group, Kolling Institute, University of Sydney, St. Leonards, NSW 2065, Australia.
authors.forename: Keyvan Karimi
authors.initials: KK
authors.lastname: Galougahi
authors.forename: Chia-Chi
authors.initials: CC
authors.lastname: Liu
authors.forename: Henning
authors.initials: H
authors.lastname: Bundgaard
authors.forename: Helge H
authors.initials: HH
authors.lastname: Rasmussen
mesh_terms: D006801:Humans; D032383:Myocytes, Cardiac / Q000201:enzymology*; D018384:Oxidative Stress / Q000502:physiology; D011943:Receptors, Adrenergic, beta / Q000502:physiology*; D015398:Signal Transduction / Q000502:physiology; D000254:Sodium-Potassium-Exchanging ATPase / Q000378:metabolism*
chemical_list: D011943:Receptors, Adrenergic, beta; D000254:Sodium-Potassium-Exchanging ATPase