Na/K-ATPase--an integral player in the adrenergic fight-or-flight response.
During activation of the sympathetic nervous system, cardiac performance is increased as part of the fight-or-flight stress response. The increase in contractility with sympathetic stimulation is an orchestrated combination of intrinsic inotropic, lusitropic, and chronotropic effects, mediated in part by activation of beta-adrenergic receptors and protein kinase A. This causes phosphorylation of several Ca cycling proteins in cardiac myocytes (increasing Ca entry via L-type Ca channels, sarcoplasmic reticulum Ca pumping, and the dissociation rate of Ca from the myofilaments). Here, we discuss how stimulation of the Na/K-ATPase, mediated by phosphorylation of phospholemman (a small sarcolemmal protein that associates with and modulates Na/K-ATPase), is an additional important player in the sympathetic fight-or-flight response. Enhancement of Na/K- ATPase activity limits the rise in [Na](i) caused by the higher level of Na influx and by doing so limits the rise in cellular and sarcoplasmic reticulum Ca load by favoring Ca extrusion via the Na/Ca exchanger. Thus, phospholemman-mediated activation of the Na/K-ATPase may prevent Ca overload and triggered arrhythmias during stress.
Bers
Donald M
DM
Department of Pharmacology, University of California, Davis, CA 95616-8636, USA. dmbers@ucdavis.edu
Despa
Sanda
S
D001145:Arrhythmias, Cardiac / Q000378:metabolism / Q000503:physiopathology / Q000517:prevention & control; D020013:Calcium Signaling; D017868:Cyclic AMP-Dependent Protein Kinases / Q000378:metabolism; D004924:Escape Reaction; D006321:Heart / Q000294:innervation*; D006339:Heart Rate; D006801:Humans; D008565:Membrane Proteins / Q000378:metabolism; D009200:Myocardial Contraction; D009206:Myocardium / Q000201:enzymology*; D010750:Phosphoproteins / Q000378:metabolism; D010766:Phosphorylation; D011943:Receptors, Adrenergic, beta / Q000378:metabolism; D012964:Sodium / Q000378:metabolism; D019831:Sodium-Calcium Exchanger / Q000378:metabolism; D000254:Sodium-Potassium-Exchanging ATPase / Q000378:metabolism*; D013564:Sympathetic Nervous System / Q000378:metabolism*
D008565:Membrane Proteins; D010750:Phosphoproteins; D011943:Receptors, Adrenergic, beta; D019831:Sodium-Calcium Exchanger; C069141:phospholemman; D012964:Sodium; D017868:Cyclic AMP-Dependent Protein Kinases; D000254:Sodium-Potassium-Exchanging ATPase