Na/K-ATPase-An Integral Player in the Adrenergic Fight-or-Flight Response

Donald M. Bers, Sanda Despa

Research output: Contribution to journalReview articlepeer-review

47 Scopus citations


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 β-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.

Original languageEnglish
Pages (from-to)111-118
Number of pages8
JournalTrends in Cardiovascular Medicine
Issue number4
StatePublished - May 2009

Bibliographical note

Funding Information:
Supported by grants from the National Institutes of Health HL-81526 and HL-64724 (DMB) and American Heart Association (0735084N to SD).

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine


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