Ischemia-induced phosphorylation of phospholemman directly activates rat cardiac Na/K-ATPase

Fuller, W. , Eeaton, P., Bell, J. R. and Shattock, M. J. (2004) Ischemia-induced phosphorylation of phospholemman directly activates rat cardiac Na/K-ATPase. FASEB Journal, 18(1), pp. 197-199. (doi:10.1096/fj.03-0213fje) (PMID:14597563)

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Regulation of the Na/K ATPase by protein kinases is model-specific. We have observed a profound activation of the sarcolemmal Na/K ATPase during cardiac ischemia, which is masked by an inhibitor of the enzyme in the cytosol. The aim of these studies was to characterize the pathways involved in this activation in the Langendorff-perfused rat heart. Na/K ATPase activity was determined by measuring ouabain-sensitive phosphate generation by cardiac homogenates at 37°C. In isolated sarcolemma, ischemia (30 min) caused a substantial activation of the Na/K ATPase compared with aerobic controls, which was abolished by perfusing the heart with staurosporine or H89. However, the α1 subunit of the Na/K ATPase was not phosphorylated during ischemia. The sarcolemmal protein phospholemman (PLM) was found associated with the Na/K ATPase α1 and β1 but not α2 subunits, and PLM increased its association with the catalytic subunit of PKA following ischemia. In vitro 14-3-3 binding assays indicated that PLM was phosphorylated following ischemia. These results indicate that the ischemia-induced activation of the Na/K ATPase is indirect, through phosphorylation of PLM, which is an integral part of the Na/K ATPase enzyme complex in the heart. The role of PLM is analogous to phospholamban in regulating the sarcoplasmic reticulum calcium ATPase.

Item Type:Articles
Additional Information:This work was supported by grants from the British Heart Foundation and the Wellcome Trust.
Glasgow Author(s) Enlighten ID:Fuller, Dr Will
Authors: Fuller, W., Eeaton, P., Bell, J. R., and Shattock, M. J.
College/School:College of Medical Veterinary and Life Sciences > Institute of Cardiovascular and Medical Sciences
Journal Name:FASEB Journal
Publisher:Federation of American Society of Experimental Biology
ISSN (Online):1530-6860
Published Online:03 November 2003

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