Hypertrophy, increased ejection fraction, and reduced Na-K-ATPase activity in phospholemman-deficient mice

Li Guo Jia, Claudia Donnet, Roberta C. Bogaev, Rebecca J. Blatt, Cindy E. McKinney, Kathleen H. Day, Stuart S. Berr, Larry R. Jones, J. Randall Moorman, Kathleen J. Sweadner, Amy L. Tucker

Research output: Contribution to journalArticle

52 Scopus citations

Abstract

Phospholemman (FXYD1), a 72-amino acid transmembrane protein abundantly expressed in the heart and skeletal muscle, is a major substrate for phosphorylation in the cardiomyocyte sarcolemma. Biochemical, cellular, and electrophysiological studies have suggested a number of possible roles for this protein, including ion channel modulator, taurine-release channel, Na +/Ca2+ exchanger modulator, and Na-K-ATPase-associated subunit. We have generated a phospholemman-deficient mouse. The adult null mice exhibited increased cardiac mass, larger cardiomyocytes, and ejection fractions that were 9% higher by magnetic resonance imaging compared with wild-type animals. Notably, this occurred in the absence of hypertension. Total Na-K-ATPase activity was 50% lower in the phospholemman-deficient hearts. Expression (per unit of membrane protein) of total Na-K-ATPase was only slightly diminished, but expression of the minor α2-isoform, which has been specifically implicated in the control of contractility, was reduced by 60%. The absence of phospholemman thus results in a complex response, including a surprisingly large reduction in intrinsic Na-K-ATPase activity, changes in Na-K-ATPase isoform expression, increase in ejection fraction, and increase in cardiac mass. We hypothesize that a primary effect of phospholemman is to modulate the Na-K-ATPase and that its reduced activity initiates compensatory responses.

Original languageEnglish (US)
Pages (from-to)H1982-H1988
JournalAmerican Journal of Physiology - Heart and Circulatory Physiology
Volume288
Issue number4 57-4
DOIs
StatePublished - Apr 2005

Keywords

  • FXYD protein family
  • Heart
  • Knockout
  • Mouse

ASJC Scopus subject areas

  • Physiology

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    Jia, L. G., Donnet, C., Bogaev, R. C., Blatt, R. J., McKinney, C. E., Day, K. H., Berr, S. S., Jones, L. R., Moorman, J. R., Sweadner, K. J., & Tucker, A. L. (2005). Hypertrophy, increased ejection fraction, and reduced Na-K-ATPase activity in phospholemman-deficient mice. American Journal of Physiology - Heart and Circulatory Physiology, 288(4 57-4), H1982-H1988. https://doi.org/10.1152/ajpheart.00142.2004