Expression and phosphorylation of the Na-pump regulatory subunit phospholemman in heart failure

Julie B C Bossuyt, Xun Ai, J. Randall Moorman, Steven M. Pogwizd, Donald M Bers

Research output: Contribution to journalArticle

76 Scopus citations

Abstract

Intracellular [Na] is ≈3 mmol/L higher in heart failure (HF; in our arrhythmogenic rabbit model;3), and this can profoundly affect cardiac Ca and contractile function via Na/Ca exchange and Na/H exchange. Na/K-ATPase is the primary mechanism of Na extrusion. We examine here in HF rabbits (and human hearts) expression of Na/K-ATPase isoforms and phospholemman (PLM), a putative Na/K-ATPase regulatory subunit that inhibits pump function and is a major cardiac phosphorylation target. Na/K-ATPase α1- and α2-isoforms were reduced in HF in rabbit ventricular homogenates (by 24%) and isolated myocytes (by 30% and 17%), whereas α3 was increased (50%) in homogenates and decreased (52%) in myocytes (P<0.05). Homogenate Na/K-ATPase activity in left ventricle was also decreased in HF. However, we showed previously that Na/K-ATPase characteristics in intact ventricular myocytes were unaltered in HF. To reconcile these findings, we assessed PLM expression, phosphorylation, and association with Na/K-ATPase. PLM coimmunoprecipitated with Na/K-ATPase α1- and α2 in control and HF rabbit myocytes. PLM expression was reduced in HF by 42% in isolated rabbit left ventricular (LV) myocytes, by 48% in rabbit LV homogenates, and by 24% in human LV homogenate. The fraction of PLM phosphorylated at Ser-68 was increased dramatically in HF. Our results are consistent with a role for PLM analogous to that of phospholamban for SR Ca-ATPase (SERCA): inhibition of Na/K-ATPase function that is relieved on PLM phosphorylation. So reduced Na/K-ATPase expression in HF may be functionally offset by lower inhibition by PLM (because of reduced PLM expression and higher PLM phosphorylation).

Original languageEnglish (US)
Pages (from-to)558-565
Number of pages8
JournalCirculation Research
Volume97
Issue number6
DOIs
StatePublished - Sep 16 2005
Externally publishedYes

Keywords

  • FXYD proteins
  • Heart failure
  • Na/K-ATPase
  • Phospholemman

ASJC Scopus subject areas

  • Physiology
  • Cardiology and Cardiovascular Medicine

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