Extracellular potassium dependence of the Na+-K +-ATPase in cardiac myocytes: Isoform specificity and effect of phospholemman

Fei Han, Amy L. Tucker, Jerry B. Lingrel, Sanda Despa, Donald M Bers

Research output: Contribution to journalArticle

34 Scopus citations

Abstract

Cardiac Na+-K+-ATPase (NKA) regulates intracellular Na+, which in turn affects intracellular Ca2+ and contractility via the Na+/Ca2+ exchanger. Extracellular K+ concentration ([K+]) is a central regulator of NKA activity. Phospholemman (PLM) has recently been recognized as a critical regulator of NKA in the heart. PLM reduces the intracellular Na+ affinity of NKA, an effect relieved by PLM phosphorylation. Here we tested whether the NKA α1- vs. α2- isoforms have different external K+ sensitivity and whether PLM and PKA activation affects the NKA affinity for K+ in mouse cardiac myocytes. We measured the external [K+] dependence of the pump current generated by the ouabain-resistant NKA isoform in myocytes from wild-type (WT) mice (i.e., current due to NKA-α1) and mice in which the NKA isoforms have swapped ouabain affinities (α1 is ouabain sensitive and α2 is ouabain resistant) to assess current due to NKA-α2. We found that NKA-α1 has a higher affinity for external K+ than NKA-α2 [half-maximal pump activation (K0.5) = 1.5 ± 0.1 vs. 2.9 ± 0.3 mM]. The apparent external K+ affinity of NKA was significantly lower in myocytes from WT vs. PLM-knockout mice (K0.5 = 2.0 ± 0.2 vs. 1.05 ± 0.08 mM). However, PKA activation by isoproterenol (1 μM) did not alter the K0.5 of NKA for external K+ in WT myocytes. We conclude that 1) NKA-α1 has higher affinity for K + than NKA-α2 in cardiac myocytes, 2) PLM decreases the apparent external K+ affinity of NKA, and 3) phosphorylation of PLM at the cytosolic domain does not alter apparent extracellular K+ affinity of NKA.

Original languageEnglish (US)
JournalAmerican Journal of Physiology - Cell Physiology
Volume297
Issue number3
DOIs
StatePublished - Sep 2009

Keywords

  • Phosphorylation
  • Voltage-clamp

ASJC Scopus subject areas

  • Cell Biology
  • Physiology

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