HMG CoA reductase inhibition reduces sarcolemmal Na+-K+ pump density

David F. Gray, Henning Bundgaard, Peter S. Hansen, Kerrie A. Buhagiar, Anastasia S. Mihailidou, Wendy Jessup, Keld Kjeldsen, Helge H. Rasmussen*

*Corresponding author for this work

Research output: Contribution to journalArticle

30 Citations (Scopus)

Abstract

Objectives: HMG CoA reductase inhibitors reduce cellular availability of mevalonate, a precursor in cholesterol synthesis. Since the cholesterol content of cell membranes is an important determinant of Na+-K+ pump function we speculated that treatment with HMG CoA reductase inhibitors affects Na+-K+ pump activity. Methods: We treated rabbits and rats for 2 weeks with the HMG CoA reductase inhibitor lovastatin and measured Na+-K+ pump current (I(p)) in isolated rabbit cardiac myocytes using the whole cell patch-clamp technique, K-dependent p-nitrophenyl phosphatase (p-NPPase) activity in crude myocardial and skeletal muscle homogenates, and vanadate- facilitated 3H-ouabain binding in intact skeletal muscle samples from rats. Results: Treatment with lovastatin caused statistically significant reductions in I(p), myocardial and skeletal muscle K-dependent p-NPPase activity and 3H-ouabain binding in the myocardium and skeletal muscle. The lovastatin-induced decrease in I(p) was eliminated by parenteral co- administration of mevalonate. However, this was not related to cardiac cholesterol content. Conclusions: Treatment with lovastatin reduces Na+-K+ pump activity and abundance in rabbit and rat sarcolemma. (C) 2000 Elsevier Science B.V.

Original languageEnglish
Pages (from-to)329-335
Number of pages7
JournalCardiovascular Research
Volume47
Issue number2
DOIs
Publication statusPublished - Aug 2000
Externally publishedYes

Keywords

  • Cell culture/isolation
  • Cholesterol
  • Lipid metabolism
  • Membrane transport
  • Na/K-Pump

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