Na,K-ATPase as a signal transducer

Ann N Y Acad Sci. 2003 Apr;986:489-96. doi: 10.1111/j.1749-6632.2003.tb07233.x.


Recent studies have indicated that Na,K-ATPase may, in addition to being the key regulator of intracellular Na(+) and K(+) concentration, act as a signal transducer. Despite extensive research, the biological role for ouabain, a natural ligand of Na,K-ATPase, is not well understood. We have reported that exposure of rat proximal tubular cells (RPTC) to doses of ouabain that inhibit the Na,K-ATPase activity by less than 50% (10 nM - 500 micro M), will induce intracellular [Ca(2+)](i) oscillations and that this calcium signal leads to activation of the transcription factor NF-kappaB. The ouabain-induced calcium oscillations were blocked by an inhibitor of the IP(3) receptors but not by phospholipase C inhibitors nor by cellular depletion of IP(3), suggesting that the calcium signal is not due to phospholipase C-mediated IP(3) release. Fluorescence resonance energy transfer (FRET) studies suggested a close proximity between the Na,K-ATPase and IP(3) receptor. Our findings demonstrate a novel principle for calcium signaling via Na,K-ATPase.

MeSH terms

  • Animals
  • Biological Transport, Active
  • Calcium / physiology*
  • Cells, Cultured
  • Kidney Tubules, Proximal / enzymology
  • Kidney Tubules, Proximal / physiology*
  • Kinetics
  • Ouabain / pharmacology
  • Potassium / metabolism
  • Rats
  • Rats, Sprague-Dawley
  • Signal Transduction / physiology*
  • Sodium / metabolism
  • Sodium-Potassium-Exchanging ATPase / metabolism*


  • Ouabain
  • Sodium
  • Sodium-Potassium-Exchanging ATPase
  • Potassium
  • Calcium