Mechanism of control of Na,K-ATPase in principal cells of the mammalian collecting duct

Ann N Y Acad Sci. 2003 Apr;986:570-8. doi: 10.1111/j.1749-6632.2003.tb07255.x.


The collecting duct is the site of final Na reabsorption according to Na balance requirements. Using isolated rat cortical collecting ducts (CCD) and mpkCCD(cl4) cells, a mouse cortical collecting duct cell line, we have studied the physiological control of Na,K-ATPase, the key enzyme that energizes Na reabsorption. Aldosterone, a major regulator of Na transport by the collecting duct, stimulates Na,K-ATPase activity through both recruitment of intracellular pumps and increased total amounts of Na pump subunits. This effect is observed after a lag time of 1 hour and is independent of Na entry through ENaC, but requires de novo transcription and translation. Vasopressin and cAMP, its second messenger, stimulate Na,K-ATPase activity within minutes through translocation of Na pumps from a brefeldin A-sensitive intracellular pool to the plasma membrane. Dysregulation of collecting duct Na,K-ATPase activity is at least in part responsible of the Na retention observed in nephritic syndrome. In this setting, Na,K-ATPase activity and subunit synthesis are specifically increased in CCD. In conclusion, aldosterone, vasopressin, and intracellular Na control the cell surface expression of Na,K-ATPase and translocation from intracellular stores is a major mechanism of regulation of Na,K-ATPase activity in collecting duct principal cells.

Publication types

  • Review

MeSH terms

  • Aldosterone / pharmacology
  • Aldosterone / physiology*
  • Animals
  • Cyclic AMP / physiology
  • Humans
  • Kidney Tubules, Collecting / enzymology
  • Kidney Tubules, Collecting / physiology*
  • Mammals
  • Models, Biological
  • Nephrotic Syndrome / enzymology
  • Nephrotic Syndrome / physiopathology
  • Sodium / metabolism*
  • Sodium-Potassium-Exchanging ATPase / metabolism*
  • Vasopressins / pharmacology


  • Vasopressins
  • Aldosterone
  • Sodium
  • Cyclic AMP
  • Sodium-Potassium-Exchanging ATPase