Rapid dephosphorylation of the renal sodium chloride cotransporter in response to oral potassium intake in mice

Kidney Int. 2013 May;83(5):811-24. doi: 10.1038/ki.2013.14. Epub 2013 Feb 27.


A dietary potassium load induces a rapid kaliuresis and natriuresis, which may occur even before plasma potassium and aldosterone (aldo) levels increase. Here we sought to gain insight into underlying molecular mechanisms contributing to this response. After gastric gavage of 2% potassium, the plasma potassium concentrations rose rapidly (0.25 h), followed by a significant rise of plasma aldo (0.5 h) in mice. Enhanced urinary potassium and sodium excretion was detectable as early as spot urines could be collected (about 0.5 h). The functional changes were accompanied by a rapid and sustained (0.25-6 h) dephosphorylation of the NaCl cotransporter (NCC) and a late (6 h) upregulation of proteolytically activated epithelial sodium channels. The rapid effects on NCC were independent from the coadministered anion. NCC dephosphorylation was also aldo-independent, as indicated by experiments in aldo-deficient mice. The observed urinary sodium loss relates to NCC, as it was markedly diminished in NCC-deficient mice. Thus, downregulation of NCC likely explains the natriuretic effect of an acute oral potassium load in mice. This may improve renal potassium excretion by increasing the amount of intraluminal sodium that can be exchanged against potassium in the aldo-sensitive distal nephron.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Administration, Oral
  • Aldosterone / blood
  • Animals
  • Biological Transport
  • Cytochrome P-450 CYP11B2 / deficiency
  • Cytochrome P-450 CYP11B2 / genetics
  • Epithelial Sodium Channels / metabolism
  • Female
  • Kidney / metabolism*
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Natriuresis
  • Phosphorylation
  • Potassium, Dietary / administration & dosage
  • Potassium, Dietary / blood*
  • Potassium, Dietary / urine
  • Receptors, Drug / deficiency
  • Receptors, Drug / genetics
  • Receptors, Drug / metabolism*
  • Solute Carrier Family 12, Member 3
  • Symporters / deficiency
  • Symporters / genetics
  • Symporters / metabolism*
  • Time Factors
  • Water-Electrolyte Balance


  • Epithelial Sodium Channels
  • Potassium, Dietary
  • Receptors, Drug
  • Slc12a3 protein, mouse
  • Solute Carrier Family 12, Member 3
  • Symporters
  • Aldosterone
  • Cytochrome P-450 CYP11B2