Involvement of WNK1-mediated potassium channels in the sexual dimorphism of blood pressure

Biochem Biophys Res Commun. 2017 Apr 1;485(2):255-260. doi: 10.1016/j.bbrc.2017.02.098. Epub 2017 Feb 21.


Potassium homeostasis plays an essential role in the control of blood pressure. It is unknown, however, whether potassium balance is involved in the gender-associated blood pressure differences. We therefore investigated the possible mechanism of sexual dimorphism in blood pressure regulation by measuring the blood pressure, plasma potassium, renal actions of potassium channels and upstream regulator in male and female mice. Here we found that female mice exhibited lower blood pressure and higher plasma K+ level as compared to male littermates. Western blot analyses of mouse kidney extract revealed a significant decrease in renal outer medullary potassium (ROMK) channel expression, while large-conductance Ca2+-activated K+ (BK) channel and Na-K-2Cl cotransporter (NKCC2) as well as the upstream regulator with-no-lysine kinase 1 (WNK1) enhanced in female mice under normal condition. Surprisingly, both dietary K+ loading and K+ depletion eliminated the differences in plasma K+ and blood pressure between females and males, and the differences of renal K+ channels and WNK1 also attenuated in both groups of mice. These findings indicated the existence of a close correlation between K+ homeostasis and sex-associated blood pressure. Moreover, the differential regulation of ROMK, BK-α and NKCC2 between female and male mice, at least, were partly mediated via WNK1 pathway, which may contribute to the sexual dimorphism of plasma K+ and blood pressure control.

Keywords: Blood pressure; Gender difference; Large-conductance Ca(2+)-activated K(+) channel; Renal outer medullary potassium; WNK1.

MeSH terms

  • Animals
  • Blood Pressure*
  • Female
  • Kidney / metabolism
  • Large-Conductance Calcium-Activated Potassium Channel alpha Subunits / metabolism*
  • Male
  • Mice, Inbred C57BL
  • Minor Histocompatibility Antigens / metabolism*
  • Potassium / blood
  • Potassium / metabolism
  • Potassium Channels, Inwardly Rectifying / metabolism*
  • Protein Serine-Threonine Kinases / metabolism*
  • Sex Characteristics*
  • Solute Carrier Family 12, Member 1 / metabolism*
  • WNK Lysine-Deficient Protein Kinase 1


  • Kcnj1 protein, mouse
  • Kcnma1 protein, mouse
  • Large-Conductance Calcium-Activated Potassium Channel alpha Subunits
  • Minor Histocompatibility Antigens
  • Potassium Channels, Inwardly Rectifying
  • Slc12a1 protein, mouse
  • Solute Carrier Family 12, Member 1
  • Protein Serine-Threonine Kinases
  • WNK Lysine-Deficient Protein Kinase 1
  • Wnk1 protein, mouse
  • Potassium