Potassium modulates electrolyte balance and blood pressure through effects on distal cell voltage and chloride

Cell Metab. 2015 Jan 6;21(1):39-50. doi: 10.1016/j.cmet.2014.12.006.

Abstract

Dietary potassium deficiency, common in modern diets, raises blood pressure and enhances salt sensitivity. Potassium homeostasis requires a molecular switch in the distal convoluted tubule (DCT), which fails in familial hyperkalemic hypertension (pseudohypoaldosteronism type 2), activating the thiazide-sensitive NaCl cotransporter, NCC. Here, we show that dietary potassium deficiency activates NCC, even in the setting of high salt intake, thereby causing sodium retention and a rise in blood pressure. The effect is dependent on plasma potassium, which modulates DCT cell membrane voltage and, in turn, intracellular chloride. Low intracellular chloride stimulates WNK kinases to activate NCC, limiting potassium losses, even at the expense of increased blood pressure. These data show that DCT cells, like adrenal cells, sense potassium via membrane voltage. In the DCT, hyperpolarization activates NCC via WNK kinases, whereas in the adrenal gland, it inhibits aldosterone secretion. These effects work in concert to maintain potassium homeostasis.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Animals
  • Blood Pressure / drug effects*
  • Cell Line
  • Chlorides / metabolism
  • Electrolytes / urine*
  • Humans
  • Kidney Tubules, Distal / metabolism
  • Membrane Potentials / drug effects
  • Mice
  • Mice, Inbred BALB C
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Minor Histocompatibility Antigens
  • Potassium / blood
  • Potassium / metabolism
  • Potassium Channels, Inwardly Rectifying / genetics
  • Potassium Channels, Inwardly Rectifying / metabolism
  • Potassium, Dietary / pharmacology*
  • Protein-Serine-Threonine Kinases / genetics
  • Protein-Serine-Threonine Kinases / metabolism
  • Pseudohypoaldosteronism / metabolism
  • Pseudohypoaldosteronism / pathology
  • Sodium Chloride, Dietary / pharmacology
  • Solute Carrier Family 12, Member 3 / deficiency
  • Solute Carrier Family 12, Member 3 / genetics
  • Solute Carrier Family 12, Member 3 / metabolism
  • WNK Lysine-Deficient Protein Kinase 1

Substances

  • Chlorides
  • Electrolytes
  • Kcnj10 (channel)
  • Minor Histocompatibility Antigens
  • Potassium Channels, Inwardly Rectifying
  • Potassium, Dietary
  • Slc12a3 protein, mouse
  • Sodium Chloride, Dietary
  • Solute Carrier Family 12, Member 3
  • Prkwnk4 protein, mouse
  • Stk39 protein, mouse
  • OXSR1 protein, mouse
  • Protein-Serine-Threonine Kinases
  • WNK Lysine-Deficient Protein Kinase 1
  • Wnk1 protein, mouse
  • Potassium