Relation between BK-α/β4-mediated potassium secretion and ENaC-mediated sodium reabsorption

Donghai Wen, Ryan J. Cornelius, Dianelys Rivero-Hernandez, Yang Yuan, Huaqing Li, Alan M. Weinstein, Steven C. Sansom

Research output: Contribution to journalArticle

14 Scopus citations


The large-conductance, calcium-activated BK-α/β4 potassium channel, localized to the intercalated cells of the distal nephron, mediates potassium secretion during high-potassium, alkaline diets. Here we determine whether BK-α/β4-mediated potassium transport is dependent on epithelial sodium channel (ENaC)-mediated sodium reabsorption. We maximized sodium-potassium exchange in the distal nephron by feeding mice a low-sodium, high-potassium diet. Wild-type and BK-β4 knockout mice were maintained on a low-sodium, high-potassium, alkaline diet or a low-sodium, high-potassium, acidic diet for 7-10 days. Wild-type mice maintained potassium homeostasis on the alkaline, but not acid, diet. BK-β4 knockout mice could not maintain potassium homeostasis on either diet. During the last 12 h of diet, wild-type mice on either a regular, alkaline, or an acid diet, or knockout mice on an alkaline diet, were administered amiloride (an ENaC inhibitor). Amiloride enhanced sodium excretion in all wild-type and knockout groups to similar values; however, amiloride diminished potassium excretion by 59% in wild-type but only by 33% in knockout mice on an alkaline diet. Similarly, amiloride decreased the trans-tubular potassium gradient by 68% in wild-type but only by 42% in knockout mice on an alkaline diet. Amiloride treatment equally enhanced sodium excretion and diminished potassium secretion in knockout mice on an alkaline diet and wild-type mice on an acid diet. Thus, the enhanced effect of amiloride on potassium secretion in wild-type compared to knockout mice on the alkaline diet clarify a BK- α/β4-mediated potassium secretory pathway in intercalated cells driven by ENaC-mediated sodium reabsorption linked to bicarbonate secretion.

Original languageEnglish (US)
Pages (from-to)139-145
Number of pages7
JournalKidney International
Issue number1
Publication statusPublished - Jul 2014



  • BK-α/β4
  • ENaC
  • K secretion
  • Na reabsorption
  • TTKG
  • math modeling

ASJC Scopus subject areas

  • Nephrology

Cite this

Wen, D., Cornelius, R. J., Rivero-Hernandez, D., Yuan, Y., Li, H., Weinstein, A. M., & Sansom, S. C. (2014). Relation between BK-α/β4-mediated potassium secretion and ENaC-mediated sodium reabsorption. Kidney International, 86(1), 139-145.