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

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 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 hours 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 transtubular 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.