Bicarbonate promotes BK-α/ß4-mediated K excretion in the renal distal nephron.

ABSTRACT

Ca-activated K channels (BK), which are stimulated by high distal nephron flow, are utilized during high-K conditions to remove excess K. Because BK predominantly reside with BK-ß4 in acid/base-transporting intercalated cells (IC), we determined whether BK-ß4 knockout mice (ß4KO) exhibit deficient K excretion when consuming a high-K alkaline diet (HK-alk) vs. high-K chloride diet (HK-Cl). When wild type (WT) were placed on HK-alk, but not HK-Cl, renal BK-ß4 expression increased (Western blot). When WT and ß4KO were placed on HK-Cl, plasma K concentration ([K]) was elevated compared with control K diets; however, K excretion was not different between WT and ß4KO. When HK-alk was consumed, the plasma [K] was lower and K clearance was greater in WT compared with ß4KO. The urine was alkaline in mice on HK-alk; however, urinary pH was not different between WT and ß4KO. Immunohistochemical analysis of pendrin and V-ATPase revealed the same increases in ß-IC, comparing WT and ß4KO on HK-alk. We found an amiloride-sensitive reduction in Na excretion in ß4KO, compared with WT, on HK-alk, indicating enhanced Na reabsorption as a compensatory mechanism to secrete K. Treating mice with an alkaline, Na-deficient, high-K diet (LNaHK) to minimize Na reabsorption exaggerated the defective K handling of ß4KO. When WT on LNaHK were given NH(4)Cl in the drinking water, K excretion was reduced to the magnitude of ß4KO on LNaHK. These results show that WT, but not ß4KO, efficiently excretes K on HK-alk but not on HK-Cl and suggest that BK-α/ß4-mediated K secretion is promoted by bicarbonaturia.