Premium
Mediation of Na‐independent K secretion by intercalated cell BK‐α/β4
Author(s) -
Hatcher Lori,
Grimm P. Richard,
Cornelius Ryan J.,
Holtzclaw J. David,
Sansom Steven C.
Publication year - 2011
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.25.1_supplement.1041.3
Subject(s) - medicine , endocrinology , amiloride , chemistry , secretion , sodium , epithelial sodium channel , nephron , biology , kidney , organic chemistry
In the classic mode of K secretion, K is exchanged for reabsorbing Na in the distal nephron. However, Paleolithic humans consumed an alkaline diet of low Na, high K content, indicating a mechanism of Na independent K secretion. We used BK‐β4 knock‐out mice (β4KO) to test the hypothesis that BK‐α/β4 channels, localized in intercalated cells, are utilized to secrete K with HCO3 in a Na‐independent manner. We found that the plasma [K] of wild type mice (WT) increased from a normal diet (0.32%Na + 0.6%K) value of 4.02 to a value of 4.33 when placed on a low Na (0.01%), normal K, diet for 10 days. However, plasma [K] of β4KO increased from 4.05 to 4.75 on a low Na diet, a value significantly greater than WT, consistent with a defect in Na‐independent K secretion. We then treated WT and β4KO with a normal Na, high K (5%K with equal amounts of Cl, citrate, and carbonate) diet for 10 days and administered the ENaC inhibitor amiloride (5 mg/kg/day via osmotic pump) for the last two days. We found that urinary [Na] to plasma [Na] (UNa/PNa) increased similarly, by approximately 2‐fold, in both WT and β4KO treated with amiloride. However, the urine [K] to plasma [K] ratio (UK/PK) of β4KO was 27.0, a value significantly lower than WT (74.5). These results indicate that BK‐β4 has a role in a Na‐independent mode of K secretion.