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Bicarbonate transport drives Na‐independent K secretion (NIKS) via BK‐α/β4 in β‐intercalated cells (IC‐β)
Author(s) -
Cornelius Ryan J,
Hatcher Lori I,
Echtenkamp Kari M,
Contreras Jacob I,
Sansom Steve C
Publication year - 2012
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.26.1_supplement.867.3
Subject(s) - chemistry , urinary system , endocrinology , urine , medicine , secretion , bicarbonate , biochemistry , biology
The Yanomamo tribe, who exemplify NIKS, consume a low Na, high K, alkaline diet and excrete a high volume of urine (control = 9.2 ml/kg/day; Yanomami = 20.7 ml/kg/day) with a low urinary [Cl] (15 mM) and [Na]/[K] (0.007). We hypothesized that the mechanism for NIKS involves KHCO3 secretion via BK‐α/β4 in beta intercalated cells (IC‐β). To test this hypothesis, we fed WT mice (7 d) a low Na (0.01%), high K (5%), alkaline diet (LNaHK). The urinary [Na]/[K] of LNaHK was 0.009 ±0.001, similar to Yanomami. Immunohistochemical analysis of LNaHK kidneys revealed increased V‐ATPase and proportion of IC‐β. The urine pH was 6.3 in control and 8.6 in LNaHK, consistent with the low urinary [Cl] of Yanomami. Mice exhibited a larger increased urinary flow (control = 53 ±5 ml/kg/day, LNaHK = 242 ±19 ml/kg/day), compared with Yanomami. Using this model, we determined whether a knockout of the BK‐β4 (β4KO) exhibited a defect in NIKS. The urinary flow of β4KO on LNaHK was 195 ±17 ml/kg/day, a value slightly lower than WT; however, the trans‐tubular K gradient (TTKG), a measure of Vte‐driven lumen to plasma [K] in the terminal cortical collecting ducts, was 27.5 ±2.0 in WT but reduced to 15.5 ±1.2 in β4KO. When WT were given NH4Cl water with LNaHK diet, the TTKG was reduced to 16.4 ±1.4. Summary: 1. The LNaHK mouse is a good model for NIKS. 2. The activity of BK‐α/β4 is necessary for NIKS. 3. IC‐β activity is enhanced in NIKS. 4. NIKS is inhibited by an acid load.