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Aldosterone‐dependent and ‐independent effects on renal potassium excretion
Author(s) -
Picard Nicolas,
LoffingCueni Dominique,
Mihailova Marija,
Makhanova Natalia,
Smithies Oliver,
Wagner Carsten,
Loffing Johannes
Publication year - 2008
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.22.1_supplement.934.8
Subject(s) - epithelial sodium channel , medicine , endocrinology , aldosterone , kaliuresis , hyperkalemia , excretion , reabsorption , chemistry , tubular fluid , nephron , apical membrane , kidney , pseudohypoaldosteronism , mineralocorticoid , homeostasis , natriuresis , sodium , biology , biochemistry , organic chemistry , membrane
Aldosterone (aldo) is released from adrenal glands upon potassium (K) loading and hyperkalemia. It stimulates renal K excretion via the ROMK K‐channel and via activation of the apical epithelial sodium channel (ENaC) providing the electrochemical driving force for K secretion. Previous studies using adrenalectomized rodent models showed that both aldo‐dependent and ‐independent effects are important for renal K excretion. Here we characterized a mouse model lacking aldosterone synthase and thus endogenous aldo production. Under basal conditions, KO mice are slightly hyperkalemic but excrete similar quantities of K with urine as WT mice. K loading with food (3% and 5% for 2 days) induced kaliuresis in WT and KO mice. KO mice excreted a 3–4 fold higher volume of diluted urine after 5% K‐loading and were mildly hyperkalemic. Immunohistochemistry revealed that K‐loading (3% K) induced a translocation of ROMK and ENaC from intracellular compartments to the apical membrane of the renal collecting system in WT mice. While the translocation of ENaC was lacking, the translocation of ROMK was even more pronounced in KO mice. Thus, the renal adaptation to K‐loading involves an aldo‐dependent translocation of ENaC and an aldo‐independent translocation of ROMK. This defect is likely compensated by increased apical targeting of ROMK, a higher urinary flow and reduced concentration of urine, which possibly increases flow‐stimulated K secretion and prevents life‐threatening hyperkalemia.