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Aldosterone up‐regulates K Ca 1.1 (BK) channel‐mediated colonic K + secretion
Author(s) -
Sorensen Mads Vaarby,
Matos Joana E,
Sausbier Matthias,
Ruth Peter,
Praetorius Helle A,
Leipziger Jens
Publication year - 2007
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.21.6.a956-b
Subject(s) - aldosterone , iberiotoxin , bk channel , endocrinology , ionomycin , medicine , secretion , chemistry , potassium channel , epithelial sodium channel , mineralocorticoid receptor , biology , sodium , stimulation , organic chemistry
Potassium secretion is a major determinant of body K + homeostasis. We have shown earlier that K + secretion in mouse distal colon occurs exclusively via luminal Ca 2+ ‐activated K Ca 1.1 (BK) channels. Resting and Ca 2+ ‐sensitive distal colonic K + secretion was completely absent in BK channel α‐subunit knock out mice. Aldosterone is known to enhance colonic K + secretion. Here we investigate if aldosterone stimulated K + secretion occurs via BK channels in mouse distal colon. Luminal Ba 2+ ‐ and iberiotoxin‐sensitive K + secretion was measured in an Ussing chamber. In vitro addition of aldosterone augmented Ba 2+ ‐sensitive K + secretion (ΔIsc(Ba 2+ )) 2‐fold after 2 hours (aldosterone threshold concentration 10 nM). This effect was inhibited by the mineralocorticoid receptor (MR) antagonist spironolactone (1 μM) and the specific BK channel blocker iberiotoxin (120 nM). In vivo aldosterone was augmented via a low Na + diet for 3 weeks. This treatment increased the resting Ba 2+ ‐sensitive short circuit (ΔIsc(Ba 2+ )) 2‐fold. In addition, the K + secretion enhanced via a low Na + diet was blocked by iberiotoxin. In tissues from control and low Na + diet animals, K + secretion could be further activated by luminal ionomycin (1 μM). Importantly, this ionomycin‐stimulated K + secretion was absent in BK α‐subunit knock out mice. In summary, these data confirm that aldosterone MR‐dependently stimulates K + secretion in mouse distal colon and shows that the aldosterone‐elevated K + secretion occurs via an enhanced luminal BK channel conductance.