Aldosterone increases KCa1.1 (BK) channel-mediated colonic K+ secretion.
Mammalian K(+) homeostasis results from highly regulated renal and intestinal absorption and secretion, which balances the unregulated K(+) intake. Aldosterone is known to enhance both renal and colonic K(+) secretion. In mouse distal colon K(+) secretion occurs exclusively via luminal K(Ca)1.1 (BK) channels. Here we investigate if aldosterone stimulates colonic K(+) secretion via BK channels. Luminal Ba(2+) and iberiotoxin (IBTX)-sensitive electrogenic K(+) secretion was measured in Ussing chambers. In vivo aldosterone was augmented via a high K(+) diet. High K(+) diet led to a 2-fold increase of luminal Ba(2+) and IBTX-sensitive short-circuit current in distal mouse colonic mucosa. This effect was absent in BK alpha-subunit-deficient (BK(-/-)) mice. The resting and diet-induced K(+) secretion was stimulated by luminal ionomycin. In BK(-/-) mice luminal ionomycin did not stimulate K(+) secretion. In vitro addition of aldosterone likewise triggered a 2-fold increase in K(+) secretion, which was inhibited by the mineralocorticoid receptor antagonist spironolactone and the BK channel blocker IBTX. Semi-quantification of mRNA from colonic crypts showed up-regulation of BK alpha- and beta(2)-subunits in high K(+) diet mice. The BK channel could be detected luminally in colonic crypt cells by immunohistochemistry. The expression level of the channel in the luminal membrane was strongly up-regulated in K(+)-loaded animals. Taken together, these data strongly suggest that aldosterone-induced K(+) secretion occurs via increased expression of luminal BK channels.
Sørensen
Mads V
MV
Institute of Physiology and Biophysics, The Water and Salt Research Center, University of Aarhus, 8000 Aarhus C, Denmark.
Matos
Joana E
JE
Sausbier
Matthias
M
Sausbier
Ulrike
U
Ruth
Peter
P
Praetorius
Helle A
HA
Leipziger
Jens
J
D000450:Aldosterone / Q000097:blood / Q000378:metabolism* / Q000494:pharmacology; D000818:Animals; D001464:Barium / Q000494:pharmacology; D003106:Colon / Q000187:drug effects / Q000378:metabolism*; D005260:Female; D017353:Gene Deletion; D005786:Gene Expression Regulation; D007150:Immunohistochemistry; D015759:Ionomycin / Q000494:pharmacology; D007476:Ionophores / Q000494:pharmacology; D051037:Large-Conductance Calcium-Activated Potassium Channel alpha Subunits / Q000235:genetics / Q000378:metabolism*; D008297:Male; D051379:Mice; D000451:Mineralocorticoid Receptor Antagonists / Q000494:pharmacology; D010455:Peptides / Q000494:pharmacology; D016133:Polymerase Chain Reaction; D011188:Potassium / Q000008:administration & dosage / Q000494:pharmacology*; D013148:Spironolactone / Q000494:pharmacology; D015854:Up-Regulation
D007476:Ionophores; C465449:Kcnma1 protein, mouse; D051037:Large-Conductance Calcium-Activated Potassium Channel alpha Subunits; D000451:Mineralocorticoid Receptor Antagonists; D010455:Peptides; D001464:Barium; D013148:Spironolactone; D000450:Aldosterone; D015759:Ionomycin; C064719:iberiotoxin; D011188:Potassium