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This Article Full Text Full Text (PDF) Supplemental Data All Versions of this Article: 586/17/4251    most recent jphysiol.2008.156968v1 Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Google Scholar Articles by Sørensen, M. V. Articles by Leipziger, J. PubMed PubMed Citation Articles by Sørensen, M. V. Articles by Leipziger, J. Related Collections Renal and Endocrine

¹ Institute of Physiology and Biophysics, The Water and Salt Research Center, University of Aarhus, 8000 Aarhus C, Denmark
² Pharmacology and Toxicology, Pharmaceutical Institute, University of Tübingen, 72076 Tübingen, Germany

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_Ca1.1 (BK) channels. Here we investigate if aldosterone stimulates colonic K⁺ secretion via BK channels. Luminal Ba²⁺ 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 Ba²⁺ and IBTX-sensitive short-circuit current in distal mouse colonic mucosa. This effect was absent in BK -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 - and β₂-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.

(Received 15 May 2008; accepted after revision 7 July 2008; first published online 10 July 2008)
Corresponding author J. Leipziger: Institute of Physiology and Biophysics, The Water and Salt Research Center, University of Aarhus, 8000 Aarhus C, Denmark.  Email: leip{at}fi.au.dk