4.6 Article

Adrenaline-induced colonic K plus secretion is mediated by KCa1.1 (BK) channels

Journal

JOURNAL OF PHYSIOLOGY-LONDON
Volume 588, Issue 10, Pages 1763-1777

Publisher

WILEY
DOI: 10.1113/jphysiol.2009.181933

Keywords

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Funding

  1. Desiree and Niels Ydes Foundation
  2. Danish Medical Research Foundation, DFG [SE460/13-3, SFB621/C9]

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Colonic epithelial K+ secretion is a two-step transport process with initial K+ uptake over the basolateral membrane followed by K+ channel-dependent exit into the lumen. In this process the large-conductance, Ca2+-activated K(Ca)1.1 (BK) channel has been identified as the only apparent secretory K+ channel in the apical membrane of the murine distal colon. The BK channel is responsible for both resting and Ca2+-activated colonic K+ secretion and is up-regulated by aldosterone. Agonists (e.g. adrenaline) that elevate cAMP are potent activators of distal colonic K+ secretion. However, the secretory K+ channel responsible for cAMP-induced K+ secretion remains to be defined. In this study we used the Ussing chamber to identify adrenaline-induced electrogenic K+ secretion. We found that the adrenaline-induced electrogenic ion secretion is a compound effect dominated by anion secretion and a smaller electrically opposing K+ secretion. Using tissue from (i) BK wildtype (BK+/+) and knockout (BK-/-) and (ii) cystic fibrosis transmembrane regulator (CFTR) wildtype (CFTR+/+) and knockout (CFTR-/-) mice we were able to isolate the adrenaline-induced K+ secretion. We found that adrenaline-induced K+ secretion: (1) is absent in colonic epithelia from BK-/- mice, (2) is greatly up-regulated in mice on a high K+ diet and (3) is present as sustained positive current in colonic epithelia from CFTR-/- mice. We identified two known C-terminal BK alpha-subunit splice variants in colonic enterocytes (STREX and ZERO). Importantly, the ZERO variant known to be activated by cAMP is differentially up-regulated in enterocytes from animals on a high K+ diet. In summary, these results strongly suggest that the adrenaline-induced distal colonic K+ secretion is mediated by the BK channel and probably involves aldosterone-induced ZERO splice variant up-regulation.

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