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Adrenaline‐induced colonic K + secretion is mediated by K Ca 1.1 (BK) channels
Author(s) -
Sørensen Mads V.,
Sausbier Matthias,
Ruth Peter,
Seidler Ursula,
Riederer Brigitte,
Praetorius Helle A.,
Leipziger Jens
Publication year - 2010
Publication title -
the journal of physiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.802
H-Index - 240
eISSN - 1469-7793
pISSN - 0022-3751
DOI - 10.1113/jphysiol.2009.181933
Subject(s) - secretion , bk channel , cystic fibrosis transmembrane conductance regulator , chemistry , apical membrane , endocrinology , ussing chamber , medicine , chloride channel , patch clamp , knockout mouse , potassium channel , biology , cystic fibrosis , receptor , biochemistry , membrane
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, Ca 2+ ‐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 Ca 2+ ‐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 α‐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.