The adrenaline‐induced colonic K + secretion is conducted by the ZERO splice variant of K Ca 1.1 (BK)

Colonic K + secretion in mammals under go long term hormonal‐ and short term regulation by local agonists. The BK channel has previously been identified as the only luminal K + channel in resting, Ca 2+ ‐activated and aldosterone‐induced distal K + secretion. Agonists elevating cAMP are potent activators of colonic K + secretion. The K + channel responsible for cAMP‐induced K + secretion remains to be identified. In this study we used Ussing chambers to identify adrenalin‐induced electrogenic K + secretion. In mouse colon we found that adrenaline‐induced ion secretion is a compound effect of a dominating anion secretion and a smaller electrically opposing K + secretion. Using tissue from either BK or CFTR KO and WT mice we were able to isolate the adrenaline‐induced K + secretion. We found that adrenaline‐induced K + secretion: 1) is absent in BK −/− tissue, 2) is up‐regulated in mice on a high K + diet and 3) is present as sustained positive current in colon from CFTR −/− mice. We also identified that colonic enterocytes express STREX and ZERO C‐terminal BK α‐subunit splice variants. Importantly, the ZERO variant known to be activated by cAMP is differentially up‐regulated in animals on high K + diet. In summary, these results strongly indicate that the adrenalin‐induced distal colonic K + secretion is mediated by the BK channel and likely involves aldosterone‐induced ZERO splice variant up‐regulation.