Colonic mammalian K⁺ secretion is under long term hormonal regulation by aldosterone and short term regulation by different local agonists. The BK channel has previously been identified as the apparently only luminal, secretory K⁺ channel of resting, Ca²⁺-activated and aldosterone-induced distal colonic K⁺ secretion. Agonists (e.g. adrenaline) elevating cAMP are potent activators of distal colonic K⁺ secretion. However, the secretory K⁺ channel responsible for cAMP-induced K⁺ secretion remained to be identified. In this study we used Ussing chamber measurements to identify adrenaline-induced electrogenic K⁺ secretion. In mouse distal colon we found that the adrenaline-induced electrogenic ion secretion is a compound effect of a dominating anion secretion and a smaller electrically opposing K⁺ secretion. Using tissue from either BK^+/+ and BK^-/- or CFTR^+/+ and CFTR^-/- 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 greatly 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 a-subunit splice variants. Importantly, the ZERO variant known to be activated by cAMP is differentially up-regulated in enterocytes from animals on high K⁺ diet. In summary, these results strongly indicate that the adrenaline-induced distal colonic K⁺ secretion is mediated by the BK channel and likely involves aldosterone-induced ZERO splice variant up-regulation.