title: Adrenaline-induced colonic K+ secretion is mediated by KCa1.1 (BK) channels.
abstract: 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 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.
authors.affiliation: Department of Physiology and Biophysics, The Water and Salt Research Center, Aarhus University, 8000 Aarhus C, Denmark.
authors.forename: Mads V
authors.initials: MV
authors.lastname: Sørensen
authors.forename: Matthias
authors.initials: M
authors.lastname: Sausbier
authors.forename: Peter
authors.initials: P
authors.lastname: Ruth
authors.forename: Ursula
authors.initials: U
authors.lastname: Seidler
authors.forename: Brigitte
authors.initials: B
authors.lastname: Riederer
authors.forename: Helle A
authors.initials: HA
authors.lastname: Praetorius
authors.forename: Jens
authors.initials: J
authors.lastname: Leipziger
mesh_terms: D000319:Adrenergic beta-Antagonists / Q000494:pharmacology; D000450:Aldosterone / Q000097:blood; D000818:Animals; D003106:Colon / Q000187:drug effects / Q000378:metabolism*; D000242:Cyclic AMP / Q000502:physiology; D019005:Cystic Fibrosis Transmembrane Conductance Regulator / Q000235:genetics; D018076:DNA, Complementary / Q000096:biosynthesis / Q000302:isolation & purification; D015194:Diffusion Chambers, Culture; D004594:Electrophysiology; D020895:Enterocytes / Q000187:drug effects / Q000378:metabolism; D004837:Epinephrine / Q000494:pharmacology*; D007413:Intestinal Mucosa / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D051037:Large-Conductance Calcium-Activated Potassium Channel alpha Subunits / Q000187:drug effects / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D018345:Mice, Knockout; D011188:Potassium / Q000378:metabolism* / Q000494:pharmacology; D026902:Potassium Channel Blockers; D017419:Potassium, Dietary / Q000494:pharmacology; D011433:Propranolol / Q000494:pharmacology; D012313:RNA / Q000096:biosynthesis / Q000302:isolation & purification; D020133:Reverse Transcriptase Polymerase Chain Reaction
chemical_list: D000319:Adrenergic beta-Antagonists; D018076:DNA, Complementary; C465449:Kcnma1 protein, mouse; D051037:Large-Conductance Calcium-Activated Potassium Channel alpha Subunits; D026902:Potassium Channel Blockers; D017419:Potassium, Dietary; D019005:Cystic Fibrosis Transmembrane Conductance Regulator; D000450:Aldosterone; D012313:RNA; D011433:Propranolol; D000242:Cyclic AMP; D011188:Potassium; D004837:Epinephrine