title: ATP-sensitive K(+) channels in rat colonic epithelium.
abstract: ATP-sensitive K(+) (KATP) channels couple the metabolic state of a cell to its electrical activity. They consist of a hetero-octameric complex with pore-forming Kir6.x (Kir6.1, Kir6.2) and regulatory sulfonylurea receptor (SUR) subunits. Functional data indicate that KATP channels contribute to epithelial K(+) currents at colonic epithelia. However, their molecular identity and their properties are largely unknown. Therefore, changes in short-circuit current (I sc) induced by the KATP channel opener pinacidil (5 10(-4) mol l(-1)) were measured in Ussing chambers under control conditions and in the presence of different blockers of KATP channels. The channel subunits expressed by the colonic epithelium were identified by immunohistochemistry and by RT-PCR. The K(+) channel opener, when administered at the serosal side, induced an increase in I sc consistent with the induction of transepithelial Cl(-) secretion after activation of basolateral K(+) channels, whereas mucosal administration of pinacidil resulted in a negative I sc. The increase in I sc evoked by serosal pinacidil was inhibited by serosal administration of glibenclamide (5 10(-4) mol l(-1)) and gliclazide (10(-6) mol l(-1)), but was resistant even against a high concentration (10(-2) mol l(-1)) of tolbutamide. In contrast, none of these inhibitors (administered at the mucosal side) reduced significantly the negative I sc induced by mucosal pinacidil. Instead, pinacidil inhibited Cl(-) currents across apical Cl(-) channels in basolaterally depolarized epithelia indicating that the negative I sc induced by mucosal pinacidil is due to a transient inhibition of Cl(-) secretion. In mRNA prepared from isolated colonic crypts, messenger RNA for both pore-forming subunits, Kir6.1 and Kir6.2, and two regulatory subunits (SUR1 and SUR2B) was found. Expression within the colonic epithelium was confirmed for these subunits by immunohistochemistry. In consequence, KATP channels are present in the basolateral membrane of the colonic epithelium; their exact subunit composition, however, has still to be revealed.
authors.affiliation: Institute for Veterinary Physiology and Biochemistry, Justus-Liebig-University, Frankfurter Str. 100, Giessen, Germany.
authors.forename: Ervice
authors.initials: E
authors.lastname: Pouokam
authors.forename: Sandra
authors.initials: S
authors.lastname: Bader
authors.forename: Brigitta
authors.initials: B
authors.lastname: Brück
authors.forename: Bärbel
authors.initials: B
authors.lastname: Schmidt
authors.forename: Martin
authors.initials: M
authors.lastname: Diener
mesh_terms: D000818:Animals; D002712:Chlorides / Q000378:metabolism; D003106:Colon / Q000166:cytology / Q000378:metabolism* / Q000502:physiology; D007413:Intestinal Mucosa / Q000378:metabolism* / Q000502:physiology; D017136:Ion Transport; D054086:KATP Channels / Q000235:genetics / Q000378:metabolism*; D020110:Pinacidil / Q000494:pharmacology; D011188:Potassium / Q000378:metabolism; D026902:Potassium Channel Blockers / Q000494:pharmacology; D024661:Potassium Channels, Inwardly Rectifying / Q000235:genetics / Q000378:metabolism*; D051381:Rats; D017208:Rats, Wistar; D064233:Sulfonylurea Receptors / Q000819:agonists / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D000099161:Kcnj11 Channel
chemical_list: D002712:Chlorides; D054086:KATP Channels; D020110:Pinacidil; D011188:Potassium; D026902:Potassium Channel Blockers; D024661:Potassium Channels, Inwardly Rectifying; D064233:Sulfonylurea Receptors; D000099161:Kcnj11 Channel; C092520:uK-ATP-1 potassium channel