Journalartikel

Jahr der Veröffentlichung: 2013

Seiten: 865-877

Zeitschrift: Pflügers Archiv European Journal of Physiology

Bandnummer: 465

Heftnummer: 6

ISSN: 0031-6768

eISSN: 1432-2013

DOI Link: https://doi.org/10.1007/s00424-012-1207-7

Verlag: Springer

Abstract: 

ATP-sensitive K+ (K-ATP) 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 K-ATP 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 K-ATP 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 K-ATP 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 (SUR1and SUR2B) was found. Expression within the colonic epithelium was confirmed for these subunits by immunohistochemistry. In consequence, K-ATP channels are present in the basolateral membrane of the colonic epithelium; their exact subunit composition, however, has still to be revealed.

Harvard-Zitierstil: Pouokam, E., Bader, S., Brück, B., Schmidt, B. and Diener, M. (2013) ATP-sensitive K+ channels in rat colonic epithelium, Pflügers Archiv European Journal of Physiology, 465(6), pp. 865-877. https://doi.org/10.1007/s00424-012-1207-7

APA-Zitierstil: Pouokam, E., Bader, S., Brück, B., Schmidt, B., & Diener, M. (2013). ATP-sensitive K+ channels in rat colonic epithelium. Pflügers Archiv European Journal of Physiology. 465(6), 865-877. https://doi.org/10.1007/s00424-012-1207-7