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ATP-sensitive K+ channels in rat colonic epithelium

  • Ion Channels, Receptors and Transporters
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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 (SUR1and 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.

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Acknowledgments

Supported by Deutsche Forschungsgemeinschaft, grant Di 388/11-1.

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Authors and Affiliations

  1. Institute for Veterinary Physiology and Biochemistry, Justus-Liebig-University, Frankfurter Str. 100, Giessen, Germany

    Ervice Pouokam, Sandra Bader, Brigitta Brück, Bärbel Schmidt & Martin Diener

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  1. Ervice Pouokam
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  2. Sandra Bader
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  3. Brigitta Brück
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  5. Martin Diener
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Correspondence to Martin Diener.

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Pouokam, E., Bader, S., Brück, B. et al. ATP-sensitive K+ channels in rat colonic epithelium. Pflugers Arch - Eur J Physiol 465, 865–877 (2013). https://doi.org/10.1007/s00424-012-1207-7

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

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