The flavonol quercetin activates basolateral K+ channels in rat distal colon epithelium

1 The flavonol quercetin has been shown to activate a Cl- secretion in rat colon. Unlike the secretory activity of the related isoflavone genistein, quercetin's secretory activity does not depend on cyclic AMP; instead, it depends on Ca2+. We investigated the possible involvement of Ca2+ dependent basolateral K+ channels using apically permeabilized rat distal colon epithelium mounted in Ussing chambers. 2 In intact epithelium, quercetin induced an increase in short-circuit current (I-SC), which was diminished by the Cl- channel blockers NPPB and DPC, but not by glibenclamide, DIDS or anthracene-9-carboxylic acid. The effect of the flavonol was also inhibited by several serosally applied K+ channel blockers (Ba2+, quinine, clotrimazole, tetrapentylammonium, 293B), whereas other K+ channel blockers failed to influence the quercetin-induced increase in I-SC (tetraethylammonium, charybdotoxin). 3 The apical membrane was permeabilized by mucosal addition of nystatin and a serosally directed K+ gradient was applied. The successful permeabilization was confirmed by experiments demonstrating the failure of bumetanide to inhibit the carbachol-induced current. 4 In apically permeabilized epithelium, quercetin induced a K+ current (I-K), which was neither influenced by ouabain nor by bumetanide. Whereas DPC, NPPB, charybdotoxin and 293B failed to inhibit this I-K, quinine, Ba2+, clotrimazole and tetrapentylammonium were effective blockers of this current. 5 We conclude from these results that at least part of the quercetin-induced Cl- secretion can be explained by an activation of basolateral K+ channels.