Ca2+-activated K+ channels mediate duodenal mucosal bicarbonate secretion

Duodenal mucosal bicarbonate secretion (DMBS) is currently accepted as a primary defense process against gastric acid, but the precise mechanism of DMBS has not been completely elucidated. The aim of the present study was to determine whether Ca2+-activated K+(KCa) channels are expressed in the duodenal mucosa and whether they are involved in Ca2+-mediated DMBS. DMBS was determined in vitro by pH-stat and in vivo by using a CO2-sensitive electrode. Expression of KCa in duodenal mucosae was analyzed by RT-PCR. Clotrimazole (30 μM), a selective blocker for intermediate KCa channels (IKCa), significantly inhibited carbachol (CCh)-induced DMBS, but did not affect forskolin-induced or heat-stable enterotoxin of Escherichia coli (STa)-induced DMBS. TRAM-34 (10 μM), another more potent and selective IKCa channel blocker, also significantly inhibited CCh-induced DMBS. However, tetraethylammonium, 4-aminopyridine, and BaCl2, at concentrations known to block K+ channels other than IKCa, failed to inhibit CCh-induce...