Role of Ca2+-activated K+ channels in duodenal mucosal ion transport and bicarbonate secretion

Stimulation of muscarinic receptors in the duodenal mucosa raises cytosolic free Ca2+ concentration ([Ca2+]cyt), thereby regulating duodenal epithelial ion transport. However, little is known about the downstream molecular targets that account for this Ca2+-mediated biological action. Ca2+-activated K+ (KCa) channels are candidates, but the expression and function of duodenal KCa channels are poorly understood. Therefore, we determined whether KCa channels are expressed in the duodenal mucosa and investigated their involvement in Ca2+-mediated duodenal epithelial ion transport. Two selective blockers of intermediate-conductance Ca2+-activated K+ (IKCa) channels, clotrimazole (30 μM) and 1-[(2-chlorophenyl)diphenylmethyl]-1H-pyrazole (TRAM-34; 10 μM), significantly inhibited carbachol (CCh)-induced duodenal short-circuit current (Isc) and duodenal mucosal bicarbonate secretion (DMBS) in mice but did not affect responses to forskolin and heat-stable enterotoxin of Escherichia coli. Tetraethylammonium, 4-ami...