The relationship ofpotassiumchannel activity to thesecretionofcholecystokinin(CCK) was evaluated in STC-1 cells, an intestinal CCK-secreting cell line. Patch-clamp and 86Rb efflux studies showed that anATP-sensitivepotassiumchannel was endogenously expressed in STC-1 cells. Furthermore,channelsare present in sufficient number to significantly modulate whole cellpotassiumpermeability after either channel activation or closure with diazoxide (100 microM) or disopyramide (200 microM), respectively. Inhibition of channel activity with glucose (5-20 mM) was found to depolarize the plasma membrane, increase cytosolic calcium levels, and stimulate CCK release. Glucose-mediated release of CCK, as well as the increase in cytosolic calcium, was inhibited by the calcium channel blocker diltiazem (10 microM). It is concluded that intestinalsecretionof CCK may be tonically controlled by activity of basally activeATP-sensitive potassium channels, and after inhibition of channel activity, calcium-dependent CCKsecretionis stimulated.