REGULATION OF CHOLECYSTOKININ SECRETION BY ATP-SENSITIVE POTASSIUM CHANNELS

The relationship of potassium channel activity to the secretion of cho lecystokinin (CCK) was evaluated in STC-1 cells, an intestinal CCK-sec reting cell line. Patch-clamp and Rb-86 efflux studies showed that an ATP-sensitive potassium channel was endogenously expressed in STC-1 ce lls. Furthermore, chan nels are present in sufficient number to signif icantly modulate whole cell potassium permeability after either channe l activation or closure with diazoxide (100 mu M) or disopyramide (200 mu M), respectively. Inhibition of channel activity with glucose (5-2 0 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 t he calcium channel blocker diltiazem (10 mu M). It is concluded that i ntestinal secretion of CCK may be tonically controlled by activity of basally active ATP-sensitive potassium channels, and after inhibition of channel activity, calcium-dependent CCK secretion is stimulated.