INHIBITION OF THE ATP-SENSITIVE POTASSIUM CHANNEL BY CLASS-I ANTIARRHYTHMIC AGENT, CIBENZOLINE, IN RAT PANCREATIC BETA-CELLS

1 Cibenzoline, a class I antiarrhythmic agent, was investigated for it s effect on the ATP-sensitive K+ channel of pancreatic beta-cells by t he patch clamp technique. 2 In perforated patch clamp experiments, cib enzoline depolarized the membrane of single beta-cells and thereafter, caused firing of action potentials in the presence of 2.8 mM glucose. 3 Cibenzoline inhibited the activity of the ATP-sensitive K+ channel in cell-attached recordings in the presence of 2.8 mm glucose and evok ed repetitive fluctuations of the baseline current, apparently reflect ing the action potentials of the beta-cell. 4 In whole-cell clamp expe riments, time-independent outward current was induced by depleting cyt oplasmic ATP with 0.1 mm ATP and 0.1 mm ADP in the solution contained in the pipette. The outward current was inhibited by cibenzoline in a dose-dependent manner in the concentration range of 1 muM to 100 muM a nd half maximum inhibition occurred at 1.5 muM. 5 Cibenzoline blocked substantially the ATP-sensitive K+ channel current when applied at the inner side of the membrane in isolated inside-out membrane patches. 6 It is concluded that cibenzoline blocks the ATP-sensitive K+ channel of pancreatic beta-cells and, thereby, stimulates insulin secretion at sub-stimulatory levels of glucose.