Verapamil, a phenylalkylamine Ca2 + channel blocker, inhibits ATP-sensitive K + channels in insulin-secreting cells from rats

Radioisotopic and electrophysiological techniques were used to assess the effects of verapamil, a phenylalkylamine Ca2 + channel blocker, on K + permeability of insulin-secreting cells. Verapamil provoked a concentration-dependent inhibition of 86Rb (42K substitute) outflow from prelabelled and perifused rat pancreatic islets. This property appears to be inherent to the phenylalkylamine Ca2 + channel blockers since gallopamil, a methoxyderivative of verapamil, but not nifedipine, a 1,4-dihydropyridine Ca2 + channel blocker, inhibited 86Rb outflow. The experimental data further revealed that verapamil interacted with a Ca2 + -independent, glucose- and glibenclamide-sensitive modality of 86Rb extrusion. Moreover, verapamil prevented the increase in 86Rb outflow brought about by BPDZ 44; a potent activator of the ATP-sensitive K + channel. Single-channel current recordings by the patch clamp technique confirmed that verapamil elicited a dose-dependent inhibition of the ATP-dependent K + channel. Lastly, under experimental conditions in which verapamil clearly inhibited the ATP-sensitive K + channels, the drug did not affect 45Ca outflow, the cytosolic free Ca2 + concentration or insulin release. It is concluded that the Ca2 + entry blocker verapamil inhibits ATP-sensitive K + channels in pancreatic beta cells. This effect was not associated with stimulation of insulin release [Diabetologia (1997) 40: 1403–1410].