Sensitivity of pancreatic beta cell to calcium channel blockers. An electrophysiologic study of verapamil and nifedipine.

Abstract

Microelectrodes were used to study the comparative effects of 2 calcium channel blockers on glucose-induced electrical activity in mouse beta cells. In 2.8 mM glucose, verapamil (10(-5) M), but not nifedipine (10(-7) M), induces a silent depolarization. In 11.1 mM glucose, verapamil (10(-7) to 5.10(-5) M) induces continuous spike activity by a decrease in the maximum repolarization potential. Nifedipine (10(-10) to 10(-6) M) induces the same activity, but subsequent to a hyperpolarization of the cell at the maximal repolarization potential followed by a silent phase to the plateau potential. The 2 drugs induce a dose-dependent decrease in spike frequency without any change in spike amplitude. In 22 mM glucose exposure to nifedipine, but not to verapamil, induces a transient period of slow-wave activity. The 2 drugs induce a dose-dependent decrease in spike frequency. At higher concentrations (nifedipine greater than 10(-7) M; verapamil greater than 10(-6) M) they induce the disappearance of spikes through a decrease in amplitude. These results show that the beta cell is more sensitive to nifedipine (ED50 = 3 X 10(-8) M) than to verapamil, and that glucose stimulation increases the cell's sensitivity to verapamil (11.1 mM glucose: ED50 = 10(-5) M versus 5 X 10(-7) M in 22 mM glucose) but not to nifedipine.