Effects of verapamil and nifedipine on gliclazide-induced increase in cytosolic free Ca²⁺ in pancreatic islet cells

Abstract

The changes in cytosolic free calcium [Ca²⁺]_i induced by the sulfonylurea gliclazide and potassium in normal rat pancreatic islet cells were measured using the fluorescent Ca²⁺ indicator fura-2. Both in the absence or presence of 5.6 mM glucose, gliclazide caused a rapid and sustained increase in [Ca²⁺]_i. The phenylalkylamine verapamil reduced these increases, but the Ca²⁺ channel blocker was more potent in the presence than in the absence of glucose. In contrast, nifedipine, a Ca²⁺ channel blocker of another chemical type, reduced to a similar extent the increase in [Ca²⁺]_i evoked by gliclazide in the absence and presence of glucose. In the absence of glucose, a rise in extracellular K⁺ concentration from 5 to 20 or 30 mM also induced a rapid and sustained rise in [Ca²⁺]_i. Verapamil more markedly reduced the rise in [Ca²⁺]_i induced by 30 mM than by 20 mM K⁺. It is concluded that gliclazide increases Ca²⁺ inflow into normal islet cells primarily, if not exclusively, by opening voltage-sensitive Ca²⁺ channels. The differential sensitivity toward verapamil of gliclazide-induced rise in [Ca²⁺]_i can be explained by the use-dependent block exerted by Ca²⁺ channel blockers of the phenylalkylamine type.