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

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.