The present study shows that the calmodulin antagonist calmidazolium inhibited influx of Ca2+ through voltage-gated Ca2+-channels in clonal insulin producing RINm5F-cells. The mechanism of inhibition may involve both Ca2+-calmodulin-dependent protein kinases and direct binding of calmidazolium to the Ca2+-channel. Calmidazolium did not affect uptake of Ca2+ into intracellular Ca2+-pools, inositol 1,4,5-trisphosphate (InsP3) formation or action on intracellular Ca2+-pools. The calmodulin inhibitor also did not affect glucose utilization or oxidation in RINm5F-cells, speaking against an unspecific toxic effect of the compound. KCl-and ATP-stimulated insulin release from RINm5F-cells was attenuated by calmidazolium, whereas basal hormone secretion was unaffected.

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