Dissociation between exocytosis and Ca²⁺-channel activity in mouse pancreatic β-cells stimulated with calmidazolium (compound R24571)

Calmidazolium, a calmodulin inhibitor, suppressed influx of Ca²⁺ through voltage-gated Ca²⁺ channels in mouse pancreatic β-cells. Despite this fact, calmidazolium stimulated insulin release from β-cells at basal glucose concentration. This effect was not mediated by protein kinase C (PKC), since it persisted in PKC-depleted cells. R_pcAMPS significantly attenuated tha calmidazolium-stimulated insulin secretion, indicating that calmidazolium acts, at least partly, through PKA. The compound also stimulated insulin secretion from electropermeabilized β-cells, indicating effects on distal steps in the stimulus-secretion coupling. The use of calmidazolium offers possibilities to investigate the mechanisms activating exocytosis under conditions where the cytoplasmic-free Ca²⁺ concentration does not increase.