Role of voltage-dependent Na+ channels for rhythmic Ca2+ signalling in glucose-stimulated mouse pancreatic β-cells

The putative role of voltage dependent Na+ channels for glucose induction of rhythmic Ca2+ signalling was studied in mouse pancreatic beta-cells with the use of the Ca2+ indicator fura-2. A rise in glucose from 3 to 11 mM resulted in slow oscillations of the cytoplasmic Ca2+ concentration ([Ca2+](i)). These oscillations, as well as superimposed transients seen during forskolin-induced elevation of cAMP, remained unaffected in the presence of the Na+ channel blocker tetrodotoxin. During exposure to 1-10 mu M veratridine, which facilitates the opening of voltage dependent Na+ channels, the slow oscillations were replaced by repetitive and pronounced [Ca2+](i) transients arising from the basal level. The effects of veratridine were reversed by tetrodotoxin. The veratridine induced [Ca2+](i) transients were critically dependent on the influx of Ca2+ and persisted after thapsigargin inhibition of the endoplasmic reticulum Ca2+-ATPase. Both tolbutamide and ketoisocaproate mimicked the action of glucose in promoting [Ca2+](i) transients in the presence of veratridine. It is suggested that activation of voltage-dependent Na+ channels is a useful approach for amplifying Ca2+ signals for insulin release. CELL SIGNAL 11;5:343-348, 1999. (C) 1999 Elsevier Science Inc.