Activation of G-proteins induces Ca2+ oscillations with hyperpolarizing K+ currents in pancreatic beta-cells.

Activation of G-proteins by internal perfusion with GTP-gamma-S or external application of carbachol resulted in oscillations of cytoplasmic Ca2+ in isolated mouse pancreatic beta-cells. The Ca2+ transients were associated with the generation of K+ currents sufficiently pronounced to induce marked pulses of hyperpolarization. The oscillatory G-protein response remained largely unaffected when altering the membrane potential. The oscillations became less frequent in the presence of 1 mM neomycin and disappeared when the cells were internally perfused with 100 micrograms/ml heparin. The frequency of the oscillations was positively correlated with the basal level of cytoplasmic Ca2+. Addition of Ca2+ to the internal perfusion medium increased the oscillatory rate and buffering of the ion with Indo-1 or EGTA had the opposite effect. It is concluded that G-protein activation results in cyclic mobilisation of intracellular calcium mediated by inositol-1,4,5-triphosphate and that the basal concentration of cytoplasmic Ca2+ is an important determinant for the frequency of the oscillations.