ACTIVATION OF G-PROTEINS INDUCES CA2-CELLS( OSCILLATIONS WITH HYPERPOLARIZING K+ CURRENTS IN PANCREATIC BETA)

Activation of G-proteins by internal perfusion with GTP-gamma-S or ext ernal application of carbachol resulted in oscillations of Ca2+ in iso lated 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 an d disappeared when the cells were internally perfused with 100 mu g/ml heparin. The frequency of the oscillations was positively correlated with the basal level of cytoplasmic Ca2+. Addition of Ca2+ to the inte rnal perfusion medium increased the oscillatory rate and buffering of the ion with Indo-1 or EGTA had the opposite effect. It is concluded t hat G-protein activation results in cyclic mobilisation of intracellul ar 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.