GLUCOSE-INDUCED OSCILLATIONS OF BA2+ IN PANCREATIC BETA-CELLS OCCUR WITHOUT INVOLVEMENT OF INTRACELLULAR MOBILIZATION

Ba2+ was used as a substitute for Ca2+ in analyzing the mechanisms responsible for glucose-induced Ca2+ oscillations in pancreatic beta-cells. The 340/380-nm fluorescence excitation ratio was recorded in individual. mouse beta-cells loaded with the indicator fura-a. In 3 mM glucose, Ba2+ entered the cell in a concentration-dependent manner and was partially extruded when the ion was removed from the medium. The extrusion of Ba2+ from the beta-cell was dependent on external Na+, suggesting that Ba2+ can substitute for Ca2+ in Na+/Ca2+ countertransport. When extracellular Ba2+ was kept between 0.3 and 0.5 mM, large amplitude oscillations (0.1-0.4 min(-1)) were induced by glucose at concentrations above 7 mM. The oscillations were often transformed into a sustained elevation either by increase of the glucose or Ba2+ concentrations or by the additions of glucagon, forskolin, or carbachol. Although Ba2+ could substitute for Ca2+ in the glucose-induced large amplitude oscillations, there were no Ca2+-like pronounced spikes superimposed on an elevated cytoplasmic Ba2+ after elevation of cyclic AMP. Neither could Ba2+ substitute for Ca2+ in being incorporated in response to glucose into a pool mobilizable by carbachol. The studies indicate that cations other than Ca2+ can oscillate in response to glucose, and that such oscillations do not require mobilization from internal pools sensitive to inositol 1,4,5-trisphosphate. (C) 1994 Academic Press, Inc. Key