SIMULTANEOUS OSCILLATIONS OF CYTOPLASMIC FREE CA2+ CONCENTRATION AND INS(1,4,5)P-3, CONCENTRATION IN MOUSE PANCREATIC BETA-CELLS

Changes in the cytoplasmic free Ca2+ concentration ([Ca2+](i)) in stimulated cells are often oscillatory, but the mechanisms that drive these oscillations are still a matter of controversy: different models of the generation of these [Ca2+](i) oscillations make different assumptions as to whether oscillations in Ins(1,4,5)P-3 concentration are necessary for this process. We have looked for I changes in inositol polyphosphate levels that might occur in suspensions of murine pancreatic beta-cells when these cells are induced to display synchronized oscillations in [Ca2+](i) by the sequential addition of glucose, an alpha(2)-adrenergic stimulus and extracellular Ca2+. The intracellular level of Ins(1,4,5)P-3 oscillated in a manner approximately in synchrony with changes in [Ca2+](i). Oscillations in the levels of Ins(1,4,5)P-3 metabolites [Ins(1,3,4)P-3 and inositol bisphosphates] were slightly delayed relative to the Ins(1,4,5)P-3 oscillations, and the concentration of Ins(1,3,4,5,6)P-5 remained approximately constant during the [Ca2+](i) oscillations. These results demonstrate that [Ins(1,4,5)P-3] and [Ca2+](i) oscillate in synchrony in at least one type of cell. Whether such oscillations in intracellular [Ins(1,4,5)P-3] provide a primary driving force for [Ca2+], oscillations either in beta-cells or in other stimulated cells remains to be determined. Even if they do not, the [Ins(1,4,5)P-3] oscillations will at least provide an amplifying influence on the [Ca2+](i) changes.