Simultaneous oscillations of cytoplasmic free Ca2+ concentration and Ins(1,4,5)P3 concentration in mouse pancreatic β-cells

Abstract

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)P3 concentration are necessary for this process. We have looked for 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)P3 oscillated in a manner approximately in synchrony with changes in [Ca2+]i. Oscillations in the levels of Ins(1,4,5)P3 metabolites [Ins(1,3,4)P3 and inositol bisphosphates] were slightly delayed relative to the Ins(1,4,5)P3 oscillations, and the concentration of Ins(1,3,4,5,6)P5 remained approximately constant during the [Ca2+]i oscillations. These results demonstrate that [Ins(1,4,5)P3] and [Ca2+]i oscillate in synchrony in at least one type of cell. Whether such oscillations in intracellular [Ins(1,4,5)P3] provide a primary driving force for [Ca2+]i oscillations either in beta-cells or in other stimulated cells remains to be determined. Even if they do not, the [Ins(1,4,5)P3] oscillations will at least provide an amplifying influence on the [Ca2+]i changes.