Simultaneous oscillations of cytoplasmic free Ca²⁺ concentration and Ins(1,4,5)P₃ concentration in mouse pancreatic β-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)P₃ concentration are necessary for this process. We have looked for changes in inositol polyphosphate levels that might occur in suspensions of murine pancreatic β-cells when these cells are induced to display synchronized oscillations in [Ca²⁺](i) by the sequential addition of glucose, an α₂-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⁺]. 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⁺]. oscillations either in β-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.