Dual regulation of calcium mobilization by inositol 1,4,5-trisphosphate ina living cell

Changes in cytosolic free calcium ([Ca2+](i)) often take the form of a sust ained response or repetitive oscillations. The frequency and amplitude of [ Ca2+](i) oscillations are essential for the selective stimulation of gene e xpression and for enzyme activation. However, the mechanism that determines whether [Ca2+](i) oscillates at a particular frequency or becomes a sustai ned response is poorly understood. We find that [Ca2+](i) oscillations in r at megakaryocytes, as in other cells, results from a Ca2+-dependent inhibit ion of inositol 1,4,5-trisphosphate (IP3)induced Ca2+ release. Moreover, we find that this inhibition becomes progressively less effective with higher IP3 concentrations. We suggest that disinhibition, by increasing IP3 conce ntration, of Ca2+-dependent inhibition is a common mechanism for the regula tion of [Ca2+](i) oscillations in cells containing IP3-sensitive Ca2+ store s.