IP-Dependent Ca Oscillations Switch into a Dual Oscillator Mechanism in the Presence of PLC-Linked Hormones.

Ca oscillations that depend on inositol-1,4,5-trisphosphate (IP) have been ascribed to biphasic Ca regulation of the IP receptor (IPR) or feedback mechanisms controlling IP levels in different cell types. IP uncaging in hepatocytes elicits Ca transients that are often localized at the subcellular level and increase in magnitude with stimulus strength. However, this does not reproduce the broad baseline-separated global Ca oscillations elicited by vasopressin. Addition of hormone to cells activated by IP uncaging initiates a qualitative transition from high-frequency spatially disorganized Ca transients, to low-frequency, oscillatory Ca waves that propagate throughout the cell. A mathematical model with dual coupled oscillators that integrates Ca-induced Ca release at the IPR and mutual feedback mechanisms of cross-coupling between Ca and IP reproduces this behavior. Thus, multiple Ca oscillation modes can coexist in the same cell, and hormonal stimulation can switch from the simpler to the more complex to yield robust signaling.