Abstract
Ca2+ oscillations that depend on inositol-1,4,5-trisphosphate (IP3) have been ascribed to biphasic Ca2+ regulation of the IP3 receptor (IP3R) or feedback mechanisms controlling IP3 levels in different cell types. IP3 uncaging in hepatocytes elicits Ca2+ 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 Ca2+ oscillations elicited by vasopressin. Addition of hormone to cells activated by IP3 uncaging initiates a qualitative transition from high-frequency spatially disorganized Ca2+ transients, to low-frequency, oscillatory Ca2+ waves that propagate throughout the cell. A mathematical model with dual coupled oscillators that integrates Ca2+-induced Ca2+ release at the IP3R and mutual feedback mechanisms of cross-coupling between Ca2+ and IP3 reproduces this behavior. Thus, multiple Ca2+ oscillation modes can coexist in the same cell, and hormonal stimulation can switch from the simpler to the more complex to yield robust signaling.
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•Ca2+ oscillations driven by IP3R (class 1) and PLC (class 2) occur in the same cell•IP3 uncaging elicits brief and often spatially localized class 1 Ca2+ oscillations•GPCRs elicit whole-cell Ca2+ oscillations and waves via a hybrid class 2 mechanism•Dual Ca2+ feedback on IP3R and PLC ensures a robust response to hormonal stimulation
Cell Biology; Specialized Functions of Cells; Mathematical Biosciences