IP3-Dependent Ca2+ Oscillations Switch into a Dual Oscillator Mechanism in the Presence of PLC-Linked Hormones

Paula J. Bartlett, Ielyaas Cloete, James Sneyd, Andrew P. Thomas

Research output: Contribution to journalArticle


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.

Original languageEnglish (US)
Article number101062
Issue number5
StatePublished - May 22 2020

All Science Journal Classification (ASJC) codes

  • General


  • Cell Biology
  • Mathematical Biosciences
  • Specialized Functions of Cells

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