文章基本信息

标题：IP 3-Dependent Ca 2+ Oscillations Switch into a Dual Oscillator Mechanism in the Presence of PLC-Linked Hormones
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作者：Paula J. Bartlett ; Ielyaas Cloete ; James Sneyd 等
期刊名称：iScience
印刷版ISSN：2589-0042
出版年度：2020
卷号：23
期号：5
页码：1-22
DOI：10.1016/j.isci.2020.101062
语种：English
出版社：Elsevier
摘要：SummaryCa2+oscillations that depend on inositol-1,4,5-trisphosphate (IP3) have been ascribed to biphasic Ca2+regulation of the IP3receptor (IP3R) or feedback mechanisms controlling IP3levels in different cell types. IP3uncaging 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 IP3uncaging 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 IP3reproduces 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.Graphical AbstractDisplay OmittedHighlights•Ca2+oscillations driven by IP3R (class 1) and PLC (class 2) occur in the same cell•IP3uncaging 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 stimulationCell Biology; Specialized Functions of Cells; Mathematical Biosciences