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Updated: Aug 5, 2026
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Characterization of G Protein-coupled Receptors by a Fluorescence-based Calcium Mobilization Assay
Published on: July 28, 2014
Molecular model for receptor-stimulated calcium spiking
1Department of Cell Biology, Sherman Fairchild Center, Stanford University School of Medicine, CA 94305.
Summary
Cells exhibit periodic calcium spikes, not sustained rises, when stimulated. A molecular model explains these calcium transients through coupled messengers, inositol 1,4,5-trisphosphate (InsP3) and calcium ions, involving feedback and deactivation.
Area of Science:
- Cellular Biology
- Biochemistry
- Systems Biology
Background:
- Cells often respond to stimuli with periodic calcium spikes rather than a constant increase.
- Understanding the molecular mechanisms driving these calcium oscillations is crucial for cell signaling research.
Purpose of the Study:
- To propose a molecular model explaining periodic calcium spiking induced by constant stimulation.
- To elucidate the key components and processes involved in generating repetitive calcium transients.
Main Methods:
- Development of a molecular model incorporating cooperativity and positive feedback between inositol 1,4,5-trisphosphate (InsP3) and cytosolic calcium ions.
- Inclusion of deactivation and reactivation processes, including InsP3 degradation, calcium reuptake into the endoplasmic reticulum, and mitochondrial sequestration.
- Modeling of bistability and the role of the endoplasmic reticulum calcium store refill rate in setting spike intervals.
Main Results:
- The model demonstrates how cross-coupled messengers (InsP3 and calcium) with cooperativity and positive feedback can generate periodic calcium spikes.
- Mitochondrial sequestration and endoplasmic reticulum refilling are shown to enable system return to basal state and subsequent reactivation, leading to oscillations.
- Calculated spike amplitude, shape, and period align with experimental observations, validating the model's predictive power.
Conclusions:
- The proposed molecular model successfully accounts for periodic calcium spiking observed in stimulated cells.
- Cooperativity, positive feedback, deactivation, and reactivation of InsP3 and calcium signaling are key to generating oscillatory dynamics.
- The model provides a framework for understanding cellular calcium dynamics and its regulation.
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