GPCR mediated control of calcium dynamics: A systems perspective

Area of Science:

• Biochemistry and Pharmacology
• Computational Biology
• Systems Biology

Background:

• G-protein coupled receptor (GPCR) mediated calcium (Ca2+) signaling is vital for complex diseases like neurodegeneration and heart failure.
• Existing reviews lack an integrated view of mathematical models for GPCR signal transduction and dose-response relationships.
• Understanding GPCR-mediated Ca2+ dynamics is crucial for therapeutic target identification.

Purpose of the Study:

• To provide the first integrated review of mathematical descriptions for GPCR signal transduction and Ca2+ dynamics.
• To elucidate the biochemical pathways and molecular mechanisms governing GPCR-mediated Ca2+ oscillations.
• To connect agonist concentration encoding in Ca2+ signals across different GPCR pathways (Gαq, Gαs, Gαi/o).

Main Methods:

• Review of existing literature on GPCR signaling networks and mathematical models.
• Presentation of Ordinary Differential Equation (ODE) formulations for various signaling models.
• Analysis of network motifs and feedback loops controlling intracellular Ca2+ oscillations.
• Compilation of dose-response curves from Ca2+ spiking data for different GPCR pathways.

Main Results:

• Detailed schematics of GPCR signaling networks and their ODE formulations are presented.
• Network motifs are identified to provide insights into agonist-mediated Ca2+ dynamics.
• The interplay of positive and negative feedback loops in controlling Ca2+ oscillations is highlighted.
• Examples of dose-response curves for various GPCR pathways are reviewed.

Conclusions:

• This review offers a systems perspective on GPCR-mediated Ca2+ dynamics, integrating mathematical and experimental findings.
• It facilitates a deeper understanding of how agonist concentrations are translated into Ca2+ signals.
• The findings are valuable for pharmacologists and computational biologists in designing GPCR-targeting drugs for clinical applications.