A Dynamic Model of Calcium Frequency Modulation by Mitochondrial Superoxide

Numerous studies have highlighted the crucial roles of cytosolic calcium transients mediated by inositol 1,4,5-trisphosphate receptor (IP3R) channels in intracellular signaling, as well as the significant modulatory effects of cytosolic redox state on these dynamics. Accordingly, developing a mathematical model that captures the core dynamics by which redox state of IP3Rs influence calcium signaling would provide a valuable foundation for simulating and predicting experimental observations. In this study, we developed a dynamic system, based on ordinary differential equations that incorporates a kinetic model for the redox dynamic of the IP3R and the role of this dynamic on the channels gating parameters. Using this framework, we simulated both the static and dynamic effects of mitochondria-derived superoxide fluctuations on local calcium oscillations. Numerical solutions demonstrated that the model quantitatively reproduced experimentally observed changes in local calcium oscillation frequency in response to mitochondria-derived superoxide variations. Overall, the proposed model offers a predictive tool for exploring how redox perturbations affect cellular signaling pathways through calcium frequency modulation.