Understanding Calcium Dynamics via Process-Oriented Geometric Singular Perturbation Theory.

We consider a general model for intracellular calcium dynamics. This model has solutions that evolve on multiple timescales, but cannot be written in the so-called standard form for geometric singular perturbation theory (GSPT). We propose a biologically motivated process-based approach for the identification of timescales and small parameters in the model. Using a coordinate-independent formulation of GSPT in combination with the blow-up method, we then prove the existence of relaxation oscillations with three distinct timescales in a certain parameter regime. Finally, we identify both singular and regular Andronov-Hopf bifurcations occurring as a possible mechanism for the onset of the relaxation oscillations under variations of important model parameters.