A Dynamic Model of Cytosolic Calcium Concentration Oscillations in Mast Cells

Abstract

In this paper, a dynamic model of cytosolic calcium concentration ([Ca2+]Cyt) oscillations is established for mast cells (MCs). This model includes the cytoplasm (Cyt), endoplasmic reticulum (ER), mitochondria (Mt), and functional region (μd), formed by the ER and Mt, also with Ca2+ channels in these cellular compartments. By this model, we calculate [Ca2+]Cyt oscillations that are driven by distinct mechanisms at varying kdeg (degradation coefficient of inositol 1,4,5-trisphosphate, IP3 and production coefficient of IP3), as well as at different distances between the ER and Mt (ER–Mt distance). The model predicts that (i) Mt and μd compartments can reduce the amplitude of [Ca2+]Cyt oscillations, and cause the ER to release less Ca2+ during oscillations; (ii) with increasing cytosolic IP3 concentration ([IP3]Cyt), the amplitude of oscillations increases (from 0.1 μM to several μM), but the frequency decreases; (iii) the frequency of [Ca2+]Cyt oscillations decreases as the ER–Mt distance increases. What is more, when the ER–Mt distance is greater than 65 nm, the μd compartment has less effect on [Ca2+]Cyt oscillations. These results suggest that Mt, μd, and IP3 can all affect the amplitude and frequency of [Ca2+]Cyt oscillations, but the mechanism is different. The model provides a comprehensive mechanism for predicting cytosolic Ca2+ concentration oscillations in mast cells, and a theoretical basis for calcium oscillations observed in mast cells, so as to better understand the regulation mechanism of calcium signaling in mast cells.