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.
Highlights
Published: 19 September 2021In recent years, more and more studies have found that mast cells (MCs) play a major role in the mechanism of acupuncture effect, and substances such as histamine and leukotriene, secreted by mast cells in the process of acupuncture, may be the key factors affecting acupuncture [1]
It has been widely accepted that Ca2+ release-activated Ca2+ (CARC) channels are the main mode of Ca2+ influx in electrically non-excitable cells, including MCs [6]
It is known that ER calcium depletion activates CRAC channels on the plasma membrane, leading to extracellular Ca2+ influx and endoplasmic reticulum Ca2+ supplementation
Summary
More and more studies have found that mast cells (MCs) play a major role in the mechanism of acupuncture effect, and substances such as histamine and leukotriene, secreted by mast cells in the process of acupuncture, may be the key factors affecting acupuncture [1]. MCs are activated by mechanical stimulation, and the Ca2+ concentration in μd can reach more than 10 times that in the cytoplasm, which was enough to activate the mitochondrial MCU channel and allow Ca2+ uptake [23,24,25] This explains why high Ca2+ is observed when global Ca2+ is low. In order to explain the calcium signaling observed in mast cells, and explore the influence of each compartment on oscillations more accurately, a comprehensive dynamic model of [Ca 2+ ]Cyt oscillations is established in this paper This model takes the following cellular compartments into account: plasma membrane (Mem), cytoplasm (Cyt), endoplasmic reticulum (ER), and mitochondria (Mt). The degradation and production of IP3 is added to this model, to investigate the effect of IP3 dynamics on [Ca2+ ]Cyt oscillations
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