A Dynamic Model of Cytosolic Calcium Concentration Oscillations in Mast Cells

oleh: Mingzhu Sun, Yingchen Li, Wei Yao

Format: Article
Diterbitkan: MDPI AG 2021-09-01

Deskripsi

In this paper, a dynamic model of cytosolic calcium concentration (<inline-formula><math xmlns="http://www.w3.org/1998/Math/MathML" display="inline"><semantics><mrow><msub><mrow><msup><mrow><mrow><mo>[</mo><mi>Ca</mi></mrow></mrow><mrow><mrow><mn>2</mn><mo>+</mo></mrow></mrow></msup><mo stretchy="false">]</mo></mrow><mrow><mi>Cyt</mi></mrow></msub></mrow></semantics></math></inline-formula>) 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 <inline-formula><math xmlns="http://www.w3.org/1998/Math/MathML" display="inline"><semantics><mrow><msup><mrow><mi>Ca</mi></mrow><mrow><mrow><mn>2</mn><mo>+</mo></mrow></mrow></msup></mrow></semantics></math></inline-formula> channels in these cellular compartments. By this model, we calculate <inline-formula><math xmlns="http://www.w3.org/1998/Math/MathML" display="inline"><semantics><mrow><msub><mrow><msup><mrow><mrow><mo>[</mo><mi>Ca</mi></mrow></mrow><mrow><mrow><mn>2</mn><mo>+</mo></mrow></mrow></msup><mo stretchy="false">]</mo></mrow><mrow><mi>Cyt</mi></mrow></msub></mrow></semantics></math></inline-formula> oscillations that are driven by distinct mechanisms at varying <inline-formula><math xmlns="http://www.w3.org/1998/Math/MathML" display="inline"><semantics><mrow><msub><mi>k</mi><mrow><mi>deg</mi></mrow></msub></mrow></semantics></math></inline-formula> (degradation coefficient of inositol 1,4,5-trisphosphate, <inline-formula><math xmlns="http://www.w3.org/1998/Math/MathML" display="inline"><semantics><mrow><msub><mrow><mi>IP</mi></mrow><mn>3</mn></msub></mrow></semantics></math></inline-formula> and production coefficient of <inline-formula><math xmlns="http://www.w3.org/1998/Math/MathML" display="inline"><semantics><mrow><msub><mrow><mi>IP</mi></mrow><mn>3</mn></msub></mrow></semantics></math></inline-formula>), 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 <inline-formula><math xmlns="http://www.w3.org/1998/Math/MathML" display="inline"><semantics><mrow><msub><mrow><msup><mrow><mrow><mo>[</mo><mi>Ca</mi></mrow></mrow><mrow><mrow><mn>2</mn><mo>+</mo></mrow></mrow></msup><mo stretchy="false">]</mo></mrow><mrow><mi>Cyt</mi></mrow></msub></mrow></semantics></math></inline-formula> oscillations, and cause the ER to release less <inline-formula><math xmlns="http://www.w3.org/1998/Math/MathML" display="inline"><semantics><mrow><msup><mrow><mi>Ca</mi></mrow><mrow><mrow><mn>2</mn><mo>+</mo></mrow></mrow></msup></mrow></semantics></math></inline-formula> during oscillations; (ii) with increasing cytosolic <inline-formula><math xmlns="http://www.w3.org/1998/Math/MathML" display="inline"><semantics><mrow><msub><mrow><mi>IP</mi></mrow><mn>3</mn></msub></mrow></semantics></math></inline-formula> concentration (<inline-formula><math xmlns="http://www.w3.org/1998/Math/MathML" display="inline"><semantics><mrow><msub><mrow><msub><mrow><mrow><mo>[</mo><mi>IP</mi></mrow></mrow><mn>3</mn></msub><mo stretchy="false">]</mo></mrow><mrow><mi>Cyt</mi></mrow></msub></mrow></semantics></math></inline-formula>), the amplitude of oscillations increases (from 0.1 μM to several μM), but the frequency decreases; (iii) the frequency of <inline-formula><math xmlns="http://www.w3.org/1998/Math/MathML" display="inline"><semantics><mrow><msub><mrow><msup><mrow><mrow><mo>[</mo><mi>Ca</mi></mrow></mrow><mrow><mrow><mn>2</mn><mo>+</mo></mrow></mrow></msup><mo stretchy="false">]</mo></mrow><mrow><mi>Cyt</mi></mrow></msub></mrow></semantics></math></inline-formula> 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 <inline-formula><math xmlns="http://www.w3.org/1998/Math/MathML" display="inline"><semantics><mrow><msub><mrow><msup><mrow><mrow><mo>[</mo><mi>Ca</mi></mrow></mrow><mrow><mrow><mn>2</mn><mo>+</mo></mrow></mrow></msup><mo stretchy="false">]</mo></mrow><mrow><mi>Cyt</mi></mrow></msub></mrow></semantics></math></inline-formula> oscillations. These results suggest that Mt, μd, and <inline-formula><math xmlns="http://www.w3.org/1998/Math/MathML" display="inline"><semantics><mrow><msub><mrow><mi>IP</mi></mrow><mn>3</mn></msub></mrow></semantics></math></inline-formula> can all affect the amplitude and frequency of <inline-formula><math xmlns="http://www.w3.org/1998/Math/MathML" display="inline"><semantics><mrow><msub><mrow><msup><mrow><mrow><mo>[</mo><mi>Ca</mi></mrow></mrow><mrow><mrow><mn>2</mn><mo>+</mo></mrow></mrow></msup><mo stretchy="false">]</mo></mrow><mrow><mi>Cyt</mi></mrow></msub></mrow></semantics></math></inline-formula> oscillations, but the mechanism is different. The model provides a comprehensive mechanism for predicting cytosolic <inline-formula><math xmlns="http://www.w3.org/1998/Math/MathML" display="inline"><semantics><mrow><msup><mrow><mi>Ca</mi></mrow><mrow><mrow><mn>2</mn><mo>+</mo></mrow></mrow></msup></mrow></semantics></math></inline-formula> 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.