Computational Model of Complex Calcium Dynamics: Store Operated Ca²⁺ Channels and Mitochondrial Associated Membranes...

This proposed model explores the intricate Ca²⁺ dynamics within the pancreatic acinar cells (PACs) by emphasizing the role of store-operated Ca²⁺ entry (SOCE) and the mitochondrial-associated membranes (MAMs) in the secretory region (apical) of the PACs. Traditionally, Ca²⁺ releases from the endoplasmic reticulum (ER) via calcium-induced calcium release (CICR). It has been shown to be important in regulating functions such as secretion of digestive enzymes in PACs. However, this model posits that upon the depletion of Ca²⁺ in the ER, the signaling protein stromal interaction molecule (STIM1) is activated. Activated STIM1, then facilitates the opening of Orai channels, allowing Ca²⁺ influx through the store-operated calcium channels (SOCCs). The model highlights the complexity of the Ca²⁺ dynamics, and the importance of SOCE and MAMs in the PACs Ca²⁺ homeostasis. The numerical and bifurcation analysis illustrate how changes in agonist concentrations can lead to the diverse Ca²⁺ oscillation patterns, such as thin to broader oscillations, sinusoidal patterns, and baseline fluctuations, driven by the feedback mechanisms involving Ca²⁺ and inositol 1,4,5 trisphosphate (IP₃). This understanding could have broader implications for cellular physiology and the development of therapies targeting Ca²⁺ signaling pathways.