Computational Model of Complex Calcium Dynamics: Store Operated Ca Channels and Mitochondrial Associated Membranes in Pancreatic Acinar Cells.

This proposed model explores the intricate Ca dynamics within the pancreatic acinar cells (PACs) by emphasizing the role of store-operated Ca entry (SOCE) and the mitochondrial-associated membranes (MAMs) in the secretory region (apical) of the PACs. Traditionally, Ca 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 Ca in the ER, the signaling protein stromal interaction molecule (STIM1) is activated. Activated STIM1, then facilitates the opening of Orai channels, allowing Ca influx through the store-operated calcium channels (SOCCs). The model highlights the complexity of the Ca dynamics, and the importance of SOCE and MAMs in the PACs Ca homeostasis. The numerical and bifurcation analysis illustrate how changes in agonist concentrations can lead to the diverse Ca oscillation patterns, such as thin to broader oscillations, sinusoidal patterns, and baseline fluctuations, driven by the feedback mechanisms involving Ca and inositol 1,4,5 trisphosphate (IP). This understanding could have broader implications for cellular physiology and the development of therapies targeting Ca signaling pathways.