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

ABSTRACT

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.