Modeling the influence of co-localized intracellular calcium stores on the secretory response of bovine chromaffin cells

Catecholamines secretion from chromaffin cells is mediated by a Ca2+ -dependent process in the submembrane space where the exocytotic machinery is located and high-Ca2+ microdomains (HCMDs) are formed by the coordinated activity of a functional triad composed of Ca2+ channels, endoplasmic reticulum (ER) and mitochondria. It has been observed experimentally that subpopulations of cortical mitochondria and ER associate to secretory sites in bovine chromaffin cells. Here, we study the effect of the geometrical distribution of the co-localized cortical organelles both in the formation of HCMDs in the vicinity of Ca2+ channels and on the secretory activity of bovine chromaffin cells in response to a single voltage pulse. Our simulations indicate that co-localized organelles have a dual role in the formation of HCMDs, having, on the one hand, an amplification effect due to the Ca2+-induced Ca2+-release mechanism from the ER and, on the other, acting as physical barriers to Ca2+ diffusion. In addition, our simulations suggest that the increased levels of Ca2+ in the microdomain enhances the secretion of the vesicles co-localized to the Ca2+ channels. As a whole, our results support the idea that the functional triads formed by Ca2+ channels, subplasmalemma ER and mitochondria have a positive effect on the secretion of catecholamines in bovine chromaffin cells.