Ca2+ signalling in the endoplasmic reticulum/secretory granule microdomain

In 1992, Ca2+ microdomains were shown to exist in presynaptic nerve terminals. Soon thereafter, in 1993, Ca2+ microdomains were demonstrated in the apical granule containing region of pancreatic acinar cells. The pancreatic acinar cell is specialized for bulk secretion of digestive enzymes and therefore has a relatively large apical micro-domain, dominated by secretory (zymogen) granules, in which Ca2+ signalling is of crucial physiological significance because of the need to exercise precise control of the exocytotic secretory events. Local Ca2+ signalling in the apical domain occurs by repetitive episodes of Ca2+ release from a relatively small volume of endoplasmic reticulum (ER) terminals that are functionally fully connected to the bulk of the ER in the baso-lateral region, which is the quantitatively dominant Ca2+ store. Thus Ca2+ release from the small volume of the apical ER terminals can be sustained by intra-ER Ca2+ diffusion from the basal to the apical parts of the cells. In this short review the particular characteristics of the apical Ca2+ signalling domain will be discussed with special emphasis on its passive and active Ca2+ buffering properties and its ability to respond to local Ca2+ elevations by Ca2+-induced Ca2+ release. The functional significance of these characteristics for appropriate Ca2+ spiking are discussed as well as the pathophysiological consequences of destroying the Ca2+ signalling microdomain. (C) 2015 Elsevier Ltd. All rights reserved.