The distribution of the endoplasmic reticulum in living pancreatic acinar cells

Studies on pancreatic acinar cells provided the original evidence for the Ca2+ releasing action of inositol 1,4,5-trisphosphate (IP3). Ironically, this system has presented problems for the general theory that IP3 acts primarily on the endoplasmic reticulum (ER), because the IP3-elicited Ca2+ release occurs in the apical pole, which is dominated by zymogen granules (ZGs) and apparently contains very little ER. Using confocal and two-photon microscopy and a number of different ER-specific fluorescent probes, we have now investigated in detail the distribution of the ER in living pancreatic acinar cells. It turns out that although the bulk of the ER, as expected, is clearly located in the baso-lateral part of the cell, there is significant invasion of ER into the granular pole and each ZG is in fact surrounded by strands of ER. This structural evidence from living cells, in conjunction with recent functional studies demonstrating the high Ca2+ mobility in the ER lumen, provides the framework for a coherent and internally consistent theory for cytosolic Ca2+ signal generation in the apical secretory pole, in which the primary Ca2+ release occurs from ER extensions in the granular pole supplied with Ca2+ from the main store at the base of the cell by the tunnel function of the ER