Ca²⁺ signalling in the endoplasmic reticulum/secretory granule microdomain

Cell Calcium. 2015 Oct;58(4):397-404. doi: 10.1016/j.ceca.2015.01.006. Epub 2015 Jan 25.


In 1992, Ca(2+) microdomains were shown to exist in presynaptic nerve terminals. Soon thereafter, in 1993, Ca(2+) 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 Ca(2+) signalling is of crucial physiological significance because of the need to exercise precise control of the exocytotic secretory events. Local Ca(2+) signalling in the apical domain occurs by repetitive episodes of Ca(2+) 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 Ca(2+) store. Thus Ca(2+) release from the small volume of the apical ER terminals can be sustained by intra-ER Ca(2+) diffusion from the basal to the apical parts of the cells. In this short review the particular characteristics of the apical Ca(2+) signalling domain will be discussed with special emphasis on its passive and active Ca(2+) buffering properties and its ability to respond to local Ca(2+) elevations by Ca(2+)-induced Ca(2+) release. The functional significance of these characteristics for appropriate Ca(2+) spiking are discussed as well as the pathophysiological consequences of destroying the Ca(2+) signalling microdomain.

Keywords: Ca(2+) buffering; Ca(2+) signal localization; Ca(2+) spiking; Ca(2+) spreading.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Animals
  • Calcium / metabolism*
  • Calcium Signaling / physiology*
  • Endoplasmic Reticulum / metabolism*
  • Exocytosis / physiology*
  • Humans
  • Pancreas / metabolism
  • Secretory Vesicles / metabolism*


  • Calcium