Calcium release and influx colocalize to the endoplasmic reticulum

Curr Biol. 1997 Aug 1;7(8):599-602. doi: 10.1016/s0960-9822(06)00259-4.


Intracellular Ca2+ is released from intracellular stores in the endoplasmic reticulum (ER) in response to the second messenger inositol (1,4,5) trisphosphate (InsP3) [1,2]. Then, a poorly understood cellular mechanism, termed capacitative Ca2+ entry, is activated [3,4]; this permits Ca2+ to enter cells through Ca(2+)-selective Ca(2+)-release-activated ion channels [5,6] as well as through less selective store-operated channels [7]. The level of stored Ca2+ is sensed by Ca(2+)-permeant channels in the plasma membrane, but the identity of these channels, and the link between them and Ca2+ stores, remain unknown. It has been argued that either a diffusible second messenger (Ca2+ influx factor; CIF) [8] or a physical link [9,10] connects the ER Ca(2+)-release channel and store-operated channels; strong evidence for either mechanism is lacking, however [7,10]. Petersen and Berridge [11] showed that activation of the lysophosphatidic acid receptor in a restricted region of the oocyte membrane results in stimulation of Ca2+ influx only in that region, and concluded that a diffusible messenger was unlikely. To investigate the relationship between ER stores and Ca2+ influx, we used centrifugation to redistribute into specific layers the organelles inside intact Xenopus laevis oocytes, and used laser scanning confocal microscopy with the two-photon technique to 'uncage' InsP3 while recording intracellular Ca2+ concentration. Ca2+ release was localized to the stratified ER layer and Ca2+ entry to regions of the membrane directly adjacent to this layer. We conclude that Ca2+ depletion and entry colocalize to the ER and that the mechanism linking Ca2+ stores to Ca2+ entry is similarly locally constrained.

MeSH terms

  • Animals
  • Calcium / metabolism*
  • Calcium Channels / metabolism
  • Endoplasmic Reticulum / metabolism*
  • Female
  • In Vitro Techniques
  • Inositol 1,4,5-Trisphosphate / metabolism
  • Ion Channel Gating
  • Ion Transport
  • Kinetics
  • Microscopy, Confocal
  • Oocytes / metabolism
  • Second Messenger Systems
  • Xenopus


  • Calcium Channels
  • Inositol 1,4,5-Trisphosphate
  • Calcium