Methods for studying store-operated calcium entry

Methods. 2008 Nov;46(3):204-12. doi: 10.1016/j.ymeth.2008.09.009. Epub 2008 Oct 16.


Activation of surface membrane receptors coupled to phospholipase C results in the generation of cytoplasmic Ca2+ signals comprised of both intracellular Ca2+ release, and enhanced entry of Ca2+ across the plasma membrane. A primary mechanism for this Ca2+ entry process is attributed to store-operated Ca2+ entry, a process that is activated by depletion of Ca2+ ions from an intracellular store by inositol 1,4,5-trisphosphate. Our understanding of the mechanisms underlying both Ca2+ release and store-operated Ca2+ entry have evolved from experimental approaches that include the use of fluorescent Ca2+ indicators and electrophysiological techniques. Pharmacological manipulation of this Ca2+ signaling process has been somewhat limited; but recent identification of key molecular players, STIM and Orai family proteins, has provided new approaches. Here we describe practical methods involving fluorescent Ca2+ indicators and electrophysiological approaches for dissecting the observed intracellular Ca2+ signal to reveal characteristics of store-operated Ca2+ entry, highlighting the advantages, and limitations, of these approaches.

Publication types

  • Review

MeSH terms

  • Animals
  • Calcium / metabolism*
  • Calcium Channels / metabolism
  • Calcium Signaling / drug effects
  • Calcium Signaling / physiology
  • Fluorescent Dyes / pharmacology
  • Humans
  • Inositol 1,4,5-Trisphosphate / metabolism*
  • Receptors, Calcium-Sensing / metabolism
  • Sarcoplasmic Reticulum Calcium-Transporting ATPases / antagonists & inhibitors


  • Calcium Channels
  • Fluorescent Dyes
  • Receptors, Calcium-Sensing
  • Inositol 1,4,5-Trisphosphate
  • Sarcoplasmic Reticulum Calcium-Transporting ATPases
  • Calcium