Calcium entry and the control of calcium oscillations

Biochem Soc Trans. 2003 Oct;31(Pt 5):916-9. doi: 10.1042/bst0310916.


During oscillatory Ca(2+) signals, the agonist-induced enhanced entry of extracellular Ca(2+) plays a critical role in modulating the frequency of the oscillations. Although it was originally assumed that the entry of Ca(2+) under these conditions occurred via the well-known, and apparently ubiquitous, store-operated mechanism, subsequent studies suggested that this was unlikely. It is now known that, in many cell types, a novel non-capacitative Ca(2+)-selective pathway whose activation is dependent on arachidonic acid is responsible, and the channels involved [ARC channels (arachidonate-regulated Ca(2+) channels)] have been characterized. These ARC channels co-exist with the store-operated CRAC channels (Ca(2+)-release-activated Ca(2+) channel) in cells, but each plays a unique and non-overlapping role in Ca(2+) signalling. In particular, it is the ARC channels that are specifically activated at the low agonist concentrations that give rise to oscillatory Ca(2+) signals and provide the predominant mode of Ca(2+) entry under these conditions. The indications are that Ca(2+) entry through the ARC channels increases the likelihood that low concentrations of Ins(1,4,5)P(3) will trigger repetitive Ca(2+) release. At higher agonist concentrations, store-depletion is more complete and sustained resulting in the activation of CRAC channels. At the same time the ARC channels are turned off, resulting in what we have described as a reciprocal regulation of these two distinct Ca(2+) entry pathways.

Publication types

  • Research Support, U.S. Gov't, P.H.S.
  • Review

MeSH terms

  • Animals
  • Arachidonic Acid / metabolism
  • Calcium / metabolism*
  • Humans
  • Inositol 1,4,5-Trisphosphate / metabolism
  • Models, Biological
  • Oscillometry
  • Signal Transduction


  • Arachidonic Acid
  • Inositol 1,4,5-Trisphosphate
  • Calcium