The store-operated calcium current I(CRAC): nonlinear activation by InsP3 and dissociation from calcium release

Cell. 1997 Jun 13;89(6):973-80. doi: 10.1016/s0092-8674(00)80282-2.


Patch-clamp experiments aimed at determining the relationship between intracellular Ca2+ release and activation of store-operated calcium current I(CRAC) reveal that both agonist and InsP3-mediated activation of I(CRAC) are highly nonlinear, occurring over a narrow concentration range. Ca2+ release and Ca2+ influx can be dissociated, as they possess differential sensitivities to InsP3: low concentrations induce substantial Ca2+ release without any activation of I(CRAC), whereas micromolar concentrations of InsP3 are required to activate Ca2+ influx. This suggests functionally distinct stores controlling Ca2+ release and influx and enables cells to switch between sources of Ca2+ to fit best their current needs.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Calcium / metabolism*
  • Calcium / pharmacology
  • Calcium Channels / physiology*
  • Enzyme Inhibitors / pharmacology
  • Inositol 1,4,5-Trisphosphate / metabolism
  • Ion Channel Gating / physiology*
  • Leukemia, Basophilic, Acute
  • Nonlinear Dynamics
  • Patch-Clamp Techniques
  • Rats
  • Thapsigargin / pharmacology
  • Tumor Cells, Cultured / chemistry
  • Tumor Cells, Cultured / physiology


  • Calcium Channels
  • Enzyme Inhibitors
  • Thapsigargin
  • Inositol 1,4,5-Trisphosphate
  • Calcium