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

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.