THE STORE-OPERATED CALCIUM CURRENT I-CRAC - NONLINEAR ACTIVATION BY INSP(3) AND DISSOCIATION FROM CALCIUM-RELEASE

Patch-clamp experiments aimed at determining the relationship between intracellular Ca2+ release and activation of store-operated calcium cu rrent I-CRAC reveal that both agonist and InsP(3)-mediated activation of I-CRAC are highly nonlinear, occurring over a narrow concentration range. Ca2+ release and Ca2+ influx can be dissociated, as they posses s differential sensitivities to InsP(3): low concentrations induce sub stantial Ca2+ release without any activation of I-CRAC, whereas microm olar concentrations of InsP(3) are required to activate Ca2+ influx. T his suggests functionally distinct stores controlling Ca2+ release and influx and enables cells to switch between sources of Ca2+ to fit bes t their current needs.