A calcium/cAMP signaling loop at the ORAI1 mouth drives channel inactivation to shape NFAT induction.

The difference in CDI between ORAI1 and ORAI1β, which was highly significant when CRAC currents were activated by including 10 mM of the slow buffer EGTA in the pipette (Fig. 1b–d ) disappeared when CRAC currents were activated by dialysis of 20 mM of the fast chelator BAPTA through the pipette (Fig. 1e–g ) or when extracellular Ca 2+ was replaced by Ba 2+ (Fig. 1h–j ), strongly arguing that this difference in CDI is mediated by cytosolic Ca 2+ at the vicinity of ORAI1 channels.

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