Orai1 W76A and STIM1_1–469 have opposite effects on CDI in the Orai1 Y80A background. All currents were recorded as described in Fig. 1 with 20 mM Ca²⁺_o and the standard 10 mM EGTA internal solution. Bars above traces indicate the native elements present in each condition. (A) Representative currents for WT STIM1 + WT Orai1 (from Fig. 1 A) and WT STIM1 + Orai1 Y80A (from Fig. 3 B in Mullins et al., 2016). (B) Representative currents for STIM1_1–469 + WT Orai1 (from Fig. 1 A) and STIM1_1-469 + Orai1 Y80A. (C) Representative currents for WT STIM1 + Orai1 W76A (from Fig. 4 A) and WT STIM1 + Orai1 W76A Y80A. (D) Summary of the extent of CDI measured for the different conditions. Each point on the summary graph represents the mean ± SEM for n = 5–6 cells. Although both STIM1_1–469 and Orai1 W76A have a residual inactivation phenotype when studied on a WT background (B and C, left; D, open symbols), they modulate CDI in opposite directions in the background of Orai1 Y80A (B and C, right; D, closed symbols).