Ligands of σ1R modulate SOCE. (A–F) Populations of cells were treated with 25 µM (+)SKF10047 or 10 µM BD1047 before removal of extracellular Ca²⁺, addition of 5 µM thapsigargin, and then restoration of extracellular 4 mM Ca²⁺ to CHO (A and B), HEK-σ1R (C and D), or wild-type HEK cells (E and F). Summary results (B, D, and F) show peak increases in [Ca²⁺]_c after restoration of extracellular Ca²⁺. The color codes in A apply to all panels (A–F). (G) Representative immunoblot from CHO cells transfected with control plasmid or plasmid encoding siRNA for σ1R (siσ1R). (H) Summary results show band intensities for the indicated proteins normalized to those from cells treated with control plasmid. (I) Ca²⁺ signals evoked by addition of thapsigargin in Ca²⁺-free HBS and then restoration of extracellular Ca²⁺ in CHO cells treated with siσ1R or control plasmid. (J) Summary shows peak [Ca²⁺]_c after restoration of extracellular Ca²⁺ to thapsigargin-treated CHO cells treated with siσ1R or control plasmid. Cells were pretreated with 25 µM (+)SKF10047 or 10 µM BD1047, as indicated. (K and L) Effects of siσ1R or control plasmid and pretreatment with σ1R ligands on the Ca²⁺ signals evoked by 5 µM ionomycin in Ca²⁺-free HBS. Typical traces (K) and summary results (L) are shown. Legends for L are the same as J. All summary results show mean ± SEM. n = 3. *, P < 0.05; **, P < 0.01; ***, P < 0.001. ANOVA with Tukey’s posthoc analysis (B, D, F, J, and L) or Student’s t test (H and comparison of no treatment conditions in J and L).