Figure 5.

Effect of cinacalcet on intracellular calcium responses of cells expressing the AP2σ variants Thr112Met, Met117Ile and Glu142Lys. ${\text{Ca}}_{ \mathrm{i}}^{2\text{+}}$ responses, measured by flow cytometry, to changes in [Ca²⁺]_e of HEK-CaSR cells transfected with wild-type (WT) or (A) Thr112Met, (B) Met117Ile or (C) Glu122Gly variants (v) AP2σ proteins. The ${\text{Ca}}_{ \mathrm{i}}^{2\text{+}}$ responses to changes in [Ca²⁺]_e are expressed as a percentage of the maximum normalized responses and shown as the mean±SEM of 4–8 independent transfections. The Thr112Met, Met117Ile and Glu142Gly AP2σ variants led to a rightward shift in the concentration–response curve (red line), compared to WT, and the addition of 10 nm cinacalcet (cin) rectified these rightward shifts of the AP2σ variants (blue line). (D–F) Histograms showing the mean half-maximal concentration (EC₅₀) with 95% confidence intervals (CI) and P-values of cells expressing WT (black bar), (D) Thr112Met, (E) Met117Ile and (F) Glu142Gly variants treated with vehicle (red bars), or treated with 10 nm cinacalcet (blue bars) AP2σ proteins. Statistical analysis was performed using the F-test. ****P < 0.0001, ***P < 0.001 compared to WT.