Fig. 8.

Inhibitory profile of GSK-7975A on less Ca²⁺-selective or monovalent Orai1 currents. (A and B) Time course of whole cell inward currents at −74 mV maximally activated upon passive store-depletion of HEK293 cells co-expressing CFP-STIM1 with YFP-Orai1 E106D upon perfusion of 10 μM (A) and 100 μM (B) GSK-7975A. (C and D) Corresponding I/V relationships to (A, B: 1, 2) of STIM1/Orai1 E106D currents after maximal store-operated activation (1) and upon addition (2) of 10 μM (C) or 100 μM (D) GSK-7975A. (E) Time course of whole cell inward currents at −74 mV maximally activated upon passive store-depletion of HEK293 cells co-expressing CFP-STIM1 with YFP-Orai1 D110/112/114A upon perfusion of 10 μM GSK-7975A (t = 0 s was shifted to a time-point where currents had already reached their maximum). (F) Time course of whole cell inward currents at −74 mV maximally activated upon passive store-depletion of HEK293 cells co-expressing CFP-STIM1 with YFP-Orai1 in 10 mM Ca²⁺ solution. Afterwards 10 mM Ca²⁺ solution was exchanged by a DVF solution and blocked by 10 μM GSK-7975A. (G) Corresponding I/V relationships to (E: 1, 2) of STIM1/Orai1 D110/112/114A currents after maximal store-operated activation (1) and upon addition (2) of 10 μM GSK-7975A. (H) Corresponding I/V relationships to (F: 1, 2, 3) of maximal activated STIM1/Orai1 current in 10mM Ca²⁺ containing solution (1), DVF solution (2) and upon addition (3) of 10 μM GSK-7975A in DVF solution.