Fig. 4. Block of I_CRAC in ICC with GSK-7975A.

(A) ICC in whole-cell voltage-clamp were held at −50 mV and treated with 0 mM [Ca²⁺]_o solution (solution II) containing NPPB (30 μM) and thapsigargin (1 μM) for 10 min to deplete ER Ca²⁺ and block CaCC. The cells were dialyzed with Cs⁺-rich solution containing BAPTA (solution VI). Reintroduction of 2 mM [Ca²⁺]_o (solution I) activated inward current (I_CRAC). GSK-7975A (10 μM) completely abolished I_CRAC. Ramp potentials from −80 to +60 mV were run during the experiment (examples noted by •, •, and •). (B) Responses to ramp potentials in (A) [• (black trace) is 0 mM [Ca²⁺]_o, • (red trace) is after addition of 2 mM [Ca²⁺]_o, and • (green trace) is after addition of GSK-7975A (10 μM)]. (C) Summary of the effects of GSK-7975A on I_CRAC. Data are means ± SEM [n = 5 cells for each group; ***P < 0.001 compared to 0 mM [Ca²⁺]_o, ###P < 0.001 compared to 2 mM [Ca²⁺]_o, one-way analysis of variance (ANOVA)].