GSK-7975A is described to inhibit stromal interaction molecule 1(STIM1)-mediated Ca²⁺ release-activated Ca²⁺ channels ORAI 1, ORAI 2 and ORAI 3 in different cell types. The present study investigated whether isometric contractions of mouse aortic segments were affected by this selective store-operated calcium channel inhibitor. Depending on the way by which Ca²⁺ influx pathways were activated during contraction, GSK-7975A inhibited contractility of mouse aortic segments with different affinity. When contractile effects were induced by depolarization as with elevated extracellular K⁺ and opening of voltage-gated calcium channels, the affinity was approximately 10 times lower than when contraction was elicited with Ca²⁺ influx via non-selective cation channels. GSK-7975A may repolarize the aortic smooth muscle cells by inhibiting non-selective cation channels, has no effect on IP₃-mediated phenylephrine-induced phasic contractions or on refilling of the contractile sarcoplasmic reticulum Ca²⁺ store, but has significant effects on non-contractile store-operated Ca²⁺ influx.