Effect of the GIRK channel blockers on agonist-induced platelet aggregation. Aspirinated, washed human platelets were stimulated with (A) 10 μM ADP, (B) 100 nM 2-MeSADP, (C) 1 μM U46619, (D) 0.05 U/mL thrombin, and (E) 1.0 U/mL thrombin, in the presence of 200 μM SKF38393 (F) at 37° C in a lumi-aggregometer and percent light transmission was recorded. Panel G shows the ability of G_i stimulation to rescue platelet aggregation when stimulated with U46619 in the presence of Ro 31-8220 and the effect of GIRK inhibitors. SCH23390 (200 μM), U50488H (100 μM), or AR-C69931MX (100 nM) were added prior to the addition of the agonist. Fibrinogen (2 mg/mL) was exogenously added to ADP-, 2-MeSADP–, or U46619-stimulated platelets. Arrow indicates the addition of reagents. Data are representative of at least 3 independent experiments performed using platelets from 3 different donors.