Effect of GIRK channel blockers on G protein–mediated platelet functional responses. (A) Effect of GIRK channel blockers on platelet shape change. Aspirin-treated and washed human platelets were treated with fibrinogen receptor antagonist SC57101A (10 μM) to block aggregation prior to addition of agonist. ADP (10 μM) and 2-MeSADP (100 nM) were added under stirring conditions to observe the shape-change response. SCH23390 (200 μM) and U50488H (100 μM) were added prior to agonist stimulation. (B) Effect of SCH23390 on ADP-mediated platelet intracellular calcium release. Fura-2am–loaded human platelets were activated with 10 μM ADP and 1 μM U46619 in the presence of SC57101A (10 μM) to measure calcium mobilization. (C) Effect of GIRK channel blockers on P2Y₁₂ receptor–mediated inhibition of adenylyl cyclase. Washed, aspirinated, and [³H]-adenine treated and (20 μM) forskolin-stimulated platelets were stimulated with ADP (10 μM) in the presence of AR-C69931MX (100 nM), SCH23390 (200 μM), or U50488H (100 μM) as noted and inhibition of adenylyl cyclase was studied. Data are expressed as percent of total [³H]-adenine nucleotides. Data are representative of 3 independent experiments done using platelets from 3 donors, and error bars indicate SEM.