Synergistic role for P2Y₁₂ receptors through PI3-kinase in the activation of inward cation currents by ADP. Membrane currents and intracellular Ca²⁺ responses were recorded simultaneously at –70 mV in response to 30 μM ADP in control MKs (n = 9) and after exposure to the P2Y₁₂ antagonist AR-C69931MX (1 μM; n = 8) or the PI3-kinase blocker LY294002 (30 μM; n = 5). (A) Timing of the initial ADP-evoked membrane current relative to the intracellular Ca²⁺ increase. (B) Average initial peak ADP-evoked currents. (C) Normalized ADP-evoked Ca²⁺_i peak amplitude (light boxes) and time to peak (dark boxes), expressed as a percentage of control. (D) Frequency of occurrence of repetitive transient inward currents. Error bars represent SEM. *Statistical significance compared with control (saline or ADP, as appropriate) (*P < .05; **P < .01).