Dependence of current amplitude and desensitization of P2X2aR and P2X2bR on ATP concentration in the kinetic model. (A) Simulated currents normalized by their maximum amplitudes, and (B) receptor accumulation in Q₁ + Q₂ (black) and Q₃ + Q₄ (gray), obtained during the third stimulation of P2X2aR (left) and P2X2bR (right) with 1, 3.2, 10, 32, and 100 µM ATP for 70 s, as indicated by the gray bars (washout periods are 250 s). Increasing ATP dose increases receptor accumulation in Q₃ + Q₄, which in turn activates the Ca²⁺-dependent desensitization via the state Q₃, leading to an increase in current desensitization in both receptors. Because L₅ is smaller for P2X2aR, simulated P2X2b currents desensitize faster than P2X2a currents, in agreement with experimental observations (Fig. 9).