Time course of P2X2R desensitization: experiments and simulations. (A) Patterns of current responses during repetitive agonist application in HEK293 cells bathed in KR buffer. P2X2aR I_max: 3.5 (1), 3.5 (2), 3 (3), and 3.2 (4) nA; P2X2bR I_max: 6.6 (1), 6.5 (2), 6.5 (3), 5 (4), and 4.5 (5) nA. (B) Current simulations (normalized by their maximum amplitudes) obtained using the kinetic model (and default values in Table 1). Currents are generated by repetitively stimulating model cells expressing P2X2aR (left) and P2X2bR (right) three times with 100 µM ATP for 70 s with a washout period of 250 s. P2X2aR I_max: 3.5 (1–3) nA; P2X2bR I_max: 3 (1–3) nA. Repetitive stimulation of both receptors increased desensitization at each consecutive pulse as a result of calcium entry and activation of Ca²⁺-dependent desensitization (i.e., a shift to the bottom row of Fig. 1). The simulations suggest that receptor desensitization is more expressed in P2X2bR as a result of the dominance of L₅ in these receptors.