Dependence of P2X7R deactivation on [Ca²⁺]_e as determined by the kinetic model, Eqs. 1–9. (A) Repetitive 1-s stimulation with 100 µM BzATP in the presence of 2 mM (left) and in the absence (right) of extracellular Ca²⁺ (compare with Fig. 4 A). (B) Currents from A normalized by their maximum amplitudes show that the deactivation components of these currents are slower in Ca²⁺-deficient medium (gray) than in Ca²⁺-containing medium (black). Slowing of deactivation with each subsequent pulse occurs with or without extracellular Ca²⁺ (compare with Fig. 4 B). (C) Stimulating the kinetic model with 100 µM BzATP for 40 s in the presence (black) and absence (gray) of extracellular Ca²⁺ and normalizing current amplitudes by their maximum values result in both faster sensitization (and pore dilation) and also slower deactivation in the absence of extracellular Ca²⁺ during both the first (left) and second (right) stimulations (compare with Fig. 4 C). (D) Deactivation components normalized by their maximum values during 100-µM BzATP stimulation for 40 s. Decreasing [Ca²⁺]_e from 10 to 5 and then 0.5 mM slows deactivation (left). The slow time constant τ_off2 (right), obtained from fitting biexponential curves to the deactivation curves obtained from stimulating 10 heterogeneous populations of simulated cells, decreases with [Ca²⁺]_e (compare with Fig. 4 D). Error bars indicate mean ± SEM values of (E) Calcium removal during P2X7R deactivation at two disjointed 2-s intervals (left) and one 5-s interval (right) results in slower deactivation (compare with Fig. 4, E and F). Simulated currents were generated for a 40-s application of 100 µM BzATP in the presence of 2-mM [Ca²⁺]_e and normalized by their maximum values.