Dependency of current amplitudes on [Ca²⁺]_e and free BzATP agonist concentrations, as determined by the kinetic model, Eqs. 1–9. (A) Stimulating the kinetic model with 100 µM BzATP at three levels of [Ca²⁺]_e, 0.5, 2, and 10 mM in the presence of 1 mM Mg²⁺, shows a decrease in current amplitude during [Ca²⁺]_e increase. (B) Best fit to the [Ca²⁺]_e-dependent (left) and free BzATP–dependent (right) dose–response curves of current amplitudes, obtained from stimulating a heterogeneous population of 10 model cells (each generated by randomly selecting parameter values from the distributions listed in Table S1) with 100 µM BzATP. The [Ca²⁺]_e-dependent dose–response curve is a decreasing Hill function, whereas the free BzATP–dependent dose–response curve is an increasing Hill function. (C) As in Fig. 3 E, current amplitudes obtained from stimulating the kinetic model with identical free BzATP concentrations, achieved by variable BzATP and [Ca²⁺]_e, decrease with [Ca²⁺]_e increase. (D) As in Fig. 3 F, current amplitudes obtained from a heterogeneous population of 10 model cells exhibit a decrease with [Ca²⁺]_e during stimulation with identical concentrations of free BzATP in each simulation. Error bars indicate mean ± SEM values of current amplitude.