Reactions and parameter values used in this study.

Values for the kinetic parameters and network structure were taken from the literature or estimated from experimental data. The kinetics of binding and catalytic interactions were assumed to follow mass-action rate laws. The quantity denotes forward rate constants, denotes backward rate constants and denotes catalytic rate constants. All binding interactions were assumed to be reversible. Unless otherwise specified, zero-order rate constants had units of , first-order rate constants had units of , and second-order rate constants had units of . The mean and standard deviation over the parameter ensemble are reported for each kinetic parameter. The value of the P2X3 and IP3R channel permeability constants have no direct literature sources and were estimated separately from data [24], [33], [56]. Leakage constants were adjusted so that the mean steady-state cytosolic calcium concentration without agonist was 0.05.