Modeling changes in P2X3 receptor activity after MβCD. A, Scheme of the cyclic model of P2X3 operation with reversible multi step process adapted from . A, agonist (suffix values indicate the number of bound molecules); R, resting state; A3Ro, fully-occupied open state; A3Df, rapidly desensitizing state; ARn and ADn, bound non activated and desensitized states, respectively, with corresponding number of bound agonist molecules. Forward rate constants for activation are indicated as k, while reverse rate constants are indicated by l. The process of desensitization is indicated by n or m constants depending on the reaction direction. Intermediate transitions from each one of the upper and lower branch states are possible with rate constants indicated as r or d. For the purpose of simulating the actual experimental conditions observed with rapid, short pulse of agonist application at high concentration, the scheme is envisaged to primarily follow the R, A3Ro, A3Df, D pathway. Rate constant values are provided in Table 1 after adapting data from rat dorsal root ganglion neurons . B, Simulated responses evoked by paired pulses of α,β-meATP (10 μM, 2 s; 30 s interval) in control condition. The amplitude of the second response recovers to 24% of the first one, in analogy with experimental data. C, Similar protocol simulated after MβCD treatment. Note that the current amplitude is diminished, and the current decay is faster, while recovery from desensitization is impaired. The vertical calibration bar refers to the fraction of active receptors.