(A) Model used for simulating agonist responses replicated from Gielen and Corringer (Gielen and Corringer, 2018) with adjustments made to the rate constants to approximate ELIC responses. R = resting, F = flipped (pre-active), O = open, D = desensitized. States with I represent inhibitor-bound states (e.g. DHA). kon = 4,400 M–1s–1, koff = 80 s–1, f+ = 50 s–1, f- = 5000 s–1,β = 10,000 s–1, α = 100 s–1, d+ = 0.7 s–1, d- = 0.01 s–1, k’on = 10,000 M–1s–1, k’off = 0.1 s–1. To reproduce the effect of DHA inhibition of ELIC responses, rate constants leaving AFI were decreased by 105-fold. (B) Simulated currents were generated by applying 30 mM agonist and pre-applying inhibitor. (C) Simulation shows the probability of occupying the inhibitor-bound pre-active state (AFI) with 30 mM agonist, and high (1 mM) and low (0.1 μM) concentrations of inhibitor. High concentrations of inhibitor drive the channel entirely into the AFI state at steady state. (D) From the simulated responses, graphs show decrease in peak response, increase in the rate of current decay, and decrease in steady state current with increasing concentration of inhibitor. The inhibitor leads to a small left-shift in the agonist dose response curve (EC50 = 2.1 mM for [I] = 1e-7 M, EC50 = 1.8 mM for [I] = 1e-5 M).