Fig. 2: A one-subunit model of AMPAR exhibits the expected qualitative behavior: a current peak followed by desensitization as ligand binding reaches a steady-state in a monotonic fashion, and a large displacement to higher concentrations of the current dose–response curve relative to steady-state binding.

a Diagram of the one-subunit model. b Deterministic time courses with increasing ligand concentrations. Plot shows receptor occupancy (normalized sum of all species with bound L-glutamate: R1co, R1cc, R1o, and R1d) and current (normalized species R1o, drawn with negative numbers) vs. time. Purple lines correspond to lower ligand (L-glutamate) concentration. c Plots show 12 single-channel current stochastic simulations with 1 mM L-glutamate (top) and the resulting average current of 500 such simulations (bottom). d Inset shows the design of the simulated pre-incubation experiment. Red: peak current vs L-glutamate concentration during pre-incubation. Blue: peak current obtained when stimulated with 10⁴ µM L-glutamate after being preincubated with the indicated L-glutamate concentrations. e The one-subunit model behavior is consistent with the channel operating in PRESS regime. Plot shows the dose–response curves for peak current (black solid), steady-state ligand binding (black dotted line), and ligand binding at different times after the addition of L-glutamate (slash-dotted lines coded using a colormap). Colored circles highlight AMPAR occupancy at the time of peak current at the indicated L-glutamate concentrations. The values used for the dose–response curves are from (b). Ligand concentrations that elicit 50% of maximum response are marked with solid straight black lines for the steady-state ligand binding and peak current dose–response curves. b, c τ_current and τ_rise correspond to the time at which peak current occurred or the time it took the current to decrease to 37% of peak current.