Figure 9.

An explicit alternating access model fit to the hDAT currents can recapitulate major features of experimental data. A, Alternating access model of hDAT function (rate constants are given for the rates at 0 mV) (see Materials and Methods). The kinetic parameters shown were used to fit the data for B–H as described below. In each case, the model simulation (color) is superimposed on the experimental data (gray). B, hDAT currents at −60 mV in response to a 1 s application of 10 μm AMPH under control conditions were normalized, aligned to the time of the peak, and averaged among cells (n = 49). C, Mean pooled experimental data for representative cells (n = 4) and model simulations for a 1 s application of 10 μm AMPH in the presence of 90 mm intracellular Na⁺. D, For control conditions, paired-pulse responses to 100 ms applications of 10 μm AMPH at a variable interval were normalized, aligned, and averaged among cells and compared with model simulations (n = 5). E, Mean pooled experimental data for representative cells (n = 3) and model simulations for paired-pulse responses to 100 ms applications of 10 μm AMPH in the presence of 90 mm intracellular Na⁺. F, Experimental and simulated dose–response relationship for AMPH-induced peak (squares) and steady-state currents (circles). G, Experimental and simulated dose–response relationship of AMPH-induced peak (squares) and steady-state currents (circles) as a function of extracellular Na⁺. H, Experimental and simulated voltage dependence of AMPH-induced peak (squares) and steady-state (circles) currents for the indicated internal solutions. Currents are normalized to the peak value at −60 mV.