Fig. 3. Disrupting R443 electrostatic interactions inhibits DA efflux independent of DAT N-terminus phosphorylation.
a Left: representative immunoblots of surface hDAT (top), total hDAT (middle), and actin (bottom). Right: hDAT expression is quantified as a ratio of surface to total glycosylated hDAT normalized to hDAT S/D. hDAT S/D R443A had comparable expression to hDAT S/D (p > 0.05; n = 4 in triplicate). Dashed lines indicate separate sets of experiments. b Top: average 3[H]DA uptake kinetics measured in hDAT S/D R443A (gray line open squares) and hDAT S/D (green line closed triangle) cells (n = 4, in triplicate). Curves were fit to Michaelis–Menten equation to derive Km and Vmax. Bottom: the Vmax and Km for hDAT S/D R443A were comparable to hDAT S/D cells (p > 0.05). c Left: representative traces of DA efflux recorded from hDAT S/D (green trace) and hDAT S/D R443A cells (gray trace) in response to AMPH application (10 μM, indicated by arrow). Right: quantitation of peak current amplitudes (n = 9–10). DA efflux from hDAT S/D R443A (0.15 ± 0.02 pA; p = 0.01) was significantly lower compared with hDAT S/D cells (0.42 ± 0.07 pA; p = 0.0004). Data are presented as mean ± SEM. Student’s t test: a–c; two-way RM ANOVA with Bonferroni’s multiple comparison test: b.