Fig. 10

D2R- and GIRK-mediated currents in AST-derived dopamine neurons with α-synuclein triplication and NAS-derived dopamine neurons with normal α-synuclein levels. a Representative traces of single-neuron recordings after a brief (100 ms duration, 10 psi pressure, 50–100 μm application distance) focal application of quinpirole (5 μM) onto a NAS- (top panel) or an AST (middle panel)-derived dopamine neuron. The membrane voltage was held at − 60 mV in the voltage-clamp configuration. Superimposed representative traces (lower panel) show activation of D2R in an AST-derived dopamine neuron produced a distinctly smaller inward current, compared with the inward current measured in a NAS-derived dopamine neuron. b Representative traces of single-neuron recordings after a brief (100 ms duration, 10 psi pressure, 50–100 μm application distance) focal application of ML297 (5 μM) onto a NAS- (top) and an AST (middle)-derived dopamine neuron. Superimposed representative traces (bottom) show GIRK-mediated current in an AST-derived dopamine neuron was evidently smaller than that from a NAS-derived DA neuron. c The time course of quinpirole-induced inward currents was obtained by averaging 1 s interval activities at baseline and after quinpirole application. The inward currents in NAS-derived dopamine neurons were larger than in AST-derived dopamine neurons (†p < 0.05, Kolmogorov–Smirnov test). d The time course of ML297-induced GIRK-mediated currents was obtained by averaging 1 s interval activities at baseline and after ML297 application. The inward currents in NAS-derived dopamine neurons were larger than AST-derived dopamine neurons (†p < 0.05, Kolmogorov–Smirnov test). Inset A and B: A DIC image of a recording and a focal application pipettes during a patch-clamp experiment (scale bar, 50 μm). The analyses were performed via a blinded experimental design