Figure 8.
DA SN neurons in A53T-SNCA mice display reduced A-type potassium currents and glutathione-mediated rescue of A-type currents. A, B, Voltage-clamp traces of whole-cell (swc) and nucleated outside-out (nuo, insets) recordings of DA SN neurons in control (A) and A53-SNCA mice (B), showing fast inactivating potassium channel currents in response to depolarizing voltage steps (increments swc: 5 mV; nucleated 10 mV) from a prepotential of −100 mV. Scale bars: swc, 200 ms, 500 pA; nuo, 200 ms, 300 pA. C, Mean steady-state activation of A-type (Kv4.3) potassium conductances (mean ± SEM) recorded in standard whole-cell in DA SN neurons of wild-type and A53T-SNCA mice. Lines in C and E represent fits of the mean data with Boltzmann equations. D, E, Voltage-clamp traces of whole-cell patch-clamp recordings showing the in vitro dialysis of 10 mm GSH on DA SN neurons in control (D) and A53T-SNCA mice (E). Scale bars, 400 pA, 200 ms. F, Graph showing the relative change of A-type potassium current (mean ± SEM) upon GSH dialysis on DA SN neurons from control (black) and A53T-SNCA (red) mice, respectively. The black and red lines represent exponential fits of mean control and A53T data, respectively. G, Mean Kv4 conductances (mean ± SEM, ns) in DA SN neurons of control and A53T-SNCA mice and the Kv4 conductance after GSH dialysis. Note the significant decrease of Kv4 conductance in the DA SN neurons of the A53T-SNCA mice compared with controls and the significant increase of Kv4 conductances in A53T-SNCA after GSH dialysis compared with those in A53T-SNCA recorded under control conditions. H, Frequency changes in the DA SN neurons of control (black) and A53T-SNCA (red) mice in response to GSH dialysis. Current-clamp traces showing the spontaneous in vitro activity of DA SN neurons in A53T-SNCA mice after 10 and 200 s dialysis of GSH (top). Graph showing the relative changes in mean frequencies of DA SN neurons in control (black) and A53T-SNCA mice (red), respectively, during GSH dialysis (bottom). Note the significant decrease of mean frequency during GSH dialysis in DA SN neurons of A53T-SNCA mice, compared with controls. The black and red lines represent exponential fits of mean control and A53T data, respectively. Mann–Whitney test; ***p < 0.0005, **p < 0.005, *p < 0.05.