Fig. 4. The effect of ERG channel activator on tonic discharges of subthalamic neurons.

(A to C) Three representative subthalamic neurons that fire in spontaneous tonic activity at a “resting” membrane potential of about −60 mV are shown. The horizontal dashed lines indicate the level of −60 mV. Continuous recording of spontaneous activity in a representative neuron from a rat is provided in fig. S8. (A) PD-118057 (0.5 μM) reversibly hyperpolarizes the membrane (marked by arrows) and turns the tonic spikes into burst discharges (see also Fig. 6A and fig. S4B). (B) The firing mode switching as well as the hyperpolarizing effects of 0.5 μM PD-118057 are abolished by the coapplication of the ERG channel inhibitor E-4031 (5 μM). (C) The tendency toward bursts is correlated with the concentration of PD-118057 as well as its effect on membrane hyperpolarization (marked by arrows). (D to I) There are prominent effects of PD-118057 (0.5 μM) on the burst rate (D), intraburst spike frequency (E), spikes per burst (F), the lowest membrane potential (G), AHP amplitude (H), and the frequency of hyperpolarizing overshoot (I; the hyperpolarization period more negative than the resting membrane potential) (each n = 4). (J) The effects of E-4031 [5 μM; data from Fig. 3 (n = 8)], dofetilide [5 μM; data from Fig. 3 (n = 4)], and PD-118057 (0.5 μM; n = 4) on the interspike intervals and the coefficient of variance of the interspike intervals are compared. *P < 0.05; **P < 0.01 compared to control, paired two-tailed Student’s t test. N.A., not applicable (no bursts for analysis in that condition). Scale bars, 20 mV/2 s. Animals used: p18 to p26 mice.