Fig. 3. Whole-cell patch-clamp recording of spontaneous neuronal activity modulated by different ERG inhibitors in acute STN slices.

(A) Top: E-4031 (5 and 10 μM) decreases burst discharges and the intraburst spike frequency and even turns bursts into single spikes in a higher concentration (see also fig. S6A). Inset: Superimposed bursts in the absence (black) and the presence (red) of 5 μM E-4031 demonstrate a decreased AHP in the latter condition (see also fig. S9A). Continuous recording of spontaneous activity in a representative neuron is provided in fig. S8. Bottom: 5 μM dofetilide as well as 10 nM astemizole reduce burst discharges. Inset: Superimposed bursts in the absence (black) and presence (red) of 5 μM dofetilide once again demonstrate a decreased AHP by dofetilide. (B) The spontaneous tonic activity is not affected by E-4031, dofetilide, and astemizole. (C to G) For the burst mode, the effects of E-4031 (5 μM) on the burst rate (C), intraburst spike frequency (D), the number of spikes per burst (E), postburst AHP amplitude (F), and the lowest potential (G) are analyzed (each n = 5). (H to K) The effects of E-4031 (5 μM; H and I) or dofetilide (5 μM; J and K) on single-spike frequency and coefficient of variance of the interspike intervals (n = 4 for dofetilide and n = 8 for the others). *P < 0.05 compared to control, paired two-tailed Student’s t test. Scale bars, 20 mV/1 s. Animals used: p18 to p26 mice.