Figure 7.

Phenytoin and riluzole suppress activity of EIEE13 patient iNeurons. (A) Patch-clamp recording of a spontaneously active Patient 3 (P3) neuron before, during, and after washout of 3 µM riluzole. Riluzole inhibited all spontaneous activity but was completely reversible with washout. (B) The threshold voltage for single evoked action potentials was measured before and after riluzole exposure. For both controls and Patient 3, riluzole raised the action potential threshold to more depolarized potentials. (C and D) Changes in per cent spikes in network bursts in patient and control iNeurons in response to increasing concentrations of riluzole (C; 0, 0.3, 1, and 3 µM) and phenytoin (D; 0, 8, 24, and 80 µM). n = 8 independent experiments for C2 and P1, respectively; n = 5 independent experiments for C3 and P3, respectively. Within group comparisons for drug dosage effect compared to vehicle (DMSO) were performed using a one-way ANOVA. (E and F) Grouped control and patient data from C and D, respectively. n = 13 for each group. Data are depicted as box and whisker plots of mean, maximum, minimum, and upper and lower quartiles. Two-way unpaired ANOVA (due to missing values) was performed. All post hoc analyses used the two-stage linear step-up procedure post-test. *P < 0.05, **P < 0.01, ***P < 0.001, and ****P < 0.0001.