Figure 2. GSK3 inhibition suppresses I_NaP during the day but not the night.

(a,b,d,e) Average normalized response to slow depolarizing voltage ramp (−100 to +10 mV; 59 mV s⁻¹) from SCN cells treated with (a,d) vehicle (DMSO, 0.002%; black) or (b,e) GSK3 inhibitor (CHIR, 1 μM; blue) at baseline and after 3-min treatment with persistent sodium current blocker, riluzole (20 μM; grey). (c,f) Peak inward current (mean±s.e.m.) at baseline and after riluzole treatment. During the day (c) CHIR-treated cells (blue) had significantly reduced inward current at baseline (*P=0.042) that was lost after blockade of I_NaP with riluzole (P=0.350). Two-way, mixed-design ANOVA; Treatment X Riluzole interaction, F_(1,31)=5.455, P=0.026; n=13–20 cells, four animals per group. At night (f) peak inward current did not differ between CHIR- and vehicle-treated cells at baseline or after treatment with riluzole (non-significant main effect of CHIR, F_(1,33)=0.150, P=0.748; n=13–22 cells, four animals per group). Recordings made between ZT 4–8 (a–c) or ZT 14–18 (d–f).