Figure 6.

Radial plots summarizing the mechanism of action of ZL181 in heterologous cells and in MSNs. (a) Peak current density (top), V_1/2 of activation (right, defined as “voltage-sensitivity”), tau of fast inactivation (bottom) and available fraction of channels calculated from V1/2 of steady-state inactivation (left) in HEK-Nav1.6 cells treated with ZL181 and expressing either full-length FGF14-GFP (red) or FGF14-ΔNT-GFP (green); data sets are normalized to respective controls treated with DMSO (either full-length FGF14-GFP or FGF14-ΔNT-GFP; these two control data sets are displayed in blue in Figures 3 and 4, respectively). The data points inside the gray box represent suppression (green line) or increase (red line) of Nav1.6 channel function in the presence of ZL181 compared to respective DMSO control. (b) Mean firing frequency (top), action potential voltage threshold (right), instantaneous firing frequency (bottom), and action potential current threshold (left) in Fgf14^+/+ wild type MSNs exposed to ZL181 (yellow line) compared to DMSO controls (dotted line); data are normalized to their respective controls treated with DMSO (displayed in black in Figure 5a–h). The action potential current threshold value is absolute as it refers to absolute V_m values (i.e., a V_thr of –40 mV is referred to as “40 mV”). The data points inside the gray box represent suppression (yellow line) of intrinsic firing in the presence of ZL181 compared to respective DMSO control.