FIGURE 6.

The N-terminal domain of FGF14 is required for peptides to exert modulatory effects on Nav1.6 channel inactivation. (A) Conductance-voltage relationships for HEK293-Nav1.6 cells co-expressing FGF14-ΔNT-GFP treated with 0.1% DMSO, 50 µM PLEV and 50 µM EYYV. (B) Comparison of V1/2 of activation between the indicated experimental groups. (C) Normalized current as a function of membrane potential to characterize the effects of 0.1% DMSO, 50 µM PLEV and 50 µM EYYV on steady-state inactivation. (D) Comparison of V1/2 of steady-state inactivation between the indicated experimental groups. (E) Ratio maximal INa plotted as a function of depolarization cycle to characterize entry of Nav1.6 channels exposed to 0.1% DMSO, 50 µM PLEV, or 50 µM EYYV in the presence of FGF14-ΔNT. Cells were subjected to four 0 mV 16 ms depolarizations separated by −90 mV 40 ms recovery intervals. (F) Bar graph represented 2nd, 3rd, and 4th pulse of LTI. (G,H) Assessment of cumulative inactivation of Nav1.6 channels exposed to 0.1% DMSO, 50 µM PLEV, or 50 µM EYYV in the presence of FGF14-ΔNT. It was examined by applying a 2 ms test pulse to −10 mV 20 times at frequency10 Hz from a holding potential of −80 mV. Data are mean ± SEM. Significance was assessed using an Student’s t-test comparing cells treated with 0.1% DMSO, 50 µM PLEV and 50 µM EYYV. NS = non-significant; *, p at least < 0.05 (detailed p values and summary of results are reported in Tables 2, 4).