Figure 9.
Compound 21a reverses regulatory effects of FGF14 on Nav1.6-mediated currents. (A) Representative traces of transient Na+ currents recorded from HEK-Nav1.6 co-expressing FGF14 treated with 0.1% DMSO (black) or 10 μM 21a (blue) in response to varying voltage stimuli ranging from −100 mV to + 60 mV (inset). Note the phenotypic appearance of Na+ currents with a slow entry of the channel into fast inactivation in the presence of FGF14 (panel A, black), a phenotype that was reversed in the presence of compound 21a. (B) Comparison of tau of fast inactivation at −10 mV between the indicated experimental groups. (C Current-voltage relationship for HEK-Nav1.6-FGF14 cells treated with 0.1% DMSO (black) or 10 μM 21a. (D) Comparison of peak current density between the indicated experimental groups. (E) Conductance-voltage relationship for HEK-Nav1.6-FGF14 cells treated with 0.1% DMSO (black) or 10 μM 21a. (F) Comparison of V1/2 of Nav1.6 channel activation between the indicated experimental groups. (G) Effects of 0.1% DMSO (black) and 10 μM 21a on the voltage-dependence of V1/2 of Nav1.6 channel steady-state inactivation. (H) Comparison of V1/2 of Nav1.6 channel steady-state inactivation between the indicated experimental groups. (I) Effects of 0.1% DMSO (black) and 10 μM 21a on LTI of Nav1.6 channels. LTI was characterized by plotting the fraction of Nav1.6 channels available as a function of depolarization cycle. See experimental section for additional information regarding electrophysiological protocols employed and the corresponding data analyses. (J) Bar graph summary of (I). Results are expressed as the mean ± SEM. A Student’s t-test was used to determine statistical significance. *, p < 0.05; **, p < 0.005; ***, p < 0.0005.