Figure 5. The Y777H Variant Causes Cell-Type-Specific Increases in K_Na Currents.

(A₁–C₁) Representative traces in control external solution (top), 0.5 mM TTX (middle), and the difference current (bottom), which was calculated by subtracting the membrane current response to voltage steps (−80 to +50 mV) in TTX from the response in control, in WT (black) and Kcnt1^m/m (colors) neurons.

(A₂–C₂) Summary data show the K_Na current (mean ± SEM) for each voltage step in WT (black and gray) and Kcnt1^m/m (colors) neurons.

(A₃–C₃) Plots of the K_Na current (mean ± SEM) for each voltage step from −80 to 0 mV in WT (black and gray) and Kcnt1^m/m (colors) neurons to illustrate the values that are too small to be seen on the graphs in A₂-C₂.

(A₄–C₄) Normalized Conductance-Voltage (G-V)plots (mean ± SEM) for WT (black and gray) and Kcnt1^m/m (colors) neurons with Boltzmann fits. Insets show the V_m at half-maximum (V₅₀; mean ± SEM).

(A₅–C₅) Plots of the total membrane current (mean and SEM) for each voltage step from −60 to +50 mV in WT (black) and Kcnt1^m/m (colors) neurons. Insets show values too small to be seen on the larger graph. Shaded red areas indicate significantly higher currents in Kcnt1^m/m neurons. The plots below show the fractional increase in the total membrane current (ΔI/I, mean ± SEM) caused by the Y777H variant. Statistical significance for Current-Voltage (I-V) plots was tested using generalized linear mixed models with genotype and current step as fixed effects followed by pairwise comparisons at each level.

p values < 0.05 are labeled on the plots in A₂–C₂ as asterisks and on the plots in A₃–C₃ as red numbers. p values < 0.001 are labeled on the plots in A₄–C₄ as three asterisks. See also Figures S4 and S5.