Figure 3. Enhanced Persistent Na⁺ Current Underlies AP Threshold Changes in Fmr1 KO neurons.

(A) I_NaP evoked by a depolarizing voltage ramp (−100 to −20 mV, 20 mV/s) before (traces a) and during (traces b) application of TTX. TTX-sensitive current (traces c) was obtained by subtraction. Note that the large escaped AP currents were truncated to emphasize the I_NaP.

(B) I-V curves (B₁) were constructed from the ramp evoked I_NaP (mean current value over 0.01 mV intervals from averages of 4–5 trials for each cell to approximating quasi-steady state current). Currents were normalized to corresponding cell capacitance for better comparison. (B₂) I_NaP at −40 mV was significantly large in Fmr1 KO neurons.

(C) Voltage-dependent activation curve of I_NaP (C₁). Data fitted by Boltzmann function. Summarized data of half activation voltage V_1/2 (C₂).

(D) I_NaP evoked by a repolarizing ramp (D₁, +30 to −65 mV, −50 mV/s). For better comparison with (A), the traces are presented in the same direction as in (A) in a −65 to −20 mV range. Arrow indicates the time direction. (D₂) The difference of I-V curves between WT and Fmr1 KO neurons. Insert: I_NaP at −40 mV. (D₃) The voltage-dependent activation of I_NaP in Fmr1 KO and WT neurons. Insert: V_1/2 of I_NaP activation.

(E) Effects of I_NaP inhibitor riluzole on the I_NaP and AP threshold in Fmr1 KO and WT neurons. (E₁) Sample I_NaP traces. (E₂) I-V curves. Insert, I_NaP at −40 mV. (E₃) Effects of I_NaP inhibitor riluzole and I_NaP opener veratridine on AP threshold.

* p < 0.05; ** p < 0.01; ns, not significant. All data are mean ± SEM.