Figure 2

APP enhances of sodium current expression through modulation of α-subunit of Nav1.6.

(A) Sodium current expression is reduced in hippocampal neurons from APP KO mouse. Whole cell recordings of voltage-gated sodium currents from hippocampal slice of APP KO and WT mice at 7–8 weeks old of age. Sodium current responses elicited by depolarizing voltage steps (from −60 mV to 60 mV, 10 mV increments) in a neuron from WT and APP KO mice. (a), Current-voltage relationships of sodium currents density in WT mice (open squares) and APP KO mice (solid circles). pF, picofarads. (b) Peak currents density in APP KO and their littermate WT mice. (B) Overexpression of APP enhances sodium currents in HEK293 cells stably expressing α-subunit of human Nav1.6 (HEK293-Nav1.6 cells). Whole cell recordings of voltage-gated sodium currents in APP- and empty vector (vector)-transfected HEK293-Nav1.6 cells. Sodium current responses elicited by depolarizing voltage steps (from −60 mV to 60 mV, 10 mV increments). (a), Current-voltage relationships of sodium currents density in vector-(open squares) and APP-transfected HEK293-Nav1.6 cells (closed circles). pF, picofarads. (b), Peak currents density in vector- and APP-transfected HEK293-Nav1.6 cells. (C) APP enhances sodium currents in Xenopus oocytes. Two-electrode voltage-clamp recordings in oocytes which were injected cRNA for Nav1.6 α subunits and together with APP. The oocytes injected cRNA for Nav1.6 α subunits alone were recorded as the control. Sodium current responses elicited by depolarizing voltage steps (−75 mV to 40 mV, 5 mV increments). (a), Normalized current-voltage relationships of currents in oocytes expressing Nav1.6 α subunits alone (open squares) and together with APP (closed circles). (b), Sodium peak currents in oocytes expressing Nav1.6 α subunits alone and together with APP. (D) Normalized current-voltage relationships of sodium currents by two-electrode voltage-clamp recordings in oocytes injected cRNA for Nav1.6 α subunit alone (open squares) and those injected cRNA for Nav1.6 α subunitvand the reversed sequence of APP (closed circles). (E) Normalized current-voltage relationships of sodium currents by two-electrode voltage-clamp recordings in oocytes expressing Nav1.5 α subunit alone (open squares) and those expressing Nav1.5 α subunit together with APP (closed circles). Insert: Representative examples of sodium current responses elicited by depolarizing voltage steps. One-way ANOVA, *p < 0.05; **p < 0.01; ***p < 0.001. Error bars represent mean ± S.E.