Figure 5
From: Amyloid precursor protein modulates Nav1.6 sodium channel currents through a Go-coupled JNK pathway
Thr-668 phosphorylation of APP enhances sodium current expression.
(A) Normalized current-voltage relationships of currents in oocytes expressing Nav1.6 α subunits alone (a; open squares) and together with APP (a; closed circles), APP plus CDK5 inhibitor (a; Roscovitine 10 μM; open triangles) and APP plus JNK inhibitor (a; JNK inhibitor III 7 μg/ml, closed triangles). The mean peak sodium current amplitude in oocytes injected with Nav1.6 and APP and applied with the indicated inhibitors (b). (B) Normalized current-voltage relationships of currents in oocytes expressing Nav1.6 α subunits alone (a; open squares) and together with wild-type APP (a; closed circles), APP T668E (a; open triangles), and APP T668A (a; closed triangles). The mean peak sodium current amplitude in oocytes injected with Nav1.6 and the indicated APP or APP mutant cRNAs (b). (C) Normalized current-voltage relationships of currents in oocytes expressing Nav1.6 α subunits with APP T668E alone (open squares) and together with a dominant active mutant of Go protein α subunit (Q205L, closed squares) or a dominant negative mutant of the Go protein α subunit (G203T; closed triangles) (a). The mean peak sodium current amplitude in oocytes injected with Nav1.6 and T668E and the Go mutant cRNAs (b). (D) Normalized current-voltage relationships of currents in oocytes expressing Nav1.6 α subunits with APP T668A alone (open squares) and together with a dominant active mutant of Go protein α subunit (Q205L, closed squares) or a dominant negative mutant of the Go protein α subunit (G203T; closed triangles) (a). The mean peak sodium current amplitude in oocytes injected with Nav1.6 and T668A and the Go mutant cRNAs (b). Insert: Representative examples of sodium current responses elicited by depolarizing voltage steps. One-way ANOVA. **p < 0.01; Error bars represent mean ± S.E.
