Figure 9.

Carbamazepine (Carb) and sulphonylureas share the same binding site on SUR1.A, top, representative immunoblots for SUR1 in INS-1 cells expressing WT (HA-SUR1/Kir6.2) or mutant (HA-SUR1/Kir6.2-A28V) K_ATP channels, upon treatment with DMSO, 10 μM Glib, or 10 μM Carb +10 μM Glib for 16 h. Bottom, quantification of the upper (mature) and lower bands of SUR1 is shown in the left and right plots, respectively. Data are presented as the mean ± SEM; n = 5 per group; ∗p < 0.05, ∗∗p < 0.01, ∗∗∗∗p < 0.001, compared with DMSO-treated cells in each corresponding group; differences were evaluated using two-way ANOVA and Dunnett's post hoc test. B, summary of Carb rescue of mutant K_ATP channel trafficking via two pathways. First, Carb decreases the interaction of mutant K_ATP channels with the Golgi matrix protein, GM130, allowing the mutant channels to reach the cell surface. Second, Carb attenuates autophagy-dependent protein degradation (indicated by accumulation of p62), which allows mutant K_ATP channels to pass through the ER. DMSO, dimethyl sulfoxide; ER, endoplasmic reticulum; HA, hemagglutinin; K_ATP, ATP-sensitive potassium channel; SUR1, sulfonylurea receptor 1.