Fig. 6.

NOX2-dependent ROS production mediates I_to reduction in hyperglycemia. a Schematic signaling via reactive oxygen species (ROS) that may be involved in the hyperglycemia effects on K⁺ channels. b–f Pretreatment of mouse ventricular myocytes with ROS scavengers, reduced glutathione (GSH, 10 mmol/L) and N-acetylcysteine (NAC, 10 mmol/L), prevented I_to downregulation (d) but not I_K1 (b, c) and I_to recovery (e, f) effects in hyperglycemia. I_to in NADPH oxidase 2 (NOX2)-knockout was also resistant to acute hyperglycemia. Oxidation-resistant CaMKIIδ-MMVV knock-in was not protected against acute hyperglycemia effects on either I_K1 or I_to. Two-way ANOVA; *p < 0.05, **p < 0.01, ***p < 0.001 vs. normoglycemia; ^†p < 0.05 vs. control