Fig. 3.

O-GlcNAc pathway mediates the K⁺ channel effects in hyperglycemia. a Schematic of O-GlcNAc modifications and targets for pharmacological interventions. b–f Inhibition of O-GlcNAc pathway using 6-diazo-5-oxo-l-norleucine (DON, 50 μmol/L) or the specific O-GlcNAc transferase (OGT) inhibitor OSMI-1 (50 μmol/L) prevented hyperglycemia-induced changes both in I_K1 density (b, c), I_to density (d), and I_to recovery kinetics (e, f) in mouse ventricular myocytes. Conversely, inhibiting the O-GlcNAc removal enzyme (O-Glc-NAcase, OGA) using Thiamet-G (Thm-G, 100 nmol/L) promoted glucose effects on K⁺ currents already in normoglycemia. Student’s paired t test; *p < 0.05, **p < 0.01, ***p < 0.001