RyR2 Oxidation and SR Calcium Leak Mediated Arrhythmia in DM Mice
(A) Representative Western blots of total ryanodine receptor 2 (RyR2), oxidized (DNP), and phosphorylated RyR2 (s2814 and s2808). RyR2 oxidation was increased in DM and reversed by 2-weeks of IL-1RA (3.0 mg/kg) or MT (1.0 mg/kg) treatment. RyR2 phosphorylation was not changed in DM. (B) Statistical analysis of oxidized RyR2 normalized by total RyR2. (C) Representative whole-cell patch-clamp recordings showing immediate in vitro treatment with S107 (1.0 μM for 2 h) suppressed EADs. The arrow indicates EAD. (D) One-week of S107 (30 mg/kg, subcutaneous) treatment reduced VT inducibility. Values are mean ± SEM. (B to D) The n value is indicated within the bars. ∗p < 0.05. DNP = 2,4-dinitrophenylhydrazone; O.D. = optical density; other abbreviations as in Figures 1 and 2.