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. 2018 Dec 3;138(23):2682–2697. doi: 10.1161/CIRCULATIONAHA.118.034541

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© 2018 The Authors.

Circulation is published on behalf of the American Heart Association, Inc., by Wolters Kluwer Health, Inc. This is an open access article under the terms of the Creative Commons Attribution Non-Commercial-NoDerivs License, which permits use, distribution, and reproduction in any medium, provided that the original work is properly cited, the use is noncommercial, and no modifications or adaptations are made.

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Figure 6. — CaMKII-dependent phosphorylation of RyR2 and functional effects of CaMKII inhibition in KI hearts. A through C, Representative immunoblots (A) and quantitative assessment of the protein and phosphorylation levels of RyR2 at Ser2814 (B; *P<0.05 versus WT at baseline, ^#P<0.05 versus KI+ISO; n=6 hearts/genotype) and Ser2808 (C; *P<0.05 versus WT at baseline; n=5 hearts/genotype) from left ventricle sections in littermates of WT and KI perfused hearts±1 μM ISO or 1 μM KN93. D and E, Representative traces of the action potentials (D) and cumulative incidence of DADs (E; **P<0.01) after a stimulation pause after a 2-Hz field stimulation in KI cardiomyocytes±1 μM ISO or 1 μM KN93. F and G, Representative traces of SCaTs (F) and the cumulative incidence of SCaTs (G; **P<0.01) after a stimulation pause after a 2-Hz field stimulation in KI cardiomyocytes±1 μM ISO or 1 μM KN93. H, Cumulative data of Ca²⁺ spark frequency in KI cardiomyocytes±ISO (*P<0.05; **P<0.01). I, Cumulative data of caffeine-induced Ca²⁺ transient amplitude (ie, SR Ca²⁺ content) in KI cardiomyocytes±ISO (*P<0.05). J, Cumulative incidence of ventricular arrhythmias in KN93-pretreated KI mice after an intraperitoneal injection of 2 mg/kg epinephrine (*P<0.05; n=10 KI mice for each group). CaMKII indicates calcium/calmodulin-dependent kinase II; DADs, delayed afterdepolarizations; GAPDH, glyceraldehyde-phosphate dehydrogenase; ISO, isoproterenol; KI, knockin; RyR2, ryanodine receptor type 2; SCaTs, spontaneous Ca²⁺ transients; and WT, wild type.