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. 2021 Apr 30;129(1):98–113. doi: 10.1161/CIRCRESAHA.120.318402

Figure 4.

Figure 4.

Glucose-induced delayed afterdepolarizations are CaMKIIδ (Ca2+/calmodulin-dependent protein kinase II)-S280 O-GlcNAcylation dependent. A and B, Delayed afterdepolarizations (DADs) and spontaneous action potentials (sAPs) were increased by high-glucose treatment in control (n=21 cells from 13 animals), the increases were prevented in CaMKIIδ-S280A (n=23 cells from 12 animals). Nested t test. C and D, Glucose-induced spontaneous diastolic activities were prevented by EGTA, OSMI-1 (αR-[[(1,2-dihydro-2-oxo-6-quinolinyl)sulfonyl]amino]-N-(2-furanylmethyl)-2-methoxy-N-(2-thienylmethyl)-benzeneacetamide), and in CaMKIIδ cardiac-specific knockout (cKO) and S280A. Additional Ang II (angiotensin II) treatment further enhanced the arrhythmogenic activities, which were prevented in NOX2−/− (NADPH oxidase 2) and CaMKIIδ-cKO and mutated Met281Val and Met282Val (MMVV; n=total number of cells/animals is reported in the figure). Nested 1-way ANOVA, followed by Dunnett multiple comparisons test was used to compare 3 groups. Nested t test was used to compare 2 groups (EGTA, OSMI, Thm-G). WT indicates wild type.