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

Figure 6.

Figure 6.

Diabetes-induced diastolic sarcoplasmic reticulum (SR) Ca2+ leak is CaMKIIδ (Ca2+/calmodulin-dependent protein kinase II)-S280 O-GlcNAcylation-dependent. A, Experimental protocol and representative intracellular Ca2+ signals (as changes in Fluo-4 fluorescence) showing spontaneous Ca2+ waves in wild type (WT) following 4-week of streptozotocin (STZ)-induced diabetes. B, Diabetes slightly reduced the amplitude of the intracellular Ca2+ transient and prolonged the Ca2+ transient decay without significantly altering SR Ca2+ load (n[CaT]=total number of cells/animals, WT+vehicle/normal glucose=16/7, WT+vehicle/high-glucose=9/7, WT+STZ/normal glucose=20/6, WT+STZ/high-glucose=11/6, S280A+STZ/normal glucose=13/5, S280A+STZ/high-glucose=11/5, mutated Met281Val and Met282Val [MMVV]+STZ/normal glucose=13/5, MMVV+STZ/high-glucose=10/5; n[SR load]=total number of cells/animals, WT+Vehicle=12/6, WT+STZ=12/7, S280A+STZ=9/5, MMVV+STZ=10/5). Acute effect of high-glucose within the same genotype/treatment was tested using nested t test. Effect of STZ-induced diabetes (in normal glucose) vs WT+Vehicle was tested using nested 1-way ANOVA, followed by Dunnett multiple comparisons test. C, Ca2+ sparks were increased in diabetic WT and further increased by acute high-glucose treatment. D, The increase in Ca2+ spark rate was prevented in CaMKIIδ-S280A and was attenuated in the CaMKIIδ-MMVV (n=total number of cells/animals, WT+Vehicle=12/6, WT+STZ=10/6, S280A+STZ=9/5, MMVV+STZ=10/5). Nested t test. CaSpF indicates Ca2+ spark frequency.