Ablation of phospholamban rescues reperfusion arrhythmias but exacerbates myocardium infarction in hearts with Ca2+ /calmodulin kinase II constitutive phosphorylation of ryanodine receptors
- Valverde, Carlos Alfredo
- Mazzocchi, Gabriela
- Di Carlo, Mariano Nahuel
- Ciocci Pardo, Alejandro
- Salas, Nehuen
- Ragone, María Inés
- Felice, Juan Ignacio
- Consolini, Alicia Elvira
- Portiansky, Enrique Leo
- Mosca, Susana Maria
- Kranias, Evangelia G.
- Wehrens, Xander H. T.
- Mattiazzi, Ramona Alicia
DOIAbstract
Aims Abnormal Ca2+ release from the sarcoplasmic reticulum (SR), associated with Ca2+ -calmodulin kinase II (CaMKII)-dependent phosphorylation of RyR2 at Ser2814, has consistently been linked to arrhythmogenesis and ischaemia/reperfusion (I/R)-induced cell death. In contrast, the role played by SR Ca2+ uptake under these stress conditions remains controversial. We tested the hypothesis that an increase in SR Ca2+ uptake is able to attenuate reperfusion arrhythmias and cardiac injury elicited by increased RyR2-Ser2814 phosphorylation. Methods and results We used WT mice, which have been previously shown to exhibit a transient increase in RyR2-Ser2814 phosphorylation at the onset of reperfusion; mice with constitutive pseudo-phosphorylation o...
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