Phospholamban ablation rescues the enhanced propensity to arrhythmias of mice with CaMKII-constitutive phosphorylation of RyR2 at site S2814
- Mazzocchi, Gabriela
- Sommese, Leandro Matías
- Palomeque, Julieta
- Felice, Juan Ignacio
- Di Carlo, Mariano Nahuel
- Fainstein, Diego Germán
- Gonzalez, P.
- Contreras, P.
- Skapura, D.
- Mccauley, M. D.
- Lascano, E. C.
- Negroni, Jorge Antonio
- Kranias, E. G.
- Wehrens, X. H. T.
- Valverde, Carlos Alfredo
- Mattiazzi, Ramona Alicia
DOIAbstract
Mice with constitutive pseudo-phosphorylation at Ser2814-RyR2 (S2814D+/+) have increased propensity to arrhythmias under β-adrenergic stress conditions. Although abnormal Ca2+ release from the sarcoplasmic reticulum (SR) has been linked to arrhythmogenesis, the role played by SR Ca2+ uptake remains controversial. We tested the hypothesis that an increase in SR Ca2+ uptake is able to rescue the increased arrhythmia propensity of S2814D+/+ mice. We generated phospholamban (PLN)-deficient/S2814D+/+ knock-in mice by crossing two colonies, S2814D+/+ and PLNKO mice (SD+/+/KO). SD+/+/KO myocytes exhibited both increased SR Ca2+ uptake seen in PLN knock-out (PLNKO) myocytes and diminished SR Ca2+ load (relative to PLNKO), a characteristic of S2814D...
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