From Ca²⁺ dysregulation to heart failure: β-adrenoceptor activation by RKIP postpones molecular damages and subsequent cardiac dysfunction in mice carrying mutant PLN^R9C by correction of aberrant Ca²⁺-handling

Impaired cardiomyocyte Ca^(2+) handling is a central hallmark of heart failure (HF), which causes contractile dysfunction and arrhythmias. However, the underlying molecular mechanisms and the precise contribution of defects in Ca^(2+)-cycling regulation in the development of HF are still not completely resolved. Here, we used transgenic mice that express a human mutation in the cardiomyocyte Ca^(2+)-regulator phospholamban (PLN^(R9C)-tg) causing severe HF due to a reduction in Ca^(2+) …