Is the enhancement of the sarcoplasmic reticulum function susceptible to arrhythmias?

钙不仅是正常肌肉收缩和舒张所必需的，而且是心脏各种信号通路的重要第二信使。越来越多的证据表明，Ca^<2+>稳态和Ca^<2+>依赖的信号通路在心脏肥厚和心力衰竭的发展中起关键作用。通过心脏SR Ca^<2+> atp酶（SERCA2a）增强Ca^<2+ bb0摄取可能对心力衰竭具有潜在的治疗价值。心律失常是Ca^<2+>摄取增强的潜在不良影响。为了确定这种治疗的安全性，我们检测了显示出几乎最大SERCA2a活性的磷蛋白敲除小鼠对心律失常的易感性。程序电生理研究和遥测心电图显示，磷蛋白消融对小鼠心律失常不敏感。这些数据表明，磷蛋白消融可能是一种新的治疗心力衰竭的策略，没有心律失常的潜在风险。

Calcium is not only indispensable for normal muscle contraction and relaxation but also an important second messenger of various signaling pathways in the heart. A growing body of evidence has shown that Ca^<2+> homeostasis and Ca^<2+> -dependent signaling pathways play a pivotal role in the development of cardiac hyperirophy and heart failure. The enhancement of Ca^<2+> uptake via cardiac SR Ca^<2+> ATPase (SERCA2a) may have potential therapeutic value for heart failure. Arrhythmogenesis is a potential adverse effect of the enhancement of Ca^<2+> uptake. To establish the safety of this treatment, we examined the susceptibility of arrhythmias in phospholamban knockout mice which display the almost maximal SERCA2a activity. The programmed electrophysiological study and telemetry electrocardiography revealed that phospholamban ablation was not susceptible to arrhythmias in mice. The data indicated that phospholamban ablation could be a novel therapeutic strategy for heart failure without the potent risk of arrhythmogenesis.