Cardiac contractile function is largely mediated by the regulation of Ca²⁺ cycling throughout the lifespan. The sarco(endo)plasmic reticulum Ca²⁺ ATPase (SERCA) pump is paramount to cardiac Ca²⁺ regulation, and it is well established that SERCA dysfunction pathologically contributes to cardiomyopathy and heart failure. Phospholamban (PLN) is a well-known inhibitor of the SERCA pump and its regulation of SERCA2a - the predominant cardiac SERCA isoform - contributes significantly to proper cardiac function. Glycogen synthase kinase 3 (GSK3) is a serine/threonine kinase involved in several metabolic pathways and we and others have shown that it regulates SERCA function. In this minireview, we highlight the underlying mechanisms behind GSK3's regulation of SERCA function specifically discussing changes in SERCA2a and PLN expression, and its potential protection against oxidative stress. Ultimately, these recent findings that we discuss could have clinical implications in the treatment and prevention of cardiomyopathies and heart failure.

中文翻译：

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磷酸lamban和GSK3在调节啮齿动物心脏SERCA功能中的作用。

在整个生命周期中，心脏收缩功能主要由Ca ²⁺循环的调节介导。肌浆网（内质网）Ca ²⁺ ATPase（SERCA）泵对心脏Ca ²⁺至关重要SERCA功能障碍在病理上有助于心肌病和心力衰竭。磷脂酰肌醇（PLN）是SERCA泵的众所周知的抑制剂，其对SERCA2a（主要的心脏SERCA亚型）的调节显着促进了正常的心脏功能。糖原合酶激酶3（GSK3）是一种参与多种代谢途径的丝氨酸/苏氨酸激酶，我们和其他人已表明其调节SERCA功能。在此小型审查中，我们重点介绍GSK3调控SERCA功能的潜在机制，特别讨论SERCA2a和PLN表达的变化及其对氧化应激的潜在保护作用。最终，我们讨论的这些最新发现可能在治疗和预防心肌病和心力衰竭中具有临床意义。