肌浆网钙泄漏在心脏功能不全中的作用

Sarcoplasmic reticulum calcium leak and its role in cardiac dysfunction

同步肌浆网Ca^(2+)释放以外的Ca^(2+)释放即肌浆网Ca^(2+)泄漏(Ca^(2+)leak),包括Ca^(2+)火花(Ca^(2+)spark)、自发性Ca^(2+)波(spontaneous Ca^(2+)wave)和其他微小Ca^(2+)释放等。心肌细胞肌浆网Ca^(2+)泄露主要是由II型兰尼碱受体(ryanodine receptor 2,RyR2)介导的,它可以通过减少肌浆网Ca^(2+)的有效释放导致心脏收缩功能障碍;通过升高舒张期胞浆Ca^(2+)引发心脏舒张功能不全,诱发心律失常。此外,肌浆网Ca^(2+)泄露还可以引起因肌浆网Ca^(2+)回摄增多消耗更多的ATP,导致心律失常、心力衰竭等心脏疾病的进一步恶化。

Sarcoplasmic reticulum （SR） Ca^2＋ leak is defined as SR Ca^2＋ release other than that during the active excitation-contraction coupling process, which includes Ca^2＋ sparks and waves as well as smaller Ca^2＋ events. SR Ca^2＋ leak can reduce SR Ca^2＋ available for release, causing systolic dysfunction and elevate diastolic [Ca^2＋]i, contributing to diastolic dysfunction and arrhythmias. Moreover, SR Ca^2＋ leak is energetically costly because of the extra ATP used to re-pump Ca^2＋, leading to further deterioration of RyR2-related heart diseases such as arrhythmias and heart failure.