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

摘要: 同步肌浆网Ca2+释放以外的Ca2+释放即肌浆网Ca2+泄漏（Ca2+ leak），包括Ca2+火花（Ca2+ spark）、自发性Ca2+波（spontaneous Ca2+ wave）和其他微小Ca2+释放等。心肌细胞肌浆网Ca2+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Ca2+的有效释放导致心脏收缩功能障碍；通过升高舒张期胞浆Ca2+引发心脏舒张功能不全，诱发心律失常。此外，肌浆网Ca2+泄露还可以引起因肌浆网Ca2+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。

Abstract: Sarcoplasmic reticulum (SR) Ca2+ leak is defined as SR Ca2+ release other than that during the active excitation-contraction coupling process, which includes Ca2+ sparks and waves as well as smaller Ca2+ events. SR Ca2+ leak can reduce SR Ca2+ available for release, causing systolic dysfunction and elevate diastolic ［Ca2+］i, contributing to diastolic dysfunction and arrhythmias. Moreover, SR Ca2+ leak is energetically costly because of the extra ATP used to re-pump Ca2+, leading to further deterioration of RyR2-related heart diseases such as arrhythmias and heart failure.