肌浆网Ca(2+)ATP酶（SERCA）1a在心脏肌浆网中可在结构上替代SERCA2a，并增加心脏对Ca(2+)的处理能力。
Sarcoplasmic reticulum Ca(2+) atpase (SERCA) 1a structurally substitutes for SERCA2a in the cardiac sarcoplasmic reticulum and increases cardiac Ca(2+) handling capacity.
作者信息
Lalli M J, Yong J, Prasad V, Hashimoto K, Plank D, Babu G J, Kirkpatrick D, Walsh R A, Sussman M, Yatani A, Marbán E, Periasamy M
机构信息
Division of Cardiology, University of Cincinnati College of Medicine, Cincinnati, Ohio, USA.
出版信息
Circ Res. 2001 Jul 20;89(2):160-7. doi: 10.1161/hh1401.093584.
Ectopic expression of the sarcoplasmic reticulum (SR) Ca(2+) ATPase (SERCA) 1a pump in the mouse heart results in a 2.5-fold increase in total SERCA pump level. SERCA1a hearts show increased rates of contraction/relaxation and enhanced Ca(2+) transients; however, the cellular mechanisms underlying altered Ca(2+) handling in SERCA1a transgenic (TG) hearts are unknown. In this study, using confocal microscopy, we demonstrate that SERCA1a protein traffics to the cardiac SR and structurally substitutes for the endogenous SERCA2a isoform. SR Ca(2+) load measurements revealed that TG myocytes have significantly enhanced SR Ca(2+) load. Confocal line-scan images of field-stimulated SR Ca(2+) release showed an increased rate of Ca(2+) removal in TG myocytes. On the other hand, ryanodine receptor binding activity was decreased by approximately 30%. However, TG myocytes had a greater rate of spontaneous ryanodine receptor opening as measured by spark frequency. Whole-cell L-type Ca(2+) current density was reduced by approximately 50%, whereas the time course of inactivation was unchanged in TG myocytes. These studies provide important evidence that SERCA1a can substitute both structurally and functionally for SERCA2a in the heart and that SERCA1a overexpression can be used to enhance SR Ca(2+) transport and cardiac contractility.
肌浆网（SR）Ca²⁺ATP酶（SERCA）1a泵在小鼠心脏中的异位表达导致SERCA泵总水平增加2.5倍。SERCA1a心脏表现出收缩/舒张速率增加以及Ca²⁺瞬变增强；然而，SERCA1a转基因（TG）心脏中Ca²⁺处理改变的细胞机制尚不清楚。在本研究中，我们使用共聚焦显微镜证明SERCA1a蛋白转运至心脏SR并在结构上替代内源性SERCA2a同工型。SR Ca²⁺负载测量显示TG心肌细胞的SR Ca²⁺负载显著增强。场刺激SR Ca²⁺释放的共聚焦线扫描图像显示TG心肌细胞中Ca²⁺清除速率增加。另一方面，兰尼碱受体结合活性降低约30%。然而，通过火花频率测量，TG心肌细胞中兰尼碱受体的自发开放速率更高。全细胞L型Ca²⁺电流密度降低约50%，而TG心肌细胞中失活的时间进程未改变。这些研究提供了重要证据，表明SERCA1a在心脏中可在结构和功能上替代SERCA2a，且SERCA1a过表达可用于增强SR Ca²⁺转运和心脏收缩力。
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