Ablation of sarcolipin enhances sarcoplasmic reticulum calcium transport and atrial contractility
Ablation of sarcolipin enhances sarcoplasmic reticulum calcium transport and atrial contractility
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DOI：
10.1073/pnas.0707722104
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发表时间：
2007-11-06
影响因子：
11.1
通讯作者：
Periasamy, Muthu
中科院分区：
文献类型：
--
作者：
Babu, Gopal J.;Bhupathy, Poornima;Periasamy, Muthu
Sarcolipin是一种新的心肌肌浆网钙ATPase 2a(SERCA2a)调节剂，在心房中大量表达。在这项研究中，我们通过建立一种肌磷脂缺乏的小鼠模型来研究肌磷脂在心脏中的生理学意义。肌磷脂缺失的小鼠没有表现出任何发育异常或任何心脏病理。肌磷脂的缺失并不改变其他钙离子调节蛋白的表达水平，特别是磷蛋白的表达水平及其磷酸化状态。钙摄取研究表明，在心房，肌磷脂的消融导致SERCA泵对钙的亲和力增加和钙摄取速率的最大速度增加。一个重要的发现是，肌磷脂的消融导致心房钙瞬变幅度增加，这导致心房收缩能力增强。此外，肌磷脂缺失小鼠的心房对异丙肾上腺素刺激表现出迟钝的反应，暗示肌磷脂是心房中A肾上腺素能反应的媒介。我们的研究证明，肌磷脂是心房中SEIRCA2a的关键调节因子。重要的是，我们的数据表明，在心房和心室中存在不同的SERCA泵调节器。
Sarcolipin is a novel regulator of cardiac sarcoplasmic reticulum Ca2+ ATPase 2a (SERCA2a) and is expressed abundantly in atria. In this study we investigated the physiological significance of sarcolipin in the heart by generating a mouse model deficient for sarcolipin. The sarcolipin-null mice do not show any developmental abnormalities or any cardiac pathology. The absence of sarcolipin does not modify the expression level of other Ca2+ handling proteins, in particular phospholamban, and its phosphorylation status. Calcium uptake studies revealed that, in the atria, ablation of sarcolipin resulted in an increase in the affinity of the SERCA pump for Ca2+ and the maximum velocity of Ca2+ uptake rates. An important finding is that ablation of sarcolipin resulted in an increase in atrial Ca2+ transient amplitudes, and this resulted in enhanced atrial contractility. Furthermore, atria from sarcolipinnull mice showed a blunted response to isoproterenol stimulation, implicating sarcolipin as a mediator of A-adrenergic responses in atria. Our study documented that sarcolipin is a key regulator of SEIRCA2a in atria. Importantly, our data demonstrate the existence of distinct modulators for the SERCA pump in the atria and ventricles.