Molecular Mechanism for Calcium Signaling in Cardiomyocyte

肌肉的收缩能力受细胞内钙的调节。当质膜去极化时，钙通过钙释放通道从肌浆网释放到细胞质内，导致肌肉收缩。另一方面，肌浆网钙ATPase对钙的摄取降低了钙浓度，从而导致肌肉松弛。与钙调素结合的钙离子储存在肌浆网中。Ca-ATPase活性受磷蛋白的调节。肌浆网在兴奋-收缩偶联中起着重要作用。心肌肥厚和心力衰竭时钙信号蛋白表达水平的变化可能影响心功能。在本研究中，我们分析了钙释放通道和磷蛋白基因表达的机制。我们确定了基因中的启动子区域和可能的转录因子来表达。我们对Ca-ATPase和Phopholamban的结构-功能分析表明，Phopholamban的一个功能单元是单体，而低聚物则是分子的池。我们发现连接蛋白43的胞外二硫键是形成缝隙连接的关键，心肌细胞之间通过缝隙连接进行交流。

Muscle contractility is regulated by Intracellualr calcium. Upon depolarization of plasma membrane, Ca is released into cytoplasm from the sarcoplasmic reticulum through Ca release channel, leading to muscle contraction. On the other hand, Ca uptake by Ca ATPase in sarcoplasmic reticulum lowers Ca concentration to induce muscle relaxation. Ca, which binds to calsequestrin, is stored in the sarcoplasmic reticulum. The activity of Ca ATPase is regulated by phospholamban. The sarcoplasmic reticulum plays an important role in exitation-contraction coupling. The changes in expression levels of the Ca signaling proteins in cardiac hypertrophy and heart failure may influence on a cardiac performance. In this study, we analyzed the mechanism for gene expression of Ca release channel and phospholamban. We identified the promotor regions in the genes and possible transcriptional factors for expression. Our structure- function analysis of Ca ATPase and phopholamban revealed that a functional unit of phopholamban is a monomer and an oligomer serves as a pool of the molecule. We showed that extracellular disuffide bonds of connexin 43 are crucial for formation of gap junction, through which cardiomyocytes communicate each other.