Kusakari Yoichiro, Hirano Shuta, Hongo Kenichi, Nakayama Hiroyuki, Otsu Kinya, Kurihara Satoshi
Department of Physiology (II), The Jikei University School of Medicine, Tokyo, Japan.
Nihon Yakurigaku Zasshi. 2004 Feb;123(2):87-93. doi: 10.1254/fpj.123.87.
Cytosolic Ca(2+) is a key regulator of excitation-contraction coupling in myocardium. Myocardial contractile dysfunction in heart failure is characterized by a decrease in contraction and prolonged relaxation. These alterations are mainly due to changes in 1) intracellular Ca(2+) transients (CaT), 2) Ca(2+) sensitivity of the contractile elements, and/or 3) contractile proteins. It is useful to investigate the relationship between CaT and contraction for understanding of the mechanism of contractile dysfunction in heart failure. There are many reports regarding the alterations in CaT, Ca(2+) sensitivity, and contractile proteins in heart failure. Changes in the activity of the sarcoplasmic Ca(2+) pump protein, SERCA2a, may be involved in the altered contractility in heart failure. We generated cardiac-restricted overexpression of SERCA2a transgenic mice (TG) and non-transgenic littermates (NTG). To investigate the role of SERCA2a activity for ischemic heart, we used acidosis as a model of acute contractile dysfunction. During acidosis and recovery from acidosis, the peaks of CaT and tension in TG were significantly larger than those in NTG. These results suggest that an increase in the activity of SERCA2a could be beneficial to preserve contractility during acidosis and recovery. Thus, a disturbance of the intracellular Ca(2+) homeostasis is one of the key factors for the contractile dysfunction in heart failure.
胞质钙离子（Ca(2+)）是心肌兴奋 - 收缩偶联的关键调节因子。心力衰竭时心肌收缩功能障碍的特征是收缩减弱和舒张延长。这些改变主要归因于以下方面的变化：1）细胞内钙离子瞬变（CaT），2）收缩元件对钙离子的敏感性，和/或3）收缩蛋白。研究CaT与收缩之间的关系有助于理解心力衰竭时收缩功能障碍的机制。关于心力衰竭时CaT、钙离子敏感性和收缩蛋白的改变已有许多报道。肌浆网钙离子泵蛋白SERCA2a活性的变化可能与心力衰竭时收缩力的改变有关。我们构建了心脏特异性过表达SERCA2a的转基因小鼠（TG）和非转基因同窝小鼠（NTG）。为了研究SERCA2a活性对缺血心脏的作用，我们将酸中毒作为急性收缩功能障碍的模型。在酸中毒期间及从酸中毒恢复过程中，TG组的CaT峰值和张力峰值显著大于NTG组。这些结果表明，SERCA2a活性的增加可能有助于在酸中毒及恢复过程中维持收缩力。因此，细胞内钙离子稳态的紊乱是心力衰竭时收缩功能障碍的关键因素之一。
