The role of sodium calcium exchanger (NCX)on cardiac function.

质膜上的Na^+-Ca^<2+>交换器（NCX）被认为是许多哺乳动物可兴奋细胞（包括心肌细胞）从细胞质溶胶到细胞外空间的主要钙挤出系统。NCX的三种哺乳动物亚型（NCX1、NCX2和NCX3）已被分离出来，NCX1在心脏中高水平表达。然而，由于缺乏特异性的NCX抑制剂，NCX在心脏中的病理生理作用尚不清楚。为了确定NCX在心脏收缩和心肌肥厚发生中的作用，我们通过收缩NCX杂合敲除（KO）小鼠的横主动脉对心脏施加压力过载，并在术后3周检测心功能和形态学。虽然假手术KO小鼠和假手术野生型（WT）小鼠的心功能没有差异，但KO小鼠在压力过载时表现出高于WT小鼠的左心室压力和更好的收缩功能。Northern blot分析显示，压力过载导致WT小鼠左心室肌浆网Ca^<2+>- atp酶（SERCA2） mRNA水平降低，而KO小鼠则没有。与WT小鼠相比，KO小鼠间质纤维化的增生性变化更为明显。这些结果表明，NCX的减少会导致心功能异常，并在压力过载的情况下导致明显的心脏肥大。

The Na^+-Ca^<2+> exchanger (NCX) on the plasma membrane is thought to be the main calcium extrusion system from the cytosol to the extracellular space in many mammalian excitable cells including cardiac myocytes. Three mammalian isoforms of NCX (NCX1, NCX2 and NCX3) have been isolated and NCX1 is expressed at high levels in the heart. However, the pathophysiological role of NCX in the heart is still unclear because of lack of specific inhibitors of NCX. To determine the role of NCX in cardiac contraction and the development of cardiac hypertrophy, we imposed pressure overload on the heart of heterozygous NCX knockout (KO) mice by constricting transverse aorta and examined cardiac function and morphology at three weeks after operation. Although there was no difference in cardiac function between sham-operated KO mice and sham-operated wild type (WT) mice, KO mice showed higher left ventricular pressure, and better systolic function than WT mice in response to pressure overload. Northern blot analysis revealed that mRNA levels of sarcoplasmic reticulum Ca^<2+>-ATPase (SERCA2) were reduced by pressure overload in left ventricles of WT mice but not of KO mice. Hypertrophic changes with interstitial fibrosis were more prominent in KO mice than WT mice. These results suggest that reduction of NCX results in supernormalized cardiac function and causes marked cardiac hypertrophy in response to pressure overload.