Alterations in Intercalated Disk Proteins Contribute to the Development of Lethal Arrhythmias

闰盘（ID）含有粘附连接（AJs）和连接蛋白（Cx）间隙连接（GJs）。我们研究了UM-X7.1心肌病仓鼠（UMX）心力衰竭发展过程中的ID重塑。我们研究了血管紧张素II阻断剂（ARB）对ID重塑的影响。10 w时，约20%的UMX突然死亡，约30%的UMX可诱导VT/VF。10 w时动作电位时程离散度增大。20周时心脏空间常数明显减小，传导速度减慢，APD离散度增加。20周时Cx43表达减少，Ser 255磷酸化Cx43表达增加。Cx43的定性和定量改变产生严重的致瘤底物。β-连环蛋白的变化先于Cx43的改变。10周时，β-catenin在细胞核的表达明显减少。ARB改善了ID蛋白和生理特性的这些改变。 ARB是ID重塑的有效治疗方法。

The intercalated disc (ID) contains adhesion junctions (AJs) and connexin (Cx) gap junctions (GJs). We investigated ID remodeling during development of heart failure in UM-X7.1 cardiomyopathic hamsters (UMX). We investigated the effect of angiotensin II blockade (ARB) on ID remodeling. At 10w, ~20% of UMX died suddenly, and VT/VF was inducible in ~30%. At 10w, the dispersion of action potential duration (APD) was increased. At 20w showed significant reduction of cardiac space constant, a decrease in conduction velocity, and an increase in APD dispersion. The expression of Cx43 was reduced and Ser255-phosphorylated Cx43 was increased at 20w. Qualitative and quantitative Cx43 alterations create serious arrhythmogenic substrate. The changes in beta-catenin preceded Cx43 alterations. At 10w, the nuclear expression of beta-catenin was remarkably decreased. ARB improved these alterations in ID proteins and physiological properties. ARB was an effective treatment of ID remodeling.