The intercalated disc is an important structure in cardiomyocytes, as it is essential to maintain correct contraction and proper functioning of the heart. Adhesion and communication between cardiomyocytes are mediated by three main types of intercellular junctions, all residing in the intercalated disc: gap junctions, desmosomes and the areae compositae. Mutations in genes that encode junctional proteins, including αT-catenin (encoded by CTNNA3), have been linked to arrhythmogenic cardiomyopathy and sudden cardiac death. In mice, the loss of αT-catenin in cardiomyocytes leads to impaired heart function, fibrosis, changed expression of desmosomal proteins and increased risk for arrhythmias following ischemia-reperfusion. Currently, it is unclear how the intercalated disc and the intercellular junctions are organized in 3D in the hearts of this αT-catenin knockout (KO) mouse model. In order to scrutinize this, ventricular cardiac tissue of αT-catenin KO mice was used for volume electron microscopy (VEM), making use of Focused Ion Beam Scanning Electron Microscopy (FIB-SEM), allowing a careful 3D reconstruction of the intercalated disc, including gap junctions and desmosomes. Although αT-catenin KO and control mice display a comparable organization of the sarcomere and the different intercalated disc regions, the folds of the plicae region of the intercalated disc are longer and more narrow in the KO heart, and the pale region between the sarcomere and the intercalated disc is larger. In addition, αT-catenin KO intercalated discs appear to have smaller gap junctions and desmosomes in the plicae region, while gap junctions are larger in the interplicae region of the intercalated disc. Although the reason for this remodeling of the ultrastructure after αT-catenin deletion remains unclear, the excellent resolution of the FIB-SEM technology allows us to reconstruct details that were not reported before. This article is protected by copyright. All rights reserved.

中文翻译：

---

通过使用 FIB-SEM 揭示心肌细胞之间缺乏 αT-连环蛋白的细胞-细胞接触的超微结构细节

插入的椎间盘是心肌细胞的重要结构，因为它对于维持心脏的正确收缩和正常功能至关重要。心肌细胞之间的粘附和通讯由三种主要类型的细胞间连接介导，所有类型都位于插入的椎间盘中：间隙连接、桥粒和复合区。编码连接蛋白的基因突变，包括 αT-catenin（由 CTNNA3 编码），与致心律失常性心肌病和心源性猝死有关。在小鼠中，心肌细胞中 αT-catenin 的缺失会导致心脏功能受损、纤维化、桥粒蛋白表达改变以及缺血再灌注后心律失常的风险增加。目前，目前尚不清楚在这种 αT-连环蛋白敲除 (KO) 小鼠模型的心脏中，插入的椎间盘和细胞间连接是如何以 3D 方式组织的。为了仔细检查这一点，αT-catenin KO 小鼠的心室心脏组织被用于体积电子显微镜 (VEM)，利用聚焦离子束扫描电子显微镜 (FIB-SEM)，允许对插入的椎间盘进行仔细的 3D 重建，包括间隙连接和桥粒。尽管 αT-catenin KO 小鼠和对照小鼠的肌节组织和不同的椎间盘插入区域具有可比性，但在 KO 心脏中，插入椎间盘的 plicae 区域的褶皱更长更窄，肌节和肌节之间的苍白区域插入的圆盘更大。此外，αT-catenin KO 插入椎间盘似乎在 plicae 区域具有较小的间隙连接和桥粒，而在插入椎间盘的 interplicae 区域中间隙连接较大。尽管αT-连环蛋白缺失后超微结构重塑的原因尚不清楚，但FIB-SEM技术的出色分辨率使我们能够重建以前未报道的细节。本文受版权保护。版权所有。