心肌细胞缝隙连接重塑与心律失常.doc

586 生理学报 Acta Physiologica Sinica, December 25, 2011, 63(6): 586–592 综 述 余志斌*，圣娟娟 第四军医大学航空航天生理学教研室，西安 710032 摘 要：缝隙连接是相邻心肌细胞间电、化学偶联的通道，亦是心室肌成为功能性合胞体的重要结构。心肌有缝隙连接蛋白 (connexin, CX) 40、43与45的表达，心室肌主要表达CX43。CX43形成的缝隙连接大部分呈点状分布于闰盘部位，心肌细胞 膜侧面分布极少。心肌缺血-再灌注、肥厚、衰竭、高胆固醇与糖尿病条件下，心肌细胞缝隙连接均发生重塑。由以上疾病 引起的重塑特征相似，均为CX43表达降低合并非均匀化、侧面化与去磷酸化。研究显示，这些重塑变化与心肌局部血管紧 张素II浓度升高有关。缝隙连接CX43表达降低合并非均匀化改变电传导的各向异性，降低电传导速率。缝隙连接CX43的去 磷酸化，不仅减慢缝隙连接电传导速度，而且降低其通透性。而侧面化的缝隙连接，可能使CX43形成的半通道增多，导致 ATP外流与Na+内流，引起延迟后去极化。心肌病理条件下CX43的这些重塑，构成心律失常的基础。本文就心肌细胞缝隙连 接重塑与心律失常的关系研究进展作一综述。 关键词：心肌细胞；缝隙连接；缝隙连接蛋白43；重塑 中图分类号：R331.3+1 Remodeling of cardiac gap junctions and arrhythmias YU Zhi-Bin*, SHENG Juan-Juan Department of Aerospace Physiology, the Fourth Military Medical University, Xi’an 710032, China Abstract: In the heart, gap junctions mediate electrical and chemical coupling between adjacent cardiomyocytes, forming the cell-to- cell pathways for orderly spread of the wave of electrical excitation responsible for a functional syncytium. Three principal connexins are expressed in cardiomyocytes, connexin 43 (CX43), CX40, and CX45. CX43 predominates in ventricular muscle cells. Most of the gap junctions, assembled from CX43, are located at the intercalated discs, often with larger junctional plaques at the disc periphery. The gap junctions are rarely distributed to the sides of the cardiomyocyte. The ischemia-reperfusion, cardiac hypertrophy, heart fail- ure, hypercholesterolemia, and diabetes mellitus induce gap junction remodeling. The gap junction remodeling induced by above- mentioned diseases shows similar characteristics, including down-regulation of CX43, reduction in gap junction plaque size, increased heterogeneity and lateralization of gap junction distribution, and dephosphorylation of CX43. The elevated angiotensin II concentra- tion in local myocardium may play an important role in the gap junction remodeling. The down-regulation of CX43 and lateralization of gap junction distribution alter anisotropic s