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1、586生理学报ActaPhysiologicaSinica,December25,2011,63(6):586–592http://www.actaps.com.cn综综述述心心肌细胞缝隙连接重塑与心律失常肌细胞缝隙连接重塑与心律失常*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、
2、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。关关键词键词：心肌细胞；缝隙连
3、接；缝隙连接蛋白43；重塑中中图分类号图分类号：R331.3+1RemodelingofcardiacgapjunctionsandarrhythmiasYUZhi-Bin*,SHENGJuan-JuanDepartmentofAerospacePhysiology,theFourthMilitaryMedicalUniversity,Xi’an710032,ChinaAbstract:Intheheart,gapjunctionsmediateelectricalandchemicalcouplingbetweenadjacentcardiomyocytes,formingt
4、hecell-to-cellpathwaysfororderlyspreadofthewaveofelectricalexcitationresponsibleforafunctionalsyncytium.Threeprincipalconnexinsareexpressedincardiomyocytes,connexin43(CX43),CX40,andCX45.CX43predominatesinventricularmusclecells.Mostofthegapjunctions,assembledfromCX43,arelocatedattheintercalat
5、eddiscs,oftenwithlargerjunctionalplaquesatthediscperiphery.Thegapjunctionsarerarelydistributedtothesidesofthecardiomyocyte.Theischemia-reperfusion,cardiachypertrophy,heartfail-ure,hypercholesterolemia,anddiabetesmellitusinducegapjunctionremodeling.Thegapjunctionremodelinginducedbyabove-menti
6、oneddiseasesshowssimilarcharacteristics,includingdown-regulationofCX43,reductioningapjunctionplaquesize,increasedheterogeneityandlateralizationofgapjunctiondistribution,anddephosphorylationofCX43.TheelevatedangiotensinIIconcentra-tioninlocalmyocardiummayplayanimportantroleinthegapjunctionrem
7、odeling.Thedown-regulationofCX43andlateralizationofgapjunctiondistributionalteranisotropicspreadoftheimpulseofventricularmyocardium.ThedephosphorylationofCX43notonlyreduceselectricalconductance,butalsodecreasespermeabilityofchemicalsbetweencardiomy
