title: Functional consequences of abnormal Cx43 expression in the heart.
abstract: The major gap junction protein expressed in the heart, connexin43 (Cx43), is highly remodeled in the diseased heart. Usually, Cx43 is down-regulated and heterogeneously redistributed to the lateral sides of cardiomyocytes. Reverse remodeling of the impaired Cx43 expression could restore normal cardiac function and normalize electrical stability. In this review, the reduced and heterogeneous Cx43 expression in the heart will be addressed in hypertrophic, dilated and ischemic cardiomyopathy together with its functional consequences of conduction velocity slowing, dispersed impulse conduction, its interaction with fibrosis and propensity to generate arrhythmias. Finally, different therapies are discussed. Treatments aimed to improve the Cx43 expression levels show new potentially anti-arrhythmic therapies during heart failure, but those in the context of acute ischemia can be anti-arrhythmogenic at the cost of larger infarct sizes. This article is part of a Special Issue entitled: The Communicating junctions, composition, structure and characteristics.
authors.affiliation: Department of Medical Physiology, University Medical Center, Utrecht, The Netherlands.
authors.forename: Magda S C
authors.initials: MS
authors.lastname: Fontes
authors.forename: Toon A B
authors.initials: TA
authors.lastname: van Veen
authors.forename: Jacques M T
authors.initials: JM
authors.lastname: de Bakker
authors.forename: Harold V M
authors.initials: HV
authors.lastname: van Rijen
mesh_terms: D000818:Animals; D001145:Arrhythmias, Cardiac / Q000378:metabolism; D009202:Cardiomyopathies / Q000378:metabolism; D002311:Cardiomyopathy, Dilated / Q000378:metabolism; D002312:Cardiomyopathy, Hypertrophic / Q000378:metabolism; D018031:Connexin 43 / Q000096:biosynthesis* / Q000502:physiology*; D005355:Fibrosis / Q000473:pathology; D017629:Gap Junctions / Q000378:metabolism; D005786:Gene Expression Regulation; D006321:Heart / Q000502:physiology*; D006801:Humans; D008954:Models, Biological; D017202:Myocardial Ischemia / Q000378:metabolism; D009206:Myocardium / Q000378:metabolism*
chemical_list: D018031:Connexin 43