Functional consequences of abnormal Cx43 expression in the heart

• Published in: Biochimica et biophysica acta 2012-08, Vol.1818 (8), p.2020-2029
• Main Authors: Fontes, Magda S.C., van Veen, Toon A.B., de Bakker, Jacques M.T., van Rijen, Harold V.M.
• Format: Article
• Language: English
• Subjects: Animals; Arrhythmia; Arrhythmias, Cardiac - metabolism; Cardiomyopathies - metabolism; Cardiomyopathy, Dilated - metabolism; Cardiomyopathy, Hypertrophic - metabolism; Conduction velocity; Connexin 43 - biosynthesis; Connexin 43 - physiology; Connexin43; Fibrosis; Fibrosis - pathology; Gap Junctions - metabolism; Gene Expression Regulation; Heart - physiology; Heterogeneity; Humans; Models, Biological; Myocardial Ischemia - metabolism; Myocardium - metabolism
• ISSN: 0005-2736; 0006-3002; 1879-2642
• DOI: 10.1016/j.bbamem.2011.07.039

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. ► Review on the remodeling of cardiac ventricular gap junctions and its consequences. ► Heart remodeling results in heterogeneity and dephosphorylation of Cx43 expression. ► Consequences of abnormal Cx43 expression for the development of arrhythmias. ► Therapies aimed to improve the Cx43 expression levels, reduced arrhythmogenesis.