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Review
. 2006:42:228-242.
doi: 10.1159/000092572.

Alterations in cardiac connexin expression in cardiomyopathies

Nicholas J Severs  1 , Emmanuel Dupont, Neil Thomas, Riyaz Kaba, Stephen Rothery, Revti Jain, Katherine Sharpey, Christopher H Fry
Affiliations
Review

Alterations in cardiac connexin expression in cardiomyopathies

Nicholas J Severs et al. Adv Cardiol. 2006.

Abstract

Gap junctions, assembled from connexins, form the cell-to-cell pathways for propagation of the precisely orchestrated patterns of current flow that govern the synchronized rhythm of the healthy heart. As in most tissues and organs, multiple connexin types are co-expressed in the heart; the connexins Cx43, Cx40 and Cx45 are found in distinctive combinations and relative quantities in different, functionally specialized subsets of cardiomyocytes. Alterations in connexin expression and gap junction organization, now a well-documented feature of human cardiomyopathies, potentially contribute to the pro-arrhythmic substrate. In the diseased ventricle, the most consistently reported quantitative alteration involves heterogeneous reduction in Cx43 expression and disruption of the normal ordered pattern of Cx43 gap junction distribution. Additional studies suggest that upregulation of Cx40 and Cx45 may also feature in the failing ventricle, the former restricted to ischemic cardiomyopathy and localized to the subendocardial region. By correlating data from studies on the human patient with those from animal and cell models, alterations in connexin expression and gap junction organization have emerged as important factors to be considered in understanding the pro-arrhythmic substrate found in human cardiomyopathies.

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