title: Gap junction alterations in human cardiac disease.
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 regular rhythm of the healthy heart. As in most tissues and organs, multiple connexin types are expressed in the heart; connexin43, connexin40 and connexin45 are found in distinctive combinations and relative quantities in different, functionally specialized subsets of cardiomyocyte. Alterations of gap junction organization and connexin expression are now well established as a consistent feature of human heart disease in which there is an arrhythmic tendency. These alterations may take the form of structural remodelling, involving disturbances in the distribution of gap junctions and/or alteration of the amount or type of connexin(s) expressed. In the diseased ventricles, the most consistent quantitative alteration involves heterogeneous reduction in connexin43 expression. In the atria, features of gap organization and connexin expression have been implicated in the initiation of atrial fibrillation and, once the condition becomes chronic, gap junction alterations associated with remodelling may contribute to persistence of the condition. By correlating data from studies on the human patient with those from animal and cell models, alterations in gap junctions and connexins have emerged as important factors to be considered in understanding the pro-arrhythmic substrate found in a variety of forms of heart disease.
authors.affiliation: Cardiac Medicine, National Heart and Lung Institute, Imperial College Faculty of Medicine, Guy Scadding Building, Dovehouse Street, London SW3 6LY, UK. n.severs@imperial.ac.uk
authors.forename: Nicholas J
authors.initials: NJ
authors.lastname: Severs
authors.forename: Steven R
authors.initials: SR
authors.lastname: Coppen
authors.forename: Emmanuel
authors.initials: E
authors.lastname: Dupont
authors.forename: Hung-I
authors.initials: HI
authors.lastname: Yeh
authors.forename: Yu-Shien
authors.initials: YS
authors.lastname: Ko
authors.forename: Tsutomu
authors.initials: T
authors.lastname: Matsushita
mesh_terms: D000818:Animals; D002450:Cell Communication; D017630:Connexins / Q000502:physiology*; D004594:Electrophysiology; D017629:Gap Junctions / Q000502:physiology*; D006321:Heart / Q000503:physiopathology*; D006331:Heart Diseases / Q000503:physiopathology*; D006801:Humans; D020257:Ventricular Remodeling
chemical_list: D017630:Connexins