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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. [Copyright &y& Elsevier]

We set out to develop an in vitro cell model in which connexins 43, 40 and 45 are co-expressed in the same combinations as found in different sub-types of cardiomyocyte in vivo , using inducible promoters of the Tet-Off and Ecdysone systems. In initial studies, a heterogeneous pattern of gene expression was observed. To achieve homogeneous expression, an Internal Ribosome Entry Site (IRES) sequence was employed, ensuring that a single mRNA coded for connexin and antibiotic resistance. We then constructed plasmids that combine the inducibility of the Tet-Off and Ecdysone systems with the homogeneous expression given by the IRES constructs. These were demonstrated to give inducible and homogeneous expression. By using the reporter gene, Enhanced Green Fluorescent Protein (EGFP), it was further shown in the Tet-Off system that expression of the transfected gene was modulated homogeneously in all cells when induction was repressed. The cell model is now at a suitable stage of development for investigation of the functional correlates of the distinctive connexin co-expression found in different regions of the heart. [ABSTRACT FROM AUTHOR]

Objective: Intercellular coupling through gap junctions allows the morphologically and functionally heterogeneous sinoatrial node to synchronize and drive the atrial muscle. The purpose of this study was to identify the connexin isotypes expressed by sinoatrial node cells and to analyse the density of connexins in relation to cell size. Methods: Labeling for the different connexins using isotype-specific antibodies was assessed in cells isolated from the rabbit sinoatrial node by immunoconfocal microscopy. Results: Sinoatrial node cells with a cell projection area smaller than 800 μm2 were devoid of immunolabeling for connexin43. Such small cells showed high levels of connexin45 labeling (compared to that in large cells) and low levels of connexin40 labeling. Sinoatrial node cells with a projection area between 800 and 1200 μm2 had a lower amount of connexin45 label and again a small amount of connexin40 but an increased amount of connexin43 label. In the larger sinoatrial node cells, some colocalization of connexin45 and connexin43 immunolabeled spots was observed. Conclusions: Rabbit sinoatrial node cells are heterogeneous in terms of connexin expression, and there is a clear cell size-dependence in pattern of connexin expression. Small (putative central) cells express connexin45 but not connexin43, whereas larger (putative peripheral) cells express both connexin45 and connexin43. The co-localization of connexin43 and connexin45 in larger cells raises the possibility that heterotypic or heteromeric connexin43/connexin45 channels could be present in gap junctions at the periphery of the sinoatrial node. [ABSTRACT FROM PUBLISHER]

Discusses the diversity of connexin expression patterns in the atrioventricular (AV) node. Use of transgenic mice in connexin research; Significance of the AV node in the transfer and timing of impulse transmission from atria to ventricles; Information on the types of connexins in the heart.