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. 2007 May 1;5(4):355–366. doi: 10.1111/j.1582-4934.2001.tb00170.x

Gap junction remodeling and cardiac arrhythmogenesis: cause or coincidence?

Nicholas J Severs 1,✉
PMCID: PMC6740299  PMID: 12067469

Abstract

Gap junctions, clusters of transmembrane channels that link adjoining cells, mediate myocyte‐to‐myocyte electrical coupling and communication. The component proteins of gap junction channels are termed connexins and, in in vitro expression systems, gap‐junctional channels composed of different connexin types exhibit different biophysical properties. In common with other tissues, the heart expresses multiple connexin isoforms. Spatially defined patterns of expression of three connexin isoforms ‐ connexin43, connexin40 and connexin45 ‐ form the cell‐to‐cell conduction pathways responsible for the orderly spread of current flow that governs the normal cardiac rhythm. Remodeling of gap junction organization and connexin expression is a common feature of human heart disease conditions in which there is an arrhythmic tendency. This remodeling may take the form of disturbances in the distribution of gap junctions and/or quantitative alterations in connexin expression, notably reduced ventricular connexin43 levels. The idea that such changes may contribute to the development of a pro‐arrhythmic substrate in the diseased heart has gained ground over the last decade. Recent studies using transgenic mice models have raised new opportunities to explore the significance of gap junction remodeling in the diseased heart.

Keywords: cardiomyocyte, gap junctions, connexins, intercellular communication

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