The role of myocardial gap junctions in electrical conduction and arrhythmogenesis

Electrical activation of the heart requires cell-cell transfer of current v ia gap junctions, arrays of densely packed protein channels that permit int ercellular passage of ions and small molecules. Because current transfer oc curs only at gap junctions, the spatial distribution and biophysical proper ties of gap junction channels are important determinants of the conduction properties of cardiac muscle. Gap junction channels are composed of members of a multigene family of proteins called connexins. As a general rule, ind ividual cells express multiple connexins, which creates the potential for c onsiderable functional diversity in gap junction channels. Although gap jun ction channels are relatively nonselective in their permeability to ions an d small molecules, cardiac myocytes actively adjust their level of coupling by multiple mechanisms including changes in connexin expression, regulatio n of connexin trafficking and turnover, and modulation of channel propertie s. In advanced stages of heart disease, connexin expression and intercellul ar coupling are diminished, and gap junction channels become redistributed. These changes have been strongly implicated in the pathogenesis of lethal ventricular arrhythmias. Ongoing studies in genetically engineered mice are revealing insights into the role of individual gap junction channel protei ns in normal cardiac function and arrhythmogenesis. (C) 2001 Elsevier Scien ce Inc. All rights reserved.