Connexins and atrial fibrillation: filling in the gaps.

Atrial fibrillation (AF) is an extremely common arrhythmia with important consequences and presently suboptimal therapeutic options.1 A great deal of research has been performed to understand the detailed mechanisms of AF, with the hope that a better appreciation of the fundamental determinants of arrhythmogenesis will lead to the development of novel, more successful treatment possibilities.2 Article see p 216 One aspect of AF pathophysiology that has elicited great interest has been changes in gap junction/connexin physiology. An important role for altered gap junction function and the potential importance of gap junctions as a therapeutic target for AF were first emphasized by Spach and Starmer over 15 years ago.3 Since that time, our understanding of gap junction physiology, biophysics, and molecular biology has increased enormously,4,5 as have studies on their role in AF pathogenesis and management.2 Gap junctions contain transmembrane ion-channel proteins called connexins (Figure,panel A). Connexons (containing 6 connexin molecules each) in the gap junctions of adjacent cardiomyocytes line up and attach, transferring ions or molecules <1 kDa freely between cells, coupling them electrically (Figure, panel B). Cardiac tissues express a variety of connexins, including connexin (Cx)40, Cx43, Cx45, Cx30.2/31.9, and Cx37,5 with all but Cx37 present in cardiomyocytes and the most important connexins in atrial tissue being Cx40 and Cx43. There is evidence that posttranslational modification, particularly connexin phosphorylation, is important in governing connexin localization and function.6 Figure. A , Connexons contain 6 connexins each, arranged in a circle. Connexins …