The role of myocardial gap junctions in electrical conduction and arrhythmogenesis.
Electrical activation of the heart requires cell-cell transfer of current via gap junctions, arrays of densely packed protein channels that permit intercellular passage of ions and small molecules. Because current transfer occurs only at gap junctions, the spatial distribution and biophysical properties 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, individual cells express multiple connexins, which creates the potential for considerable functional diversity in gap junction channels. Although gap junction channels are relatively nonselective in their permeability to ions and small molecules, cardiac myocytes actively adjust their level of coupling by multiple mechanisms including changes in connexin expression, regulation of connexin trafficking and turnover, and modulation of channel properties. In advanced stages of heart disease, connexin expression and intercellular 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 proteins in normal cardiac function and arrhythmogenesis.
Kanno
S
S
Department of Surgery and the Center for Cardiovascular Research, Washington University School of Medicine, St. Louis, MO 63110, USA.
Saffitz
J E
JE
D000818:Animals; D001145:Arrhythmias, Cardiac / Q000209:etiology* / Q000503:physiopathology; D002450:Cell Communication; D017630:Connexins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D015536:Down-Regulation; D017629:Gap Junctions / Q000502:physiology* / Q000648:ultrastructure; D006329:Heart Conduction System / Q000502:physiology*; D006801:Humans; D005810:Multigene Family; D009206:Myocardium / Q000166:cytology / Q000648:ultrastructure; D011487:Protein Conformation; D015854:Up-Regulation
D017630:Connexins