Editorials |
From the Institute for Cardiovascular Research (S.M.T., J.J.), Departments of Microbiology and Immunology (S.M.T.) and Pharmacology (J.J.), SUNY Upstate Medical University, Syracuse, NY.
Correspondence to José Jalife, MD, Department of Pharmacology, SUNY Upstate Medical University, 766 Irving Ave, Syracuse, NY 13210. E-mail jalifej@upstate.edu
Key Words: gap junctions conduction velocity connexin40 connexin45 atria
An extract of the first 250 words of the full text is provided, because this article has no abstract. |
Manipulation of the expression of specific genes in transgenic or knockout (KO) mice has become an important strategy to study the biological and physiological roles of individual cardiac proteins.13 Several laboratories using transgenic and knockout methodologies have made substantial progress in generating mouse models with reduced connexin expression in the heart. This has provided the unique opportunity to characterize both qualitatively and quantitatively the role of cardiac gap junction channels in electrical wave propagation and has opened many interesting questions regarding the electrophysiological consequences and proarrhythmic effects of reduced intercellular coupling in the atria, ventricles, and His-Purkinje system of neonatal and/or adult mice lacking a given connexin.
The current count of 19 connexins in the mouse genome and 20 connexins in the human genome4 implies a highly intriguing diversity of connexin function. But the exact nature of that diversity is not clear. Connexins can no longer be looked at as passive pores that allow ions to pass from one cell to the next. At the least, these channels are dynamic pores that are regulated by a distinct pattern of cellular states and protein interactions. It is likely that these channels are more than that. Connexins are in many ways similar to scaffolding proteins that can bind cytoskeletal proteins,5 protein kinases,69 and cellular scaffolds.10,11 Recent evidence has even suggested that some of the biological properties of connexin channels are distinct from their pore ability to form gap junctions and pass electrical information from one cell to the next.12,13 Based on the
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M. M. Kreuzberg, G. Sohl, J.-S. Kim, V. K. Verselis, K. Willecke, and F. F. Bukauskas Functional Properties of Mouse Connexin30.2 Expressed in the Conduction System of the Heart Circ. Res., June 10, 2005; 96(11): 1169 - 1177. [Abstract] [Full Text] [PDF] |
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