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(Circulation Research. 2000;87:835.)
© 2000 American Heart Association, Inc.

Editorial

Connexin-40, Bundle-Branch Block, and Propagation at the Purkinje-Myocyte Junction

Jeffrey E. Saffitz, Richard B. Schuessler

From the Departments of Pathology and Surgery and the Center for Cardiovascular Research, Washington University, St. Louis, Mo.

Correspondence to Jeffrey E. Saffitz, MD, PhD, Department of Pathology, Box 8118, Washington University School of Medicine, 660 S Euclid Ave, St. Louis, MO 63110. E-mail saffitz@pathology.wustl.edu

Key Words: optical mapping • knockout mice • connexin40

	Introduction

 
Genetic engineering in mice has created unprecedented opportunities to define the contributions of specific proteins in complex cardiological processes, but these opportunities also present significant challenges in characterizing murine cardiac function and relating insights gained into the human heart. These challenges are especially keen in defining electrophysiological phenotypes. Elucidation of the role of specific gene products in impulse propagation or arrhythmogenesis in mice requires advanced technology, particularly if the gene of interest is expressed in a restricted pattern or distribution. Such is the case in the study by Tamaddon et al¹ appearing in this issue of Circulation Research.

This study is focused on connexin40 (Cx40), a protein that forms gap junction channels responsible for intercellular current flux. Cx40 expression in the adult heart is restricted to atrial myocytes, coronary vascular endothelium, and the His-Purkinje system. In addition to Cx40, cardiac myocytes express 2 other connexins, Cx43 and Cx45, in different amounts and combinations. A major goal of present research is to understand the biological roles of individual connexins.

Previously, Simon et al² from Harvard and Kirchhoff et al³ from the University of Bonn independently produced Cx40 knockout mice and characterized phenotypes by electrocardiography. As predicted by the pattern of Cx40 distribution, Cx40^-/- mice show prolongation of the PR interval and evidence of bundle branch block.^{2 3 4} However, going the next step to define mechanisms responsible for these alterations in the surface ECG requires a more sophisticated approach, and this is the basis for the study by Tamaddon et al.¹ These . . . [Full Text of this Article]

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