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Journal of Biomedicine and Biotechnology
Volume 2010, Article ID 624719, 14 pages
http://dx.doi.org/10.1155/2010/624719
Research Article

Ordered Assembly of the Adhesive and Electrochemical Connections within Newly Formed Intercalated Disks in Primary Cultures of Adult Rat Cardiomyocytes

1Division of Pediatric Cardiology, Department of Pediatrics and Communicable Diseases, University of Michigan, 1150 West Medical Center Dr., Ann Arbor, MI 48109, USA
2Department of Pathology, Feinberg School of Medicine, Northwestern University, 303 E. Chicago Avenue, Chicago, IL 60611, USA
3Department of Molecular and Integrative Physiology, University of Michigan, 1150 West Medical Center Dr., Ann Arbor, MI 48109, USA
4Department of Pharmacology, University of Michigan, 1150 West Medical Center Dr., Ann Arbor, MI 48109, USA
5Department of Cell and Developmental Biology, University of Michigan, 1150 West Medical Center Dr., Ann Arbor, MI 48109, USA
6Department of Internal Medicine, University of Michigan, 1150 West Medical Center Dr., Ann Arbor, MI 48109, USA

Received 21 November 2009; Accepted 17 February 2010

Academic Editor: Guy M. Benian

Copyright © 2010 Sarah B. Geisler et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Abstract

The intercalated disk (ID) is a complex structure that electromechanically couples adjoining cardiac myocytes into a functional syncitium. The integrity of the disk is essential for normal cardiac function, but how the diverse elements are assembled into a fully integrated structure is not well understood. In this study, we examined the assembly of new IDs in primary cultures of adult rat cardiac myocytes. From 2 to 5 days after dissociation, the cells flatten and spread, establishing new cell-cell contacts in a manner that recapitulates the in vivo processes that occur during heart development and myocardial remodeling. As cells make contact with their neighbors, transmembrane adhesion proteins localize along the line of apposition, concentrating at the sites of membrane attachment of the terminal sarcomeres. Cx43 gap junctions and ankyrin-G, an essential cytoskeletal component of voltage gated sodium channel complexes, were secondarily recruited to membrane domains involved in cell-cell contacts. The consistent order of the assembly process suggests that there are specific scaffolding requirements for integration of the mechanical and electrochemical elements of the disk. Defining the relationships that are the foundation of disk assembly has important implications for understanding the mechanical dysfunction and cardiac arrhythmias that accompany alterations of ID architecture.