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(Circulation Research. 2005;96:485.)
© 2005 American Heart Association, Inc.

Editorial

Controlling the Gap

Myocytes, Matrix, and Mechanics

David D. Spragg, David A. Kass

From the Johns Hopkins Medical Institutions of Medicine and Cardiology, Johns Hopkins University School of Medicine, Baltimore, Md.

Correspondence to David A. Kass, MD, Johns Hopkins Medical Institutions, Ross 835, 720 Rutland St, Baltimore, MD 21205. E-mail dkass@jhmi.edu

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See related article, pages 558–566

Key Words: extracellular matrix • connexin43 • beta-integrins • mechanotransduction

An extract of the first 250 words of the full text is provided, because this article has no abstract.

Effective myocardial contraction depends in part on the efficient propagation of electrical signals through the tissue. The principal structure allowing for such rapid myocardial depolarization is the gap junction plaque, a collection of intercellular pores located primarily at intercalated discs. There, at myocyte poles, gap junctions function in close proximity to the complexes responsible for cell–cell tethering—desmosomes and fascia adherens junctions. Thus, the intercalated disc is the site of both intercellular coupling and adhesion. Gap junctions are formed by clusters of paired hexamers, one from each cell, which bridge to form a low-resistance intercellular channel facilitating the transmission of ions and small molecules (<1000 kD). Each hexamer (or connexon) is comprised of six individual connexins, a diverse protein family found in vascular, neural, and cardiac tissue. In humans, ventricular gap junctions are formed primarily from connexin43 (Cx43), a 43-kD protein encoded by chromosome 6.¹

Cx43 is a dynamic molecule, with rapid turnover (t_1/2 roughly 1 hour)² and responsiveness to a variety of mechanical and chemical stimuli. Myocyte connectivity, as mediated by gap junctions, depends not only on net expression of Cx43, but on effective translocation of Cx43 to the cell surface, the phosphorylation state of both Cx43 and associated proteins,³ and intracellular pH.⁴ Ventricular Cx43 net protein expression is downregulated in various cardiac disease conditions such as end-stage ischemic,⁵ idiopathic,⁵ hypertrophic,^1,6 and tachycardia-induced induced cardiomyopathies,⁷ myocardial ischemia and hibernation,⁸ and allograft rejection.⁹ Less is known, however, about posttranslational modification of Cx43 as a regulatory mechanism of gap junction function. Cx43 . . . [Full Text of this Article]

Related Article:

Matrix Protein–Specific Regulation of Cx43 Expression in Cardiac Myocytes Subjected to Mechanical Load

Amit J. Shanker, Kiyomi Yamada, Karen G. Green, Kathryn A. Yamada, and Jeffrey E. Saffitz
Circ. Res. 2005 96: 558-566. [Abstract] [Full Text] [PDF]

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