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(Circulation Research. 2007;101:703.)
© 2007 American Heart Association, Inc.

Cellular Biology

Connexin43 Remodeling Caused by Inhibition of Plakophilin-2 Expression in Cardiac Cells

Eva M. Oxford^*, Hassan Musa^*, Karen Maass, Wanda Coombs, Steven M. Taffet, Mario Delmar

From the Departments of Pharmacology (E.M.O., H.M., K.M., W.C., M.D.) and Microbiology and Immunology (S.M.T.), State University of New York, Upstate Medical University, Syracuse.

Correspondence to Mario Delmar, MD, PhD, Department of Pharmacology, SUNY Upstate Medical University, 766 Irving Ave, Syracuse NY 13210. E-mail delmarm{at}upstate.edu

Desmosomes and gap junctions are distinct structural components of the cardiac intercalated disc. Here, we asked whether the presence of plakophilin (PKP)2, a component of the desmosome, is essential for the proper function and distribution of the gap junction protein connexin (Cx)43. We used RNA silencing technology to decrease the expression of PKP2 in cardiac cells (ventricular myocytes, as well as epicardium-derived cells) obtained from neonatal rat hearts. We evaluated the content, distribution, and function of Cx43 gap junctions. Our results show that loss of PKP2 expression led to a decrease in total Cx43 content, a significant redistribution of Cx43 to the intracellular space, and a decrease in dye coupling between cells. Separate experiments showed that Cx43 and PKP2 can coexist in the same macromolecular complex. Our results support the notion of a molecular crosstalk between desmosomal and gap junction proteins. The results are discussed in the context of arrhythmogenic right ventricular cardiomyopathy, an inherited disease involving mutations in desmosomal proteins, including PKP2.

Key Words: adenovirus • arrhythmogenic right ventricular cardiomyopathy • connexin43 • gap junction • plakophilin 2

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