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Loss of Plakophilin-2 Expression Leads to Decreased Sodium Current and Slower Conduction Velocity in Cultured Cardiac Myocytes

Overview
Journal Circ Res
Specialty Cardiology & Vascular Diseases
Date 2009 Aug 8
PMID 19661460
Citations 160
Authors
Priscila Y Sato
Hassan Musa
Wanda Coombs
Guadalupe Guerrero-Serna
Gustavo A Patino
Steven M Taffet
Lori L Isom
Mario Delmar
Affiliations
Soon will be listed here.
Abstract

Rationale: Plakophilin-2 (PKP2) is an essential component of the cardiac desmosome. Recent data show that it interacts with other molecules of the intercalated disc. Separate studies show preferential localization of the voltage-gated sodium channel (Na(V)1.5) to this region.

Objective: To establish the association of PKP2 with sodium channels and its role on action potential propagation.

Methods And Results: Biochemical, patch clamp, and optical mapping experiments demonstrate that PKP2 associates with Na(V)1.5, and that knockdown of PKP2 expression alters the properties of the sodium current, and the velocity of action potential propagation in cultured cardiomyocytes.

Conclusions: These results emphasize the importance of intermolecular interactions between proteins relevant to mechanical junctions, and those involved in electric synchrony. Possible relevance to the pathogenesis of arrhythmogenic right ventricular cardiomyopathy is discussed.

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