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

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 (NaV1.5) to this region. OBJECTIVE:To establish the...

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Bibliographic Details
Published in:Circulation research 2009-09, Vol.105 (6), p.523-526
Main Authors: Sato, Priscila Y, Musa, Hassan, Coombs, Wanda, Guerrero-Serna, Guadalupe, Patiño, Gustavo A, Taffet, Steven M, Isom, Lori L, Delmar, Mario
Format: Article
Language:English
Subjects:
Action Potentials
Animals
Arrhythmias, Cardiac - metabolism
Arrhythmias, Cardiac - pathology
Biological and medical sciences
Cardiac dysrhythmias
Cardiology. Vascular system
Cardiomyopathies - metabolism
Cardiomyopathies - pathology
Desmosomes - metabolism
Desmosomes - pathology
Fundamental and applied biological sciences. Psychology
Gene Expression Regulation
Gene Knockdown Techniques
Heart
Medical sciences
Myocytes, Cardiac - metabolism
Myocytes, Cardiac - pathology
NAV1.5 Voltage-Gated Sodium Channel
Plakophilins - metabolism
Rats
Rats, Sprague-Dawley
Sodium Channels - metabolism
Ventricular Dysfunction - metabolism
Ventricular Dysfunction - pathology
Vertebrates: cardiovascular system
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Summary: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 (NaV1.5) 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 NaV1.5, 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.
ISSN:0009-7330
1524-4571
DOI:10.1161/CIRCRESAHA.109.201418