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.
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.
Authors: Philippe Beauchamp; Cécile Choby; Thomas Desplantez; Karin de Peyer; Karen Green; Kathryn A Yamada; Robert Weingart; Jeffrey E Saffitz; André G Kléber Journal: Circ Res Date: 2004-06-10 Impact factor: 17.367
Authors: Halina S Chkourko; Guadalupe Guerrero-Serna; Xianming Lin; Nedal Darwish; Joshua R Pohlmann; Keith E Cook; Jeffrey R Martens; Eli Rothenberg; Hassan Musa; Mario Delmar Journal: Heart Rhythm Date: 2012-03-07 Impact factor: 6.343
Authors: Thomas Desplantez; Megan L McCain; Philippe Beauchamp; Ghislaine Rigoli; Barbara Rothen-Rutishauser; Kevin Kit Parker; Andre G Kleber Journal: Cardiovasc Res Date: 2012-01-27 Impact factor: 10.787