title: Desmosomes and the sodium channel complex: implications for arrhythmogenic cardiomyopathy and Brugada syndrome.
abstract: Mutations in proteins of the desmosome are associated with arrhythmogenic cardiomyopathy (AC; also referred to as "ARVC" or "ARVD"). Life-threatening ventricular arrhythmias often occur in the concealed phase of the disease before the onset of structural changes. Among the various potential mechanisms for arrhythmogenesis in AC, in this article, we concentrate on the relation between desmosomes and sodium channel function. We review evidence indicating that (1) loss of desmosomal integrity (including mutations or loss of expression of plakophilin-2; PKP2) leads to reduced sodium current (INa), (2) the PKP2-INa relation could be partly consequent to the fact that PKP2 facilitates proper trafficking of proteins to the intercalated disc, and (3) PKP2 mutations can be present in patients diagnosed with Brugada syndrome (BrS), thus supporting the previously proposed notion that AC and BrS are not two completely separate entities, but "bookends" in a continuum of variable sodium current deficiency and structural disease.
authors.affiliation: Leon H. Charney Division of Cardiology, New York University School of Medicine, 522 First Avenue, SRB 806, New York, NY 10016.
authors.forename: Marina
authors.initials: M
authors.lastname: Cerrone
authors.affiliation: Leon H. Charney Division of Cardiology, New York University School of Medicine, 522 First Avenue, SRB 806, New York, NY 10016. Electronic address: Mario.delmar@nyumc.org.
authors.forename: Mario
authors.initials: M
authors.lastname: Delmar
mesh_terms: D000200:Action Potentials; D000818:Animals; D019571:Arrhythmogenic Right Ventricular Dysplasia / Q000235:genetics / Q000378:metabolism* / Q000503:physiopathology; D053840:Brugada Syndrome / Q000235:genetics / Q000378:metabolism* / Q000503:physiopathology; D003896:Desmosomes / Q000378:metabolism*; D020022:Genetic Predisposition to Disease; D006339:Heart Rate / Q000235:genetics; D006801:Humans; D009154:Mutation; D010641:Phenotype; D051191:Plakophilins / Q000235:genetics / Q000378:metabolism*; D021381:Protein Transport; D015222:Sodium Channels / Q000235:genetics / Q000378:metabolism*
chemical_list: C495337:PKP2 protein, human; D051191:Plakophilins; D015222:Sodium Channels