title: NaV1.5 and interacting proteins in human arrhythmogenic cardiomyopathy.
abstract: Evaluation of: Noorman M, Hakim S, Kessler E et al. Remodeling of the cardiac sodium channel, connexin43, and plakoglobin at the intercalated disk in patients with arrhythmogenic cardiomyopathy. Heart Rhythm 10(3), 412-419 (2013). Arrhythmogenic cardiomyopathy (AC) is a heart muscle disease characterized by a progressive replacement of the ventricular myocardium with adipose and fibrous tissue. This disease is often associated with mutations in genes encoding desmosomal proteins in the majority of patients. Based on results obtained from recent experimental models, a disturbed distribution of gap junction proteins and cardiac sodium channels may also be observed in AC phenotypes, secondary to desmosomal dysfunction. The study from Noorman et al. examined heart sections from patients diagnosed with AC and performed immunohistochemical analyses of N-cadherin, PKP2, PKG, Cx43 and the cardiac sodium channel NaV1.5. Altered expression/distribution of Cx43, PKG and NaV1.5 was found in most cases of patients with AC. The altered expression and/or distribution of NaV1.5 channels in AC hearts may play a mechanistic role in the arrhythmias leading to sudden cardiac death in AC patients. Thus, NaV1.5 should be considered as a supplemental element in the evaluation of risk stratification and management strategies. However, additional experiments are required to clearly understand the mechanisms leading to AC phenotypes.
authors.affiliation: Department of Clinical Research, Ion Channel Research Group, University of Bern, Murtenstrasse 35, 3010 Bern, Switzerland.
authors.forename: Ludovic
authors.initials: L
authors.lastname: Gillet
authors.forename: Diana
authors.initials: D
authors.lastname: Shy
authors.forename: Hugues
authors.initials: H
authors.lastname: Abriel
mesh_terms: D019571:Arrhythmogenic Right Ventricular Dysplasia / Q000235:genetics*; D018031:Connexin 43 / Q000235:genetics*; D004247:DNA / Q000235:genetics*; D005260:Female; D006801:Humans; D008297:Male; D009154:Mutation; D032383:Myocytes, Cardiac / Q000378:metabolism*; D015222:Sodium Channels / Q000235:genetics*; D051185:gamma Catenin / Q000235:genetics*
chemical_list: D018031:Connexin 43; D015222:Sodium Channels; D051185:gamma Catenin; D004247:DNA