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: Marina Cerrone, Mario Delmar
• Journal: Trends in cardiovascular medicine (Trends Cardiovasc Med) Vol. 24 Issue 5 Pg. 184-90 (Jul 2014) ISSN: 1873-2615 [Electronic] United States
• PMID: 24656989 (Publication Type: Journal Article, Review)
• Copyright: Copyright © 2014 Elsevier Inc. All rights reserved.

Chemical References

• PKP2 protein, human
• Plakophilins
• Sodium Channels

Topics

• Action Potentials
• Animals
• Arrhythmogenic Right Ventricular Dysplasia (genetics, metabolism, physiopathology)
• Brugada Syndrome (genetics, metabolism, physiopathology)
• Desmosomes (metabolism)
• Genetic Predisposition to Disease
• Heart Rate (genetics)
• Humans
• Mutation
• Phenotype
• Plakophilins (genetics, metabolism)
• Protein Transport
• Sodium Channels (genetics, metabolism)