Channelopathies from mutations in the cardiac sodium channel protein complex

Abstract

The cardiac sodium current underlies excitability in heart, and inherited abnormalities of the proteins regulating and conducting this current cause inherited arrhythmia syndromes. This review focuses on inherited mutations in non-pore forming proteins of sodium channel complexes that cause cardiac arrhythmia, and the deduced mechanisms by which they affect function and dysfunction of the cardiac sodium current. Defining the structure and function of these complexes and how they are regulated will contribute to understanding the possible roles for this complex in normal and abnormal physiology and homeostasis. This article is part of a Special Issue entitled "Na(+) Regulation in Cardiac Myocytes".

Keywords: Arrhythmia; Brugada Syndrome; Long QT syndrome; SCN5A; SIDS; Sodium current.

Figure 1

SCCP representations of a Syntrophin Complex (A,D), a CaMKinase II Complex, (B,E), and a Caveolin-3 Complex (C,F). Top panels: Atomic scale resolution representations highlighting functionally associated sub-complexes. Bottom panels: Diagrams of the panels above. For construction of the top panels each protein (or if not available, a matched homologue) was accessed from the Research Collaboratory for Structural Bioinformatics Protein Data Bank (http://www.rcsb.org). Assembly was done manually taking into account known interactions sites. These renditions are intended to give impressions of relative size, shapes, and attachments and do not represent any energy minimization or other rigorous modeling. Additional details are in the online supplement.