Cardiac sodium channelopathy associated with SCN5A mutations: electrophysiological, molecular and genetic aspects.

Abstract

Over the last two decades, an increasing number of SCN5A mutations have been described in patients with long QT syndrome type 3 (LQT3), Brugada syndrome, (progressive) conduction disease, sick sinus syndrome, atrial standstill, atrial fibrillation, dilated cardiomyopathy, and sudden infant death syndrome (SIDS). Combined genetic, electrophysiological and molecular studies have provided insight into the dysfunction and dysregulation of the cardiac sodium channel in the setting of SCN5A mutations identified in patients with these inherited arrhythmia syndromes. However, risk stratification and patient management is hindered by the reduced penetrance and variable disease expressivity in sodium channelopathies. Furthermore, various SCN5A-related arrhythmia syndromes are known to display mixed phenotypes known as cardiac sodium channel overlap syndromes. Determinants of variable disease expressivity, including genetic background and environmental factors, are suspected but still largely unknown. Moreover, it has become increasingly clear that sodium channel function and regulation is more complicated than previously assumed, and the sodium channel may play additional, as of yet unrecognized, roles in cardiac structure and function. Development of cardiac structural abnormalities secondary to SCN5A mutations has been reported, but the clinical relevance and underlying mechanisms are unclear. Increased insight into these issues would enable a major next step in research related to cardiac sodium channel disease, ultimately enabling improved diagnosis, risk stratification and treatment strategies.

• Authors: Carol Ann Remme
• Journal: The Journal of physiology (J Physiol) Vol. 591 Issue 17 Pg. 4099-116 (Sep 01 2013) ISSN: 1469-7793 [Electronic] England
• PMID: 23818691 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't, Review)

Chemical References

• NAV1.5 Voltage-Gated Sodium Channel
• SCN5A protein, human

Topics

• Action Potentials
• Animals
• Brugada Syndrome (genetics, metabolism, physiopathology)
• Channelopathies (genetics, metabolism, physiopathology)
• Humans
• Long QT Syndrome (genetics, metabolism, physiopathology)
• Mutation
• NAV1.5 Voltage-Gated Sodium Channel (genetics, metabolism)