%0 Journal Article
%T Characterization of a novel Nav1.5 channel mutation, A551T, associated with Brugada syndrome
%A Kun-Chi Chiang
%A Ling-Ping Lai
%A Ru-Chi Shieh
%J Journal of Biomedical Science
%D 2009
%I BioMed Central
%R 10.1186/1423-0127-16-76
%X Brugada syndrome is a life-threatening, inherited arrhythmia disorder associated with autosomal dominant mutations in SCN5A [1-4], the gene encoding the human cardiac Na+ channel ¦Á subunit (Nav1.5) [5], which contains four homologous domains, each composed of six membrane-spanning segments, linked by cytoplasmic linkers. Brugada syndrome is characterized by a distinctive ST-segment elevation in the V1¨CV3 leads of the ECG that reflects abnormal electrical forces in the right ventricle [6], which are linked to SCN5A mutations causing reduced Nav1.5 function [5]. The discovery of SCN5A mutations in families with Brugada syndrome was first reported in 1998 [1]. Subsequently, several others have been identified and functional studies on these mutations have been performed using a heterologous expression system [2,7-11]. Despite many studies, the molecular and cellular mechanisms underlying Brugada syndrome are not completely known [12,13].Nav1.5 channels initiate action potentials in most cardiac myocytes and thus play a critical role in cardiac excitability and impulse propagation. Some Brugada syndrome-related SCN5A mutations produce lose-of-function defects by completely disrupting Nav1.5 function [1] or by reducing ion permeation or membrane surface expression [14], whereas others elicit a functional deficit by accelerating the rates of fast and slow inactivation [7,9,14,15]. The identification of the various clinical phenotypes resulting from SCN5A mutations is critical for optimal patient management. In addition, an understanding of the structural-functional relationship of the Nav1.5 channel may result in the development of new therapies for heart diseases.In this study, we describe the functional properties of an Nav1.5 mutation, A551T, identified in a patient with Brudaga syndrome, whose resting ECG showed a coved-type ST elevation in the right precordial leads [16]. We found that the A551T mutation decreased the Na+ current density, enhanced entry into fast ina
%U http://www.jbiomedsci.com/content/16/1/76