Whither art thou, SCN10A, and what art thou doing?
نویسنده
چکیده
Since its initial cloning in 1992, SCN5A (Nav1.5) has become known as “the” cardiac sodium channel.1 SCN5A encodes a tetrodotoxin (TTX)-resistant channel that is responsible for the inward sodium current (INa), which initiates the cardiac action potential. Its RNA and protein expression dominate the sodium channel landscape in the ventricle, atrium, and specialized conduction system. Mice heterozygous for a targeted Scn5a deletion (Scn5a / mice) have slowed conduction along with atrial and ventricular arrhythmias, whereas homozygous targeted deletion in mice is embryonic lethal.2 In humans, pharmacological agents that block SCN5A such as flecainide, developed as antiarrhythmics, are proarrhythmic and increase mortality in patients with structural heart disease.3 In addition, SCN5A mutations cause a potpourri of diseases that lead to sudden cardiac death including long-QT syndrome type 3 (LQT3, gain-of-function mutations that slow inactivation and increase late sodium current, INa,L), Brugada syndrome (BRS1, loss of function mutations that decrease peak INa), conduction disease, atrial fibrillation, and dilated cardiomyopathy.4 More recently, changes in SCN5A (expression, splicing, posttranslational modifications including CaMKII phosphorylation) and/or its -subunits that decrease peak INa or increase INa,L have been implicated as potential contributing factors for more common types of sudden death from acquired heart diseases such as heart failure.5–8
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ورودعنوان ژورنال:
- Circulation research
دوره 111 3 شماره
صفحات -
تاریخ انتشار 2012