SCN5A and Nav1.5 Mutations in Regular and Irregular Cardiomyocyte Function and Arrhythmic Conduction Disorders

In the heart, electrical conduction by gap junctions allows for the rapid and synchronous contraction of the heart by the net flux of K+, Ca2+, and Na+ ions1. These ions also enter cells through ion channels to initiate and propagate action potentials; the sodium ion channel is an integral part of this regulated process. Sodium channels are made of essential but varied subunits. For example, the Nav1.5 sodium ion channel, a major voltage gated channel in the heart, has an ?-subunit that is coded for by the SCN5A gene2,3. Mutations to the SCN5A gene and its products result in mutated expression of the ?-subunit and cause variance in channel inactivation speed and function4. This contributes to conditions such as long QT3 (LQT3), Brugada, Romano-Ward, sick sinus, and sudden infant death syndromes, atrial and ventricular fibrillation, dilated cardiomyopathy and other overlapping cardiac conduction abnormalities3,4,5,6. This paper will examine the normal physiological role and expression of SCN5A and Nav1.5, common mutations, associated conditions, and treatments/management.

Overview of the SCN5A Gene, Sodium Channels and Nav1.5

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The SCN5A gene is located on chromosome 3 at location 21; more specifically, it encompasses 101611 base pairs from 38589552 to 38691163, and encodes for the ?-subunit of the Nav1.5 voltage gated sodium ion channel2,3. The SCN5A gene is a part of the SCN family (SCN1A-SCN11A) that encodes for voltage gated sodium channels in skeletal muscle, smooth muscle, cardiac muscle, and the brain (it has also been found in breast cancer cells)2. Again, SCN5A encodes for cardiomyocyte voltage gated sodium channels.Sodium Channels and Nav1.5

Nav1.5 is comprised of two ?-subunits non-covalently linked to an ?-subunit…

…ome. Circulation – Arrhythmia and Electrophysiology, 6, 177-184.

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19. Tuzcu V., Kilinc O.U. (2012). Successful Elimination of Significant Arrhythmia Burden with Flecainide in an Adolescent with Long QT Syndrome Type 3. Congenital Heart Disease, 7(4), E42-E45.


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