Year-end Sale % OFF 
Abstract
Nav1.5 is the predominant cardiac sodium channel subtype, encoded by the SCN5A gene, which is involved in the initiation and conduction of action potentials throughout the heart. Along its biosynthesis process, Nav1.5 undergoes strict genomic and non-genomic regulatory and quality control steps that allow only newly synthesized channels to reach their final membrane destination and carry out their electrophysiological role. These regulatory pathways are ensured by distinct interacting proteins that accompany the nascent Nav1.5 protein along with different subcellular organelles. Defects on a large number of these pathways have a tremendous impact on Nav1.5 functionality and are thus intimately linked to cardiac arrhythmias. In the present review, we provide current state-of-the-art information on the molecular events that regulate SCN5A/Nav1.5 and the cardiac channelopathies associated with defects in these pathways.
Highlights
We have provided current state-of-the-art information of the molecular events that emanate with the transcription and transcriptional regulation of the
Distinct interacting proteins accompany the nascent Nav 1.5 protein along with different subcellular organelles until it reaches its final membrane destination, accumulating a large number of diverse post-translational modifications, which eventually allows to carry out a fundamental electrophysiological role on the configuration of the cardiac action potential
It is challenging to deeply understand the molecular mechanisms driving the association of single mutations with distinct impaired electrophysiological entities, such as Brugada and LQT syndrome, or in cases of even more complex phenotypical manifestations, such as sick sinus syndrome, atrial fibrillation, and ventricular tachycardia
Summary
SCN5A gene with 80 kb length is located on chromosome 3p21 and consists of 28 exons which encode a protein of 2016 amino acid, the α-subunit of Nav 1.5 channel [4] This protein contains four homologous sites (DI–DIV), each composed of six transmembrane segments organized into two functional modules. Due to localized Nav 1.5 channels into T-tubules and in the focal adhesion complex or costameres that link adjacent myocytes in the myocardium through extracellular matrix interaction [12,13] This process is characterized by the presence of specific proteins that control Nav 1.5 trafficking and anchoring [13]. All four charged S4 segments change their position in the cell membrane with an outward movement, which leads to the opening of the channel pore, conducting to an inward Na+. At the end of its life cycle, Nav 1.5 is degraded by proteasome and autophagic degradation pathways [11]
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
