Neuronal Nav1.8 Channels as a Novel Therapeutic Target of Acute Atrial Fibrillation Prevention

Background Ganglionated plexus have been developed as additional ablation targets to improve the outcome of atrial fibrillation (AF) besides pulmonary vein isolation. Recent studies implicated an intimate relationship between neuronal sodium channel Nav1.8 (encoded by SCN10A) and AF. The underlying...

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Bibliographic Details
Published in:Journal of the American Heart Association 2016-11, Vol.5 (11), p.n/a
Main Authors: Chen, XiaoMeng, Yu, LiLei, Shi, ShaoBo, Jiang, Hong, Huang, CongXin, Desai, Mayurika, Li, YiGang, Barajas‐Martinez, Hector, Hu, Dan
Format: Article
Language:English
Subjects:
Acute Disease
Aniline Compounds - pharmacology
Animals
atrial fibrillation
Atrial Fibrillation - metabolism
Atrial Fibrillation - therapy
Dogs
electrophysiology
Furans - pharmacology
ganglionated plexus
Heart - drug effects
Heart - innervation
Immunohistochemistry
NAV1.5 Voltage-Gated Sodium Channel - genetics
Nav1.8
NAV1.8 Voltage-Gated Sodium Channel - genetics
NAV1.8 Voltage-Gated Sodium Channel - metabolism
Neurons - metabolism
Original Research
Patch-Clamp Techniques
SCN10A
Time Factors
Voltage-Gated Sodium Channel beta-3 Subunit - genetics
Voltage-Gated Sodium Channel Blockers - pharmacology
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Summary:Background Ganglionated plexus have been developed as additional ablation targets to improve the outcome of atrial fibrillation (AF) besides pulmonary vein isolation. Recent studies implicated an intimate relationship between neuronal sodium channel Nav1.8 (encoded by SCN10A) and AF. The underlying mechanism between Nav1.8 and AF remains unclear. This study aimed to determine the role of Nav1.8 in cardiac electrophysiology in an acute AF model and explore possible therapeutic targets. Methods and Results Immunohistochemical study was used on canine cardiac ganglionated plexus. Both Nav1.5 and Nav1.8 were expressed in ganglionated plexus with canonical neuronal markers. Sixteen canines were randomly administered either saline or the Nav1.8 blocker A‐803467. Electrophysiological study was compared between the 2 groups before and after 6‐hour rapid atrial pacing. Compared with the control group, administration of A‐803467 decreased the incidence of AF (87.5% versus 25.0%, P
ISSN:2047-9980
2047-9980
DOI:10.1161/JAHA.116.004050