title: Nav1.8 channels in ganglionated plexi modulate atrial fibrillation inducibility.
abstract: OBJECTIVE
  Emerging evidences indicate that SCN10A/NaV1.8 is associated with cardiac conduction and atrial fibrillation, but the exact role of NaV1.8 in cardiac electrophysiology remains poorly understood. The present study was designed to investigate the effects of blocking NaV1.8 channels in cardiac ganglionated plexi (GP) on modulating cardiac conduction and atrial fibrillation inducibility in the canine model.
  
  
  RESULTS
  Thirteen mongrel dogs were randomly enrolled. Right cervical vagus nerve stimulation (VNS) was applied to determine its effects on the sinus rate, ventricular rate during atrial fibrillation, PR interval, atrial effective refractory period, and the cumulative window of vulnerability. The NaV1.8 blocker A-803467 (1 μmol/0.5 mL per GP, n = 7) or 5% DMSO/95% polyethylene glycol (0.5 mL per GP, n = 6, control) was injected into the anterior right GP and the inferior right GP. The effects of VNS on the sinus rate, ventricular rate, PR interval, atrial effective refractory period, and the cumulative window of vulnerability were significantly eliminated at 10, 35, and 90 min after A-803467 injection. In separate experiments (n = 8), A-803467 blunted the slowing of sinus rate with increasing stimulation voltage of the anterior right GP at 10 min after local injection.
  
  
  CONCLUSIONS
  Blockade of NaV1.8 channels suppresses the effects of VNS on cardiac conduction and atrial fibrillation inducibility, most likely by inhibiting the neural activity of the cardiac GP.
authors.affiliation: Department of Cardiology, Shanghai First People's Hospital, School of Medicine, Shanghai Jiaotong University, NO 100, Haining Road, Hongkou District, Shanghai 200080, China.
authors.forename: Baozhen
authors.initials: B
authors.lastname: Qi
authors.affiliation: Department of Cardiology, Shanghai First People's Hospital, School of Medicine, Shanghai Jiaotong University, NO 100, Haining Road, Hongkou District, Shanghai 200080, China.
authors.forename: Yong
authors.initials: Y
authors.lastname: Wei
authors.affiliation: Department of Cardiology, Shanghai First People's Hospital, School of Medicine, Shanghai Jiaotong University, NO 100, Haining Road, Hongkou District, Shanghai 200080, China.
authors.forename: Songwen
authors.initials: S
authors.lastname: Chen
authors.affiliation: Department of Cardiology, Shanghai First People's Hospital, School of Medicine, Shanghai Jiaotong University, NO 100, Haining Road, Hongkou District, Shanghai 200080, China.
authors.forename: Genqing
authors.initials: G
authors.lastname: Zhou
authors.affiliation: Department of Cardiology, Shanghai First People's Hospital, School of Medicine, Shanghai Jiaotong University, NO 100, Haining Road, Hongkou District, Shanghai 200080, China.
authors.forename: Hongli
authors.initials: H
authors.lastname: Li
authors.affiliation: Department of Cardiology, Shanghai First People's Hospital, School of Medicine, Shanghai Jiaotong University, NO 100, Haining Road, Hongkou District, Shanghai 200080, China.
authors.forename: Juan
authors.initials: J
authors.lastname: Xu
authors.affiliation: Department of Cardiology, Shanghai First People's Hospital, School of Medicine, Shanghai Jiaotong University, NO 100, Haining Road, Hongkou District, Shanghai 200080, China.
authors.forename: Yu
authors.initials: Y
authors.lastname: Ding
authors.affiliation: Department of Cardiology, Shanghai First People's Hospital, School of Medicine, Shanghai Jiaotong University, NO 100, Haining Road, Hongkou District, Shanghai 200080, China.
authors.forename: Xiaofeng
authors.initials: X
authors.lastname: Lu
authors.affiliation: Department of Cardiology, Shanghai First People's Hospital, School of Medicine, Shanghai Jiaotong University, NO 100, Haining Road, Hongkou District, Shanghai 200080, China.
authors.forename: Liqun
authors.initials: L
authors.lastname: Zhao
authors.affiliation: Department of Cardiology, Shanghai First People's Hospital, School of Medicine, Shanghai Jiaotong University, NO 100, Haining Road, Hongkou District, Shanghai 200080, China.
authors.forename: Feng
authors.initials: F
authors.lastname: Zhang
authors.affiliation: Department of Cardiology, Shanghai First People's Hospital, School of Medicine, Shanghai Jiaotong University, NO 100, Haining Road, Hongkou District, Shanghai 200080, China.
authors.forename: Gang
authors.initials: G
authors.lastname: Chen
authors.affiliation: Wolfson Institute for Biomedical Research, University College London, Wing3.1, Cruciform Building, Gower Street, London WC1E 6BT, UK.
authors.forename: Jing
authors.initials: J
authors.lastname: Zhao
authors.affiliation: Department of Cardiology, Shanghai First People's Hospital, School of Medicine, Shanghai Jiaotong University, NO 100, Haining Road, Hongkou District, Shanghai 200080, China shaowen.liu@hotmail.com.
authors.forename: Shaowen
authors.initials: S
authors.lastname: Liu
mesh_terms: D000814:Aniline Compounds / Q000494:pharmacology; D000818:Animals; D001281:Atrial Fibrillation / Q000209:etiology*; D004285:Dogs; D004558:Electric Stimulation; D004562:Electrocardiography / Q000187:drug effects; D005663:Furans / Q000494:pharmacology; D005725:Ganglia, Autonomic / Q000502:physiology*; D006321:Heart / Q000294:innervation*; D008297:Male; D062559:NAV1.8 Voltage-Gated Sodium Channel / Q000502:physiology*; D012032:Refractory Period, Electrophysiological; D014630:Vagus Nerve / Q000502:physiology
chemical_list: C520740:A 803467; D000814:Aniline Compounds; D005663:Furans; D062559:NAV1.8 Voltage-Gated Sodium Channel
keywords: Atrial fibrillation; Ganglionated plexus; SCN10A; Sodium channel; Vagus nerve