a-803467 and Atrial-Fibrillation

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.. 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.. 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.

Topics: Aniline Compounds; Animals; Atrial Fibrillation; Dogs; Electric Stimulation; Electrocardiography; Furans; Ganglia, Autonomic; Heart; Male; NAV1.8 Voltage-Gated Sodium Channel; Refractory Period, Electrophysiological; Vagus Nerve