Tertiapin, a selective IK ACh blocker, terminates atrial fibrillation with selective atrial effective refractory period prolongation

Abstract

It is well known that vagal nerve tone plays a crucial role in atrial fibrillation (AF). Acetylcholine-activated potassium current (IK ACh) mediates much of the cardiac response to vagal nerve stimulation (VNS), but the contribution of IK ACh to AF remains unknown. We investigated the role of the IK ACh channel in canine AF models using tertiapin, a selective IK ACh blocker. Tertiapin (4–41 nmol kg −1, i.v.) terminated AF in the canine VNS-induced and aconitine-induced AF models. The muscarinic M-receptor antagonist AF-DX-116 terminated AF in these models, but the adenosine receptor antagonist DPCPX had no effect. Thus it is likely that IK ACh activation via the M-receptor has a crucial role in both models. Tertiapin (12 nmol kg −1, i.v.) preferentially prolonged the atrial effective refractory period (ERP) but not the ventricular ERP under the VNS condition. This peptide (4–41 nmol kg −1, i.v.) did not affect PQ, QRS and corrected QT intervals in isoflurane-anaesthetised dogs. These results suggest that a selective IK ACh blocker is effective in canine AF models without affecting ventricular repolarisation, and might be useful for the treatment of patients with AF.