ATX-II-induced pulmonary vein arrhythmogenesis related to atrial fibrillation and long QT syndrome

Background Long QT syndrome (LQTS) is associated with a high incidence of atrial fibrillation (AF), but the underlying mechanisms are unclear. Pulmonary veins (PVs) play a critical role in AF genesis. Type 3 LQTS increases late sodium current (I_Na,L), which may increase PV arrhythmogenesis and AF. Therefore, this study examines PV arrhythmogenesis in anemonia sulcata toxin II (ATX-II)-induced type 3 LQTS and evaluates whether the I_Na,L inhibitor ranolazine can suppress PV arrhythmogenesis. Materials and methods Conventional microelectrodes were used to record the action potentials (AP) and contractility in isolated rabbit PV specimens before and after ATX-II administration with or without ranolazine. Results Anemonia sulcata toxin II (100nM) increased the PV spontaneous rates from 2·0±0·1 to 2·9±0·2Hz (n=7), induced PV burst firing (100%) with the genesis of early afterdepolarization (EAD) (86%) and prolonged the AP duration. Ranolazine (0·1, 1 and 10μM) dose dependently reduced the PV spontaneous rates from 2·5±0·2 to 2·3±0·2Hz, 1·9±0·2 and 1·5±0·3Hz (P<0·05) and decreased the diastolic tension by 40±19%, 87±26% and 113±28%. In the presence of ranolazine (10μM), ATX-II (100nM) further increased the AP duration. However, ATX-II neither increased the PV spontaneous rates (1·6±0·1 vs. 1·7±0·2Hz, n=7) nor induced PV burst firing or EAD. Moreover, ranolazine (10μM) reduced ATX-II-induced PV acceleration and EAD. Conclusions The I_Na,L enhancer ATX-II can increase PV arrhythmogenesis, which can be attenuated or blocked by ranolazine. This suggests that AF may be related to type 3 LQTS through increased I_Na,L.