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 (100 nM) increased the PV spontaneous rates from 2·0 ± 0·1 to 2·9 ± 0·2 Hz (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 10 μM) dose dependently reduced the PV spontaneous rates from 2·5 ± 0·2 to 2·3 ± 0·2 Hz, 1·9 ± 0·2 and 1·5 ± 0·3 Hz (P < 0·05) and decreased the diastolic tension by 40 ± 19%, 87 ± 26% and 113 ± 28%. In the presence of ranolazine (10 μM), ATX-II (100 nM) further increased the AP duration. However, ATX-II neither increased the PV spontaneous rates (1·6 ± 0·1 vs. 1·7 ± 0·2 Hz, n = 7) nor induced PV burst firing or EAD. Moreover, ranolazine (10 μM) 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) .