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 (INa,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 INa,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 (PNa,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 INa,L.
ASJC Scopus subject areas
- Clinical Biochemistry