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

Yen Yu Lu, Chen Chuan Cheng, Yao Chang Chen, Shih Ann Chen, Yi Jen Chen

Research output: Contribution to journalArticlepeer-review

15 Citations (Scopus)


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 (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 INa,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.

Original languageEnglish
Pages (from-to)823-831
Number of pages9
JournalEuropean Journal of Clinical Investigation
Issue number8
Publication statusPublished - Aug 2012


  • ATX-II
  • Atrial fibrillation
  • Pulmonary veins
  • Type 3 long QT syndrome

ASJC Scopus subject areas

  • Biochemistry
  • Clinical Biochemistry


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