Modulation of the late sodium current by ATX‐II and ranolazine affects the reverse use‐dependence and proarrhythmic liability of IKr blockade

• Published in: British journal of pharmacology Vol. 164; no. 2; pp. 308 - 316
• Main Authors: Jia, Shaobin, Lian, Jiangfan, Guo, Donglin, Xue, Xiaolin, Patel, Chinmay, Yang, Lin, Yuan, Zuyi, Ma, Aiqun, Yan, Gan‐Xin
• Format: Journal Article
• Language: English
• Published: Oxford, UK Blackwell Publishing Ltd 01.09.2011; Nature Publishing Group
• Subjects: Acetanilides; Animals; Anti-Arrhythmia Agents - pharmacology; Biological and medical sciences; Clarithromycin - pharmacology; Cnidarian Venoms - pharmacology; Heart Ventricles - drug effects; late sodium current; Medical sciences; Pharmacology. Drug treatments; Piperazines; Potassium Channel Blockers - pharmacology; Potassium Channels, Voltage-Gated - antagonists & inhibitors; Rabbits; Ranolazine; Research Papers; reverse use‐dependence; Sodium Channels; Sotalol - pharmacology; Torsades de Pointes - chemically induced; Torsades de Pointes - physiopathology; Tp‐e; Tp‐e/QT ratio and TdP; Antianginal agent; Late; QT; Coronary vasodilator agent; Ionic current; late sodium current; Ranolazine; reverse use-dependence; Sodium; T; Dependence; QT ratio and TdP; Piperazine derivatives

BACKGROUND AND PURPOSE Drug‐induced torsades de pointes (TdP) often occurs during bradycardia due to reverse use‐dependence. We tested the hypothesis that inhibition or enhancement of late sodium current (INa,L) could modulate the drug‐induced reverse use‐dependence in QT and Tp‐e (an index of dispe...