Effect of cardiac I_(Na-L) on APD accommodation and drug induced arrhythmia

A number of prescription drugs could block rapidly activating delayed rectifier potassium current(IKr) channel and delay the process of cardiac repolarization.IKr blockers exhibit reverse use dependence,which means that drug-induced repolarization prolongation is more prominent during bradycardia and increase the risk of arrhythmogenesis.Cardiac late sodium current(INa-L) is another important current responsible for repolarization.The inactivation of INa-L channel is voltage and time dependent and has very slow inactivation as well as recovery kinetics.So,INa-L contributes to reverse use dependence and enhance the proarrhythmic effect of IKr blockades.INa-L increases during long QT syndrome type 3(LQT3),cardiac hypertrophy,and heart failure,and unmasks the proarrhythmic effect of safer drugs,eg,amiodarone.Ranolazine,an INa-L blocker,could decrease ventricular heterogeneity of repolarization.It is helpful for the patients with enhanced INa-L to attenuate TdP genesis as taking IKr blockade.