Effect of mallotoxin against LQT2 induced by E-4031 in isolated guinea pig hearts and cardiomyocytes / 中国药理学通报

ABSTRACT

Aim To investigate the effect of mallotoxin (MTX) on LQT2 induced by E-4031 in isolated guinea pig hearts and ventricular myocytes.Methods The isolated guinea pig heart underwent retrograde perfusion using Langendorff technique.In order to determine the effects of different concentrations of MTX on QT/QTc interval,transmural dispersion of repolarization (TDR) and index of cardiac electrophysiological balance (iCEB) in the absence and presence of hERG channel blocker E-4031,the electrocardiogram of isolated guinea pig hearts was recorded using Biopac physiological record.Single ventricular myocytes were isolated from guinea pig heart by enzymatic dissociation.Effects of MTX on action potential duration (APD) in the absence and presence of E-4031 were recorded by current clamp mode using whole patch clamp technique.Results MTX shortened the QT interval,reduced TDR,and decreased iCEB in isolated guinea pig heart.MTX could reverse the prolongation of QT interval and the increased TDR induced by E4031.MTX shortened the action potential duration and decreased APDgo,APD60 and APD30 in isolated guinea pig ventricular myocytes.MTX could reverse the prolongation of action potential repolarization duration induced by E-4031.Conclusion MTX shortens QT interval,decreases TDR,reduces iCEB,as well as shortens APD,thus reversing LQT2 induced by E4031.