Wenxin Keli diminishes Ca2+ overload induced by hypoxia/reoxygenation in cardiomyocytes through inhibiting INaL and ICaL. Issue 12 (16th November 2017)

• Record Type: Journal Article
• Authors: Luo, Antao; Liu, Zhipei; Cao, Zhenzhen; Hao, Jie; Wu, Lin; Fu, Chen; Zeng, Mengliu; Jiang, Wanzhen; Zhang, Peihua; Zhao, Buchang; Zhao, Tao; Zhao, Jing; Ma, Jihua
• Is Part Of: Pacing and clinical electrophysiology. Volume 40:Issue 12(2017)
• Page Start: 1412
• Page End: 1425
• Publication Date: 2017-11-16
• Subjects: calcium overload -- cardiomyocyte -- hypoxia‐rexoygenation -- late sodium current -- Wenxin Keli; Cardiac pacing -- Periodicals; Electrophysiology -- Periodicals; 617.4120645
• DOI: 10.1111/pace.13206
• Languages: English
• ISSNs: 0147-8389

Abstract

Abstract: Background: An increase in the late sodium current (INaL ) causes intracellular Na + overload and subsequently intracellular Ca 2+ ([Ca 2+ ]i ) overload via the stimulated reverse Na + ‐Ca 2+ exchange (NCX). Wenxin Keli (WXKL) is an effective antiarrhythmic Chinese herb extract, but the underlying mechanisms are unclear. Methods and results: The INaL, NCX current (INCX ), L‐type Ca 2+ current (ICaL ), and action potentials were recorded using the whole‐cell patch‐clamp technique in rabbit ventricular myocytes. Myocyte [Ca 2+ ]i transients were measured using a dual excitation fluorescence photomultiplier system. WXKL decreased the enhanced INaL, reverse INCX, diastolic [Ca 2+ ]i, and the amplitude of Ca 2+ transients induced by sea anemone toxin II (ATX II, a specific INaL channel opener) in a concentration‐dependent manner. Hypoxia increased INaL, INCX, and diastolic [Ca 2+ ]i, and decreased amplitude of [Ca 2+ ]i transients. Hypoxia‐reoxygenation aggravated these changes and induced spontaneous [Ca 2+ ]i transients and hypercontraction in 86% cells (6/7). The application of WXKL during hypoxia or reoxygenation periods decreased the increased INaL, INCX, and diastolic [Ca 2+ ]i, and prevented those events in 82% cells (9/11) under hypoxia‐reoxygenation conditions. WXKL also inhibited the ICaL in a dose‐dependent manner. Furthermore, WXKL shortened the action potential duration and completely abolished ATX II‐induced early afterdepolarizations from 9/9 to /9. In isolated heart electrocardiogram recordings, WXKL inhibited ischemia‐reperfusion induced ventricular premature beats and tachycardia. Conclusions: WXKL attenuated [Ca 2+ ]i overload induced by hypoxia‐reoxygenation in ventricular myocytes through inhibiting INaL and ICaL and prevents arrhythmias. This could, at least partly, contribute to the antiarrhythmic effects of WXKL.