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Wenxin Keli diminishes Ca 2+ overload induced by hypoxia/reoxygenation in cardiomyocytes through inhibiting I NaL and I CaL
Author(s) -
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
Publication year - 2017
Publication title -
pacing and clinical electrophysiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.686
H-Index - 101
eISSN - 1540-8159
pISSN - 0147-8389
DOI - 10.1111/pace.13206
Subject(s) - medicine , myocyte , hypoxia (environmental) , afterdepolarization , diastole , repolarization , patch clamp , endocrinology , cardiology , pharmacology , electrophysiology , chemistry , oxygen , organic chemistry , blood pressure
Background An increase in the late sodium current (I NaL ) 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 I NaL , NCX current (I NCX ), L‐type Ca 2+ current (I CaL ), 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 I NaL , reverse I NCX , diastolic [Ca 2+ ] i , and the amplitude of Ca 2+ transients induced by sea anemone toxin II (ATX II, a specific I NaL channel opener) in a concentration‐dependent manner. Hypoxia increased I NaL , I NCX , 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 I NaL , I NCX , and diastolic [Ca 2+ ] i , and prevented those events in 82% cells (9/11) under hypoxia‐reoxygenation conditions. WXKL also inhibited the I CaL 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 I NaL and I CaL and prevents arrhythmias. This could, at least partly, contribute to the antiarrhythmic effects of WXKL.