Wenxin Keli diminishes Ca²⁺overload induced by hypoxia/reoxygenation in cardiomyocytes through inhibiting INaLand ICaL

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.