Wenxin Keli diminishes Ca 2+ overload induced by hypoxia/reoxygenation in cardiomyocytes through inhibiting I NaL and I CaL .

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.
(© 2017 Wiley Periodicals, Inc.)