Curcumin, a Multi-Ion Channel Blocker That Preferentially Blocks Late Na+ Current and Prevents I/R-Induced Arrhythmias

Lv Song; Ze-Fu Zhang; Liang-Kun Hu; Pei-Hua Zhang; Zhen-Zhen Cao; Zhi-Pei Liu; Pei-Pei Zhang; Ji-Hua Ma

doi:10.3389/fphys.2020.00978

Curcumin, a Multi-Ion Channel Blocker That Preferentially Blocks Late Na⁺ Current and Prevents I/R-Induced Arrhythmias

Front Physiol. 2020 Aug 21:11:978. doi: 10.3389/fphys.2020.00978. eCollection 2020.

Authors

Lv Song^{1

2

3}, Ze-Fu Zhang^{1

3}, Liang-Kun Hu⁴, Pei-Hua Zhang^{1

3}, Zhen-Zhen Cao^{1

3}, Zhi-Pei Liu^{1

3}, Pei-Pei Zhang^{1

3}, Ji-Hua Ma^{1

2

3}

Affiliations

¹ Cardio-Electrophysiological Research Laboratory, Medical College of Wuhan University of Science and Technology, Wuhan, China.
² College of Life Science and Health, Wuhan University of Science and Technology, Wuhan, China.
³ Hubei Province Key Laboratory of Occupational Hazard Identification and Control, Medical College of Wuhan University of Science and Technology, Wuhan, China.
⁴ Tianyou Hospital Affiliated to Wuhan University of Science and Technology, Wuhan, China.

Abstract

Increasing evidence shows that Curcumin (Cur) has a protective effect against cardiovascular diseases. However, the role of Cur in the electrophysiology of cardiomyocytes is currently not entirely understood. Therefore, the present study was conducted to investigate the effects of Cur on the action potential and transmembrane ion currents in rabbit ventricular myocytes to explore its antiarrhythmic property. The whole-cell patch clamp was used to record the action potential and ion currents, while the multichannel acquisition and analysis system was used to synchronously record the electrocardiogram and monophasic action potential. The results showed that 30 μmol/L Cur shortened the 50 and 90% repolarization of action potential by 17 and 7%, respectively. In addition, Cur concentration dependently inhibited the Late-sodium current (I _Na.L), Transient-sodium current (I _Na.T), L-type calcium current (I _Ca.L), and Rapidly delayed rectifying potassium current (I _Kr), with IC₅₀ values of 7.53, 398.88, 16.66, and 9.96 μmol/L, respectively. Importantly, the inhibitory effect of Cur on I _Na.L was 52.97-fold higher than that of I _Na.T. Moreover, Cur decreased ATX II-prolonged APD, suppressed the ATX II-induced early afterdepolarization (EAD) and Ca²⁺-induced delayed afterdepolarization (DAD) in ventricular myocytes, and reduced the occurrence and average duration of ventricular tachycardias and ventricular fibrillations induced by ischemia-reperfusion injury. In conclusion, Cur inhibited I _Na.L, I _Na.T, I _Ca.L, and I _Kr; shortened APD; significantly suppressed EAD and DAD-like arrhythmogenic activities at the cellular level; and exhibited antiarrhythmic effect at the organ level. It is first revealed that Cur is a multi-ion channel blocker that preferentially blocks I _Na.L and may have potential antiarrhythmic property.

Keywords: action potential; arrhythmias; curcumin; ionic currents; ischemia–reperfusion; ventricular myocytes.