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

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 Latesodium 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 IC 50 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 Ca 2+-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.

Mechanism-based targeting of cardiac arrhythmias by phytochemicals and medicinal herbs: A comprehensive review of preclinical and clinical evidence

“…Curcumin, a flavonoid found in Curcuma longa L rhizomes, has shown to have a wide range of cardioprotective effects ( 25 ). Song et al ( 26 ) evaluated the antiarrhythmic effects of curcumin (30 mM) and indicated its ability to reduce the incidence and duration of I/R-induced ventricular tachyarrhythmias (VT) and ventricular fibrillation (VF) in Langendorff-perfused rabbit hearts. In in vitro analysis, curcumin reduced the AP duration and suppressed early afterdepolarization (EAD) and Ca 2+ -induced DADs through inhibiting multiple ion channel currents, specifically late Na + channel current ( I Na–L ) and, to some extent, voltage-gated L-type Ca 2+ current ( I Ca–L ) and transient Na + current ( I Na–T ).…”

“…We discussed the antiarrhythmic effects of some active ingredients, including liriodenine, curcumin, cinnamophilin, and resveratrol, through inhibiting Nav channels in previous subsections. Studies have shown that these phytochemicals also behave like class III AADs, as they can modulate the K + channel currents and affect AP duration, thereby protecting the heart against I/R-induced arrhythmias ( 24 , 26 , 29 , 32 , 33 , 36 ). Note that the inhibition of Ca 2+ channels by curcumin, cinnamophilin, and resveratrol might alleviate the prolonged AP duration exerted by inhibiting K + channels.…”

“…We discussed in previous subsections that some phytochemicals, including curcumin, cinnamophilin, barbaloin, and resveratrol, exert their antiarrhythmic effects through modulating multiple ion channels. One of the mechanisms behind their beneficial effects involves blocking the I Ca–L , similar to the action of class IV AADs ( 26 , 27 , 29 , 30 , 32 , 33 , 36 ). As mentioned above, inhibiting I Ca–L in such agents with multiple actions can moderate the AP prolongation that occurs by concurrent inhibition of K + and Na + channels, which could be considered as a starting point for developing future AADs without serious side effects like QT prolongation.…”

Effect of Shenfu Injection on Differentiation of Bone Marrow Mesenchymal Stem Cells into Pacemaker-Like Cells and Improvement of Pacing Function of Sinoatrial Node

“…The currents of the HCN4 channel were measured utilizing the whole-cell patch-clamp approach in a manner that has been previously described [ 27 , 28 ]. BMSCs were detached using trypsin and subcultured onto glass coverslips for a minimum of 30 minutes prior to patch clamping.…”

Hydroxysafflor Yellow A Ameliorates Myocardial Ischemia/Reperfusion Injury by Suppressing Calcium Overload and Apoptosis

“…Patch-Clamp Techniques. Calcium currents were recorded using whole-cell voltage-clamp techniques, as previously reported [23,24]. Currents were digitized at a sampling rate of 5 kHz.…”