Effects Of Curcumin On Ion Channels Of Rabbit Ventricular Myocytes And Its Antiarrhythmic Effect

Aims:The present study was to investigate the effects of Curcumin?Cur?on the action potential and transmembrane ionic currents in rabbit ventricular myocytes and explore its antiarrhythmic property.Methods:The effect of Cur on action potential?AP?and transmembrane ion currents were observed by whole-cell patch-clamp technology on acutely isolated single rabbit ventricular myocyte.A multi-channel information acquisition and analysis system was used to simultaneously record the electrocardiogram and single-phase action potentials on isolated rabbit hearts perfused by Langendorff to observe the effect of curcumin on arrhythmia induced by ischemia-reperfusion.Results:In the presence of 30?mol/L Cur,the 50%and 90%repolarization of action potential(APD₅₀,APD₉₀)were shortened by17%and 7%,respectively,without affecting the AP amplitude?APA?,maximum depolarization velocity?Vmax?or resting membrane potential?RMP?.Cur inhibit the Late-sodium current(I_Na.L),Transient-sodium current(I_Na.T),L-type calcium current(I_Ca.L)and Rapidly activation delayed rectifying potassium current(I_Kr)in a concentration-dependent manner,with the IC₅₀0 value was 7.53?mol/L,398.88?mol/L,16.66?mol/L and 9.96?mol/L,respectively.The inhibitory effect of Cur on I_Na.L was 52-fold higher than that of I_Na.T.Cur shifted the steady-state inactivation curve of I_Ca.L to the left and shifted the time-dependent recovery curve to the right.Moreover,Cur decreased the Sea anemone toxin II?ATX??-prolonged APD and suppressed the ATX?-induced early afterdepolarization?EAD?and Ca²⁺-induced delayed afterdepolarization?DAD?in ventricular myocytes,reduced the occurrence and average duration of ischemia-reperfusion?I/R?injury induced ventricular tachycardias and ventricular fibrillations.Conclusion:Cur inhibited I_Na.L,I_Na.T,I_Ca.La.L and I_Kr,shortened the APD,significant suppressed EAD and DAD-Like arrhythmogenic activities at the cellular level and exhibited antiarrhythmic effect at the organ level,which revealed for the first time that Cur is a multi-ion channel blocker that preferentially blocks I_Na.L and may have potential antiarrhythmic property.