Icariin,a Blocker Of Sodium And Calcium Channels,Inhibits Arrhythmias In Rabbits

Backgroud Icariin,a flavonoid extracted from Herba Epimedii,has been confirmed to have cardioprotective effects.However,its effects on arrhythmias and cardiac electrophysiology remain unclearAims Thus,in this study,we aimed to investigate the effects of icariin not only on ion currents and action potentials(APs)in the rabbit myocardium,but also on aconitine-induced ventricular arrhythmiasMethods Ion currents and APs were recorded in voltage-clamp and current-clamp mode in rabbit left ventricular myocytes(LVMs)and left atrial myocytes(LAMs),respectivelyResults Icariin significantly shortened action potential durations(APDs)at 50%and 90%repolarization(APD50 and APD90)and reduced the maximum upstroke velocity(Vmax)of APs in a concentration-dependent manner in LAMs and LVMs;however,icariin had no effect on AP amplitude(APA)or resting membrane potential(RMP)in these cells.Icariin decreased the reverse rate dependence(RRD)of the APD and completely abolished anemonia toxin II(ATX-II)-induced early afterdepolarizations(EADs).Moreover,icariin significantly suppressed delayed afterdepolarizations(DADs)and triggered activities(TAs)elicited by isoproterenol(ISO,1 μM)and high extracellular calcium concentrations([Ca2+]o,3.6 mM)in LVMs Icariin also decreased INaT in a concentration-dependent manner in LAMs and LVMs,with IC50 values of 12.28±0.29 μM(n=8)and 11.83±0.92 μM(n=10;p>0.05 versus LAMs),respectively,and reversed ATX-II-induced INaL in a concentration-dependent manner in LVMs.Furthermore,icariin attenuated ICaL in a dose-dependent manner in LVMs.The corresponding IC50 value was 4.78±0.89 μM(n=13),indicating that the above mentioned current in LVMs was 2.8-fold more sensitive to icariin than ICaL in LAMs(13.43±2.73 μM;n=9).Icariin induced leftward shifts in the steady-state inactivation curves of INaT and ICaL in LAMs and LVMs and accelerated their inactivation processes but did not have a significant effect on their activation processes Moreover,icariin had no effects on IK1 and IKr in LVMs or Ito and IKur in LAMs Moreover,Icariin could significantly(P<0.01)increase the onset dosage and onset time of ventricular premature contraction(VPC),ventricular tachycardia(VT)and ventricular fibrillation(VF)induced by aconitine in rabbits,and the survival rate of rabbits was significantly increased(P<0.01)Conclusion These results revealed that icariin is a multichannel blocker that affects INaT,INaL and ICaL in the myocardium and that the drug had significant inhibitory effects on arrhythmias.Therefore,icariin has potential as a class I and IV anti arrhythmic drug.