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Icariin, a flavonoid monomer from  Herba Epimedii , has confirmed pharmacological and biological effects. However, its effects on arrhythmias and cardiac electrophysiology remain unclear. Here we investigate the effects of icariin on ion currents and action potentials (APs) in the rabbit myocardium. Furthermore, the effects of icariin on aconitine-induced arrhythmias were assessed in whole rabbits. Ion currents and APs were recorded in voltage-clamp and current-clamp mode in rabbit left ventricular myocytes (LVMs) and left atrial myocytes (LAMs), respectively. Icariin significantly shortened action potential durations (APDs) at 50 and 90% repolarization (APD 50  and APD 90 ) and reduced AP amplitude (APA) and the maximum upstroke velocity (V max ) of APs in LAMs and LVMs; however, icariin had no effect on resting membrane potential (RMP) in these cells. Icariin decreased the rate-dependence 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 ([Ca 2+ ] o , 3.6 mM) in LVMs. Icariin also decreased I NaT  in a concentration-dependent manner in LAMs and LVMs, with IC 50  values of 12.28 ± 0.29 μM ( n  = 8 cells/4 rabbits) and 11.83 ± 0.92 μM ( n  = 10 cells/6 rabbits;  p  > 0.05 vs. LAMs), respectively, and reversed ATX-II-induced I NaL  in a concentration-dependent manner in LVMs. Furthermore, icariin attenuated I CaL  in a dose-dependent manner in LVMs. The corresponding IC 50  value was 4.78 ± 0.89 μM ( n  = 8 cells/4 rabbits), indicating that the aforementioned current in LVMs was 2.8-fold more sensitive to icariin than I CaL  in LAMs (13.43 ± 2.73 μM;  n  = 9 cells/5 rabbits). Icariin induced leftward shifts in the steady-state inactivation curves of I NaT  and I CaL  in LAMs and LVMs but did not have a significant effect on their activation processes. Moreover, icariin had no effects on I K1  and I Kr  in LVMs or I to  and I Kur  in LAMs. These results revealed for the first time that icariin is a multichannel blocker that affects I NaT , I NaL  and I CaL  in the myocardium and that the drug had significant inhibitory effects on aconitine-induced arrhythmias in whole rabbits. Therefore, icariin has potential as a class I and IV antiarrhythmic drug.

frontiers in physiology

Icariin, a Novel Blocker of Sodium and Calcium Channels, Eliminates Early and Delayed Afterdepolarizations, As Well As Triggered Activity, in Rabbit Cardiomyocytes