The Protective Effects Of Andrographolide Against Arrhythmias Via Inhibting Sodium And Calcium Channel

Andrographolide?Andro?has significant protective effect on cardiovascular system.However,its effects in vivo and its effects on ion channels and action potential?AP?in cardiomyocytes remains unknown.This study aims to explore the effects of Andro on AP and ion channels including I_Na,I_CaL,I_K1,I_Kr,I_to and I_Kur in rabbit cardiomyocytes via whole-cell patch clamp and current clamp techniques.The effects of andrographolide on aconitine-induced arrhythmias was recored using the ECG recording method.In cellular experiments: Andro?5?M and 10?M?shortened action potential duration at 50% repolarization(APD₅₀),at 90% repolarization(APD₉₀)and maximum upstroke velocity(V_max)without having significant effect on resting membrane potential?RMP?and action potential amplitude?APA?in rabbit left ventricular myocytes?LVMs?and left atrial myocytes?LAMs?.Andro attenuated rate-dependent?RD?of action potential duration?APD?,markedly reduced or abolished delayed afterdepolarizations?DADs?and triggered activities?TAs?induced by isoproterenol?ISO,1 ?M?and high calcium([Ca²⁺]o=3.6 m M)in LVMs.Meanwhile,it inhibited I_Na concentration-dependently with an IC₅₀ of 8.28±1.26 ?M and 10.41±3.18 ?M in LVMs and LAMs respectively,and inhibited I_CaL in a concentration dependent manner with an IC₅₀ of 10.08±1.15 ?M and 11.91±1.55 ?M in LVMs and LAMs respectively.Andro?40 ?M?had no significant effect on the I_to and I_Kur in LAMs as well as the I_K1 and I_Kr in LVMs.In vivo experiments: Andrographolide prolonged the onset time and increased the onset dosage of aconitine-induced arrhythmias.What is more,it reduced the incidence of aconitine-induced ventricular arrhythmias and the mortality of rabbits.These results first indicate that andrographolide has obvious inhibitory effects on I_Na,I_CaL,cellular arrhythmias?delayed afterdepolarizations and triggered activities?and aconitine-induced ventricular arrhythmias?ventricular premature contraction,ventricular tachycardia and ventricular fibrillation?.Ultimately,Andro may be used as a class I and IVantiarrhythmia drugs.