Antiarrhythmia Effect Of Crotonoside By Regulating Sodium And Calcium Channels In Rabbit Ventricular Myocytes

Objectives Crotonoside?Cro?is an important extract in croton,and possesses pharmacological activities,but its effect on cardiac electrophysiology have not been reported.Therefore,this study aimed to explore the effects of Crotonoside on cardiac electrophysiology and its mechanisms.Methods We used whole-cell patch clamp technique to study the effects of Crotonoside on action potentials?APs?,transmembrane ion channels and cellular arrhythmias in rabbit ventricular myocytes.In addition,aconitine-induced arrhythmia in vivo was carried out using a biosignal acquisition and analysis system.Results Crotonoside?100?mol/L and 200?mol/L?reduced the maximum depolarization velocity(V_max)of AP and shortened the action potential duration?APD?in a concentration-dependent manner.But Crotonoside?100?mol/L and 200?mol/L?had no significant effect on resting membrane potential?RMP?and action potential amplitude?APA?;Crotonoside?10?mol/L,50?mol/L,100?mol/L and 200?mol/L?inhibited peak sodium current(I_Na.P)and L-type calcium current(I_Ca.L)in a concentration-dependent manner with IC₅₀0 of 192.23?mol/Land158.99?mol/L,respectively;Crotonoside?10?mol/L,100?mol/L and 200?mol/L?also inhibited ATXII-induced enhancement of late sodium current(I_Na.L);however,Crotonoside?100?mol/L and 200?mol/L?had no significant effects on inward rectifier potassium current(I_K1)and rapidly activateddelayed rectifier potassium current(I_Kr);Moreover,crotonosidealso significantly eliminates ATXII-inducedearly afterdepolarizations?EADs?and Ca²⁺-induced delayed afterdepolarizations?DADs?,Crotonoside effectively delayed the onset time and reduced the incidence of aconitine-induced arrhythmia in vivo.Conclusion Crotonoside effectively inhibited I_Na.P,I_Na.L,I_Ca.La.L in ventricular myocytes,cellular arrhythmia and aconitine-induced arrhythmia in vivo.Therefore,Crotonoside is expected to become a novel antiarrhythmic drug.