Antiarrhythmic effect of crotonoside by regulating sodium and calcium channels in rabbit ventricular myocytes
Life Sciences(2020)
Abstract
Aims: Detect the antiarrhythmic effect of crotonoside (Cro). Main methods: We used whole-cell patch-clamp techniques to detect the effects of Cro on action potentials (APs) and transmembrane ion currents in isolated rabbit left ventricular myocytes. We also verified the effect of Cro on ventricular arrhythmias caused by aconitine in vivo. Key findings: Cro reduced the maximum depolarization velocity (V-max) of APs and shortened the action potential duration (APD) in a concentration-dependent manner, but it had no significant effect on the resting membrane potential (RMP) or action potential amplitude (APA). It also inhibited the peak sodium current (I-Na) and L-type calcium current (I-CaL) in a concentration-dependent manner with half-maximal inhibitory concentrations (IC50) of 192 mu mol/L and 159 mu mol/L, respectively. However, Cro had no significant effects on the inward rectifier potassium current (I-K1) or rapidly activating delayed rectifier potassium current (I-Kr). Sea anemone toxin II (ATX II) increased the late sodium current (I-NaL), but Cro abolished this effect. Moreover, Cro significantly abolished ATX II-induced early afterdepolarizations (EADs) and high extracellular Ca2+ concentration (3.6 mmol/L)-induced delayed afterdepolarizations (DADs). We also verified that Cro effectively delayed the onset time and reduced the incidence of ventricular arrhythmias caused by aconitine in vivo. Significance: These results revealed that Cro effectively inhibits I-Na, I-NaL, and I-CaL in ventricular myocytes. Cro has antiarrhythmic potential and thus deserves further study.
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Key words
Crotonoside,Peak sodium current,Late sodium current,L-type calcium current,Ventricular arrhythmias
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