Bupleurum exerts antiarrhythmic effects by inhibiting L-type calcium channels in mouse ventricular myocytes.

BACKGROUND: Bupleurum (Bup), is a traditional effective medicine to treat colds and fevers in clinics. Multiple studies have demonstrated that Bup exhibites various biological activities, including cardioprotective effects, anti-inflammatory, anticancer, antipyretic, antimicrobial, and antiviral effects, etc. Currently, the effects of Bup on cardiac electrophysiology have not been reported yet. METHODS: Electrocardiogram recordings were used to investigate the effects of Bup on aconitine-induced arrhythmias. Patch-clamp techniques were used to explore the effects of Bup on APs and ion currents. RESULTS: Bup reduced the incidence of ventricular fibrillation (VF) and delayed the onset time of ventricular tachycardia (VT) in mice. Additionally, Bup (40 mg/mL) suppressed DADs induced by high-Ca2+ and shortened action potential duration at 50 % completion of repolarization (APD50) and action potential duration at 90 % completion of repolarization (APD90) to 60.89 % ± 8.40 % and 68.94 % ± 3.24 % of the control, respectively. Moreover, Bup inhibited L-type calcium currents (ICa.L) in a dose-dependent manner, with an IC50 value of 25.36 mg/mL. Furthermore, Bup affected the gated kinetics of L-type calcium channels by slowing down steady-state activation, accelerating the steady-state inactivation, and delaying the inactivation-recovery process. However, Bup had no effects on the Transient sodium current (INa.T), ATX II-increased late sodium current (INa.L), transient outward current (Ito), delayed rectifier potassium current (IK), or inward rectifier potassium current (IK1). CONCLUSION: Bup is an antiarrhythmic agent that may exert its antiarrhythmic effects by inhibiting L-type calcium channels.

Naringin exerts antiarrhythmic effects by inhibiting channel currents in mouse cardiomyocytes.

INTRODUCTION: Naringin, a flavonoid extracted from citrus plants, has a variety of biological effects. Studies have shown that increasing the consumption of flavonoid-rich foods can reduce the incidence of cardiac arrhythmia. Naringin has been reported to have beneficial cardiovascular effects and thus can be used to prevent cardiovascular diseases, but the electrophysiological mechanism through which it prevents arrhythmias has not been elucidated. This study was conducted to investigate the effect of naringin on the transmembrane ion channel currents in mouse ventricular myocytes and the antiarrhythmic effect of this compound on Langendorff-perfused mouse hearts. METHODS: Action potentials (APs) and ionic currents were recorded in isolated ventricular myocytes using the whole-cell patch-clamp technique. Anemone toxin II (ATX II) and CaCl2 were used to induce early afterdepolarizations (EADs) and delayed afterdepolarizations (DADs), respectively. Electrocardiogram (ECG) recordings were conducted in Langendorff-perfused mouse hearts with a BL-420F biological signal acquisition and analysis system. RESULTS: At the cellular level, naringin shortened the action potential duration (APD) of ventricular myocytes and decreased the maximum depolarization velocity (Vmax) of APs.Naringin inhibited the L-type calcium current (ICa.L) and ATX II enhanced the late sodium current (INa.L) in a concentration-dependent manner with IC50 values of 508.5 µmol/L (n = 9) and 311.6 µmol/L (n = 10), respectively. In addition, naringin also inhibited the peak sodium current (INa·P) and delayed the rectifier potassium current (IK) and the transient outward potassium current (Ito). Moreover, naringin reduced ATX II-induced APD prolongation and EADs and had a significant inhibitory effect on CaCl2-induced DADs as well. At the organ level, naringin reduced the incidence of ventricular tachycardia (VT) and ventricular fibrillation (VF) induced by ATX II and shortened the duration of both in isolated hearts. CONCLUSION: Naringin can inhibit the occurrence of EADs and DADs at the cellular level; furthermore, it can inhibit INa.L, ICa.L, INa·P, IK, and Ito in ventricular myocytes. Naringin also inhibits arrhythmias induced by ATX II in hearts. By investigating naringin with this electrophysiological method for the first time, we determined that this flavonoid may be a multichannel blocker with antiarrhythmic effects.

Eleutheroside B, a selective late sodium current inhibitor, suppresses atrial fibrillation induced by sea anemone toxin II in rabbit hearts.

Eleutheroside B (EB) is the main active constituent derived from the Chinese herb Acanthopanax senticosus (AS) that has been reported to possess cardioprotective effects. In this study we investigated the effects of EB on cardiac electrophysiology and its suppression on atrial fibrillation (AF). Whole-cell recording was conducted in isolated rabbit atrial myocytes. The intracellular calcium ([Ca2+]i) concentration was measured using calcium indicator Fura-2/AM fluorescence. Monophasic action potential (MAP) and electrocardiogram (ECG) synchronous recordings were conducted in Langendorff-perfused rabbit hearts using ECG signal sampling and analysis system. We showed that EB dose-dependently inhibited late sodium current (INaL), transient sodium current (INaT), and sea anemone toxin II (ATX II)-increased INaL with IC50 values of 167, 1582, and 181 µM, respectively. On the other hand, EB (800 µM) did not affect L-type calcium current (ICaL), inward rectifier potassium channel current (IK), and action potential duration (APD). Furthermore, EB (300 µM) markedly decreased ATX II-prolonged the APD at 90% repolarization (APD90) and eliminated ATX II-induced early afterdepolarizations (EADs), delayed afterdepolarizations (DADs), and triggered activities (TAs). Moreover, EB (200 µM) significantly suppressed ATX II-induced Na+-dependent [Ca2+]i overload in atrial myocytes. In the Langendorff-perfused rabbit hearts, application of EB (200 µM) or TTX (2 µM) substantially decreased ATX II-induced incidences of atrial fibrillation (AF), ventricular fibrillation (VF), and heart death. These results suggest that augmented INaL alone is sufficient to induce AF, and EB exerts anti-AF actions mainly via blocking INaL, which put forward the basis of pharmacology for new clinical application of EB.

Antiarrhythmic effect of crotonoside by regulating sodium and calcium channels in rabbit ventricular myocytes.

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 (Vmax) 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 (INa) and L-type calcium current (ICaL) in a concentration-dependent manner with half-maximal inhibitory concentrations (IC50) of 192 µmol/L and 159 µmol/L, respectively. However, Cro had no significant effects on the inward rectifier potassium current (IK1) or rapidly activating delayed rectifier potassium current (IKr). Sea anemone toxin II (ATX II) increased the late sodium current (INaL), 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 INa, INaL, and ICaL in ventricular myocytes. Cro has antiarrhythmic potential and thus deserves further study.