Suxiao Jiuxin Pills Prevent Ventricular Fibrillation from Inhibiting L-type Calcium Currents CaV1.2 in vivo and in vitro

Objective: To investigate whether Suxiao Jiuxin Pills(SJP), a Chinese herbal remedy, is an anti-ventricular fibrillation(VF) agent. Methods: VF was induced by isoproterenolol(ISO) intraperitoneal injection followed by electrical pacing in mice and rabbits. The effects of SJP on the L-type calcium channel current(CaV1.2), voltage-dependent sodium channel current(INa), rapid and slow delayed rectifier potassium channel current(IKr and IKs, respectively) were studied by whole-cell patch-clamp method. Computer simulation was implemented to incorporate the experimental data of SJP effects on the CaV1.2 current into the action potential(AP) and pseudo-electrocardiography(pseudo-ECG) models. Results: SJP prevented VF induction and reduced VF durations significantly in mice and rabbits. Patch-clamp experiments revealed that SJP decreased the peak amplitude of the CaV1.2 current with a half maximal concentration(IC50) value of 16.9 mg/L(SJP-30 mg/L, –32.8±6.1 pA;Verapamil, –16.2±1.8 pA;vs. control, –234.5±16.7 pA, P<0.01, respectively).The steady-state activation curve, inactivation curve, and the recovery from inactivation of the CaV1.2 current were not shifted significantly. Specifically, SJP did not altered INa, IKr, and IKs currents significantly(SJP vs.control, P>0.05). Computer simulation showed that SJP-reduced CaV1.2 current shortened the AP duration,transiting VF into sinus rhythm in pseudo-ECG. Conclusion: SJP reduced VF via inhibiting the CaV1.2 current with in vivo, in vitro, and in silico studies, which provide experimental basis for SJP anti-VF clinical application.