目的研究犬肺静脉肌袖(PVs)CaV1.2和ERG的mRNA水平,初步探讨其表达与PVs独特离子流特点的关系。方法8只健康犬左上PVs和左房游离壁心肌组织,用逆转录聚合酶链反应法分析CaV1.2和ERG的mRNA在不同部位的表达差别。结果PVs内CaV1.2的mRNA...目的研究犬肺静脉肌袖(PVs)CaV1.2和ERG的mRNA水平,初步探讨其表达与PVs独特离子流特点的关系。方法8只健康犬左上PVs和左房游离壁心肌组织,用逆转录聚合酶链反应法分析CaV1.2和ERG的mRNA在不同部位的表达差别。结果PVs内CaV1.2的mRNA水平较左房降低(1.16±0.07 vs 1.32±0.05,P<0.05),而ERG的mRNA水平较左房有显著的升高(0.87±0.08 vs 0.55±0.09,P<0.05)。结论PVs心肌细胞和左房心肌细胞的CaV1.2和ERG的mRNA表达有差异,此可能导致其离子流特点的不同。展开更多
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...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.展开更多
文摘目的研究犬肺静脉肌袖(PVs)CaV1.2和ERG的mRNA水平,初步探讨其表达与PVs独特离子流特点的关系。方法8只健康犬左上PVs和左房游离壁心肌组织,用逆转录聚合酶链反应法分析CaV1.2和ERG的mRNA在不同部位的表达差别。结果PVs内CaV1.2的mRNA水平较左房降低(1.16±0.07 vs 1.32±0.05,P<0.05),而ERG的mRNA水平较左房有显著的升高(0.87±0.08 vs 0.55±0.09,P<0.05)。结论PVs心肌细胞和左房心肌细胞的CaV1.2和ERG的mRNA表达有差异,此可能导致其离子流特点的不同。
基金Supported by the National Natural Science Foundation of Guangdong(No.2020A1515010777)。
文摘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.