心宝丸对人超级化激活环核苷酸门控阳离子通道4电生理特性的影响  

Effect of Xin Bao pill on electrophysiological properties of human HCN4 channel

作　　者：胡芬 熊吟[2] 张国兵[3] 

机构地区：[1]武汉市东湖医院内五科,湖北武汉430070 [2]武汉市普爱医院老年病科,湖北武汉430030 [3]浙江大学医学院附属第一医院肿瘤科,浙江杭州310003

出　　处：《中国生化药物杂志》2015年第4期70-73,共4页Chinese Journal of Biochemical Pharmaceutics

基　　金：浙江省卫生厅(2011KYA051)

摘　　要：目的探讨心宝丸对人超极化激活环核苷酸门控阳离子通道4(hyperpolarization-activated cyclic nucleotide-gated channel4,HCN4)电生理特性的影响,从基础医学上阐明心宝丸治疗心动过缓的机制。方法将人HCN4的mRNA注射到非洲爪蟾卵母细胞,孵育2~3 d后,采用双电极电压钳技术观察40mg/L心宝丸灌流液对HCN4通道电流的作用特点。结果测试电位-90mV时40mg/L心宝丸灌流液与对照组(无心宝丸的灌流液)相比,HCN4通道峰电流和尾电流有明显变化,半数最大激活电压(V1/2)分别由(-103.61±3.57)m V、(-81.11±4.26)m V变为(-106.42±5.33)m V、(-86.36±7.44)m V,斜率因子(k)分别由(15.15±2.23)m V、(11.78±0.85)m V变为(l7.33±3.58)m V、(12.39±1.51)m V(n=10)。测试电位-90mV时,40mg/L心宝丸灌流液使瞬时电流减少了(0.15±0.24)%,EC50为(30.8±4.8)mg/L(n=8)。测试电位-140mV到-100mV水平上,40mg/L心宝丸灌流液与对照组(无心宝丸的灌流液)相比延长HCN4通道激活时间常数:[(226.73±31.36)ms vs(143.67±21.44)ms;-140mV,n=10,P<0.05]。40mg/L心宝丸灌流液与对照组(无心宝丸的灌流液)相比延长HCN4通道去激活时间常数[(1293.53±95.02)ms vs(647.12±61.35)ms;-140mV,n=10,P<0.05]。结论心宝丸呈浓度依赖性增强HCN4瞬时电流,延长通道激活和去激活过程。Objective To explore the basic medical mechanism of XinBao pill on electrophysiological characteristics of hyperpolarization-activated cyclic nucleotide-gated channel 4 （HCN4）, and illustrate the mechanism of its therapeutical effect on bradycardia.Methods Human HCN4 mRNA was injected into the Xenopus laevis oocytes, after incubated for 2 ~3 days, channel current properties of HCN4 perfused with 40 mg/L XinBao Pill were observed by double electrode voltage clamp technique.Results At-90mV test potential, compared with control group （no XinBao pill）, HCN4 channel peak current and tail current in 40 mg/L XinBao pill group had obvious changes, and V1/2 from （ -103.61 ±3.57）mV to （ -106.42 ±5.33）mV in XinBao pill group, from（ -81.11 ±4.26）mV to（ -86.36 ±7.44）mV in control group.The values of k from （15.15 ±2.23）mV to （17.33 ±3.58） mV in XinBao pill group, from（11.78 ±0.85）mV to（12.39 ±1.51）mV in control group（n=10）.At test potential -90 mV, 40 mg/L XinBao pill perfusion fluid decreased the instantaneous current of（0.15 ±0.24）%, the EC50 was （30.8 ±4.8）mg/L （n=8）.At test potential-140 mV^-100 mV level, 40 mg/L XinBao pill group increased the channel activation time constant compared with control group[（226.73 ±31.36）ms vs（143.67 ± 21.44）ms;-140 mV,n=10,P〈0.05].40 mg/L XinBao pill group increased the channel deactivation time constant compared with control group [（1293.53 ±95.02）ms vs （647.12 ±61.35）ms;-140 mV,n=10,P〈0.05].Conclusion The XinBao pill enhances the instantaneous current of HCN4 in a concentration-dependent manner, and extents channel activation and deactivation processes.

关 键 词：心宝丸 电生理学 HCN4通道 瞬时电流 双电极电压钳 非洲爪蟾卵母细胞 

分 类 号：R965[医药卫生—药理学]