盐酸关附甲素对大鼠心室肌细胞膜L型钙通道(J_(Ca-L))的影响  

Effects of Guanfu base A hydrochloride on heart L-type calcium channel of rat ventricular myocytes

作　　者：高鑫[1] 浦介麟[1] 杨艳敏[1] 吴辉[1] 黄爱杰[1] 史世勇[1] 刘静涵[2] 朱俊[1] 

机构地区：[1]中国医学科学院心血管病研究所中国协和医科大学阜外心血管病医院,北京100037 [2]中国药科大学,南京210038

出　　处：《中国新药杂志》2006年第22期1926-1929,共4页Chinese Journal of New Drugs

基　　金：国家863课题(2002AA2Z3102)

摘　　要：目的:研究盐酸关附甲素对正常大鼠心室肌细胞L型钙离子通道(I_(Ca-L))的影响。方法:应用膜片钳全细胞记录法,记录关附甲素对I_(Ca-L)的作用并对通道动力学进行初步评价。结果:关附甲素呈浓度依赖性阻滞I_(Ca-L),在25,125,250和1000μmol·L^(-1)时I_(Ca-L)峰值电流密度(去极化至0mV时)分别减少为用药前的81．76%, 77．54%,76．46%和64．77%(P＜0．05)。关附甲素使I_(Ca-L)的I-V曲线上移,但不改变其激活电位、峰值电位。关附甲素呈轻度使用依赖性阻滞I_(Ca-L),对I_(Ca-L)静息态有阻滞作用。关附甲素对I_(Ca-L)激活曲线无明显影响,但使I_(Ca-L)失活后再激活的恢复时间常数(τ)延长,有作用于I_(Ca-L)的失活态的可能。结论:因为关附甲素产生明显I_(Ca-L)阻滞的浓度远大于临床浓度,其对I_(Ca-L)的阻滞作用可能不是抗心律失常的主要作用机制。关附甲素呈浓度依赖性阻滞I_(Ca-L),其作用于L型钙通道的静息态,也有可能作用于失活态。Objective： To investigate the effects of Guanfu base A（GFA） on L-type calcium current （ICa-L） of rat ventricular myocytes. Methods： The ICa-Lof the isolated ventricular mycotes in rats administering GFA was measured using a whole-cell patch-clamp technique. Results： GFA reduced the peak L-type calcium current in a concentration-dependent manner, accounting by 81.76% , 77.54% , 76.46% and 64.77% when dosing of 25, 125, 250 and 1 000μmol·L^-1, respectively, compared to the pre-dosing state. GFA up-shifted the current-voltage （Ⅰ-Ⅴ） curves without significant alteration of activation voltage and maximal peak current. GFA blocked the ICa-L at the resting stage of the channel in a mild use-dependent manner, and delayed the time constant （τ） of recovery of ICa-L after inactivation of the channel without significant impact on the steady-state activation curve of ICa-L , suggesting the interaction of GFA with the inactive state of the channel as well as the resting state. Conclusion： The inhibition of ICa-L is not associated with the main anti-arrhythmic mechanism of GFA since the inhibition concentration used was significantly higher than the concentration used clinically. Further studies are needed to clarify which state of L-type calcium channel, resting or inactivating state, is modulating the concentration-dependent inhibition of ICa-L.

关 键 词：关附甲素 心肌L型钙通道(ICa-L) 膜片钳 

分 类 号：R965.1[医药卫生—药理学] R972.2[医药卫生—药学]