利多卡因对心室肌细胞快钠电流的使用依赖性阻滞及其电压依赖性研究  

Use-dependent block of transient sodium current and its voltage-dependence by lidocaine in ventricular myocytes

作　　者：杨震 郭维娜 张玮[2] 马欣[2] 马全萍 戴亚东 于欣[2] YANG Zhen;GUO Wei-na;ZHANG Wei;MA Xin;MA Quan-ping;DAI Ya-dong;YU Xin(Heart Center,The General Hospital of Ningxia Medical University,Yinchuan 750004,Ningxia Hui Autonomous Region,China;Department of Laboratory Medicine,The Clinic College,Ningxia Medical University,Yinchuan 750004,Ningxia Hui Autonomous Region,China)

机构地区：[1]宁夏医科大学总医院心脏中心,宁夏回族自治区银川750004 [2]宁夏医科大学临床学院检验系,宁夏回族自治区银川750004

出　　处：《中国临床药理学杂志》2020年第7期809-812,共4页The Chinese Journal of Clinical Pharmacology

基　　金：国家自然科学基金资助项目(81660056);宁夏高等学校优秀青年教师培育基金项目(NGY2018-98);宁夏留学人员科技活动择优资助项目[宁人社函(2016)494号]。

摘　　要：目的研究利多卡因对兔心室肌细胞快钠电流(INa-T)的Ⅰ-Ⅴ曲线及失活的作用,以及对INa-T的使用依赖性阻滞及其电压依赖性。方法用酶消化法急性分离成年新西兰大白兔的心室肌细胞,用膜片钳技术检测100μmol·L-1利多卡因干预前后心室肌细胞的INa-TⅠ-Ⅴ曲线和失活,以及利多卡因对INa-T的使用依赖性阻滞及其电压依赖性。结果利多卡因阻滞了INa-T,Ⅰ-Ⅴ曲线明显上移,峰值电流显著下降[(2468±389)pA vs(3223±367)pA,P<0.05)],增强了INa-T的失活,失活曲线左移,半失活电压负值增大[(-77±8)mV vs(-55±7)mV,P<0.05]。当以5 Hz频率刺激时,干预前末次刺激与首次刺激诱发的INa-T,差异无统计学意义[(3145±323)pA vs(3287±432)pA,P>0.05]。而利多卡因灌流后,INa-T明显抑制[(1125±298)pA vs(2365±376)pA,P<0.05]。分别以-100,-90和-80 mV的钳制电位检测利多卡因对INa-T的使用依赖性阻滞,阻滞分数分别为(0.31±0.12)和(0.46±0.10)和(0.55±0.08),-100 mV组的阻滞分数与-90和-80 mV组比较,差异均有统计学意义(均P<0.05)。结论利多卡因使INa-T的Ⅰ-Ⅴ曲线上移,促进INa-T的失活,对INa-T的阻滞作用呈使用依赖性,并具有明显的电压依赖性。Objective To study the effects of lidocaine on Ⅰ-Ⅴ curve, inactivation and use-dependent block of transient sodium current(INa-T) as well as its voltage-dependence.Methods Hearts of New Zealand white rabbits were acutely cut off and digested using enzyme solution, and individual ventricular myocytes were isolated.The microelectrode and patch clamp techniques were used to record INa-T before and after perfusion of lidocaine(100 μmol·L-1).Ⅰ-Ⅴ curve, inactivation curve, use-dependent block as well as its voltage-dependence were detected, obtained and analyzed.Results After the perfusion of 100 μmol·L-1 lidocaine, the Ⅰ-Ⅴ curve of INa-T was significantly shifted upward with peak current decreased significantly[(2468±389) pA vs(3223±367) pA,P<0.05)], inactivation curve of INa-T shifted leftward with more negative half inactivation potential [(-77±8)mV vs(-55±7)mV, P<0.05].Under the stimulation at 5 Hz, there was no statistically significant difference in INa-T between 1st pulse and 40th pulse [(3145±323)pA vs(3287±432)pA,P>0.05] before the perfusion of 100 μmol·L-1 lidocaine,while after lidocaine perfusion,the IN a-T of 40 th pulse was significantly decreased compared with that of the 1 st pulse [(1125±298) pA vs(2365±376) pA,P < 0.05].Under different holding potentials of -100 mV,-90 mV and-80 mV,there were statistically significant differences in IN a-T inhibition fractions of use-dependent block produced by lidocaine,with(0.31±0.12) at -100 mV,(0.46±0.10) at-90 mV and(0.55±0.08) at -80 mV.Conclusion Lidocaine shifted upward the Ⅰ-Ⅴ curve of IN a-T,enhanced inactivation of INa-T and blocked the IN a-T use-dependently with voltage-dependence.

关 键 词：利多卡因 快钠电流 失活 使用依赖性阻滞 电压依赖性 

分 类 号：R972.2[医药卫生—药品]