环维黄杨星D延长大鼠心室肌细胞APD作用的分子机制研究

环维黄杨星D延长大鼠心室肌细胞APD作用的分子机制研究

陈庆文, 单宏丽, 王赫, 李哲, 杨宝峰^*

哈尔滨医科大学药理学教研室, 哈尔滨 150086

收稿日期:2003-04-15 修回日期:2003-08-10 出版日期:2003-09-15 发布日期:2003-09-15
通讯作者: 杨宝峰*

Mechanisms of Cyclovirobuxine D on APD Prolongation in Rat Ventricular Myocytes

CHEN Qing-wen, SHAN Hong-li, WANG He, LI Zhe, YANG Bao-feng^*

Department of Pharmacology, Harbin Medical University, Harbin 150086, China

Received:2003-04-15 Revised:2003-08-10 Online:2003-09-15 Published:2003-09-15
Contact: YANG Bao-feng*

摘要/Abstract

摘要： 目的研究环维黄杨星D对分离的大鼠心室肌细胞内向整流钾电流(IK1)、瞬时外向钾电流(Ito)、L-型钙电流(ICa-L)和动作电位时程(APD)的影响.方法采用全细胞膜片钳技术记录大鼠心室肌细胞IK1、Ito、ICa-L和APD. 结果 1和10 μmol·L^{- 1}环维黄杨星D明显延长分离大鼠心室肌细胞APD50和APD90,10 μmol·L^{- 1}可明显降低静息膜电位(RP).环维黄杨星D对IK1内向电流和外向电流均有明显抑制作用,当指令电压为-100mV时, 1和10 μmol·L^{- 1}环维黄杨星D分别使IK1电流密度从给药前的(-8.0±1.1)pA/pF降至(-4.1±0.7)pA/pF和(-3.4±0.8)pA/pF; 当指令电压-30 mV时, 分别使IK1电流密度从(1.10±0.24)pA/pF降至(0.61±0.18)pA/pF和(0.36±0.11)pA/pF; 在钳制电位从0到+60mV之间, 环维黄杨星D明显抑制Ito, 当指令电压40mV时,1和10 μmol·L^{- 1}环维黄杨星D分别使Ito电流密度从给药前的(8.9±2.0)pA/pF降至(5.5±1.2)pA/pF和(4.9±0.9)pA/pF. 环维黄杨星D浓度依赖性抑制ICa-L, 在指令电压为10 mV时, 1和10 μmol·L^{- 1}分别使ICa-L电流密度从给药前的(-9.9±1.8)pA/pF降至(-6.4±1.4)pA/pF和(-4.2±0.6)pA/pF. 结论环维黄杨星D明显延长大鼠心室肌细胞APD, 抑制IK1、It.和ICa-L,对IK1和Ito的抑制作用是其延长大鼠APD的主要分子机制.

关键词: 环维黄杨星D, 心肌细胞, 离子通道, 动作电位时程, 钾通道, L-型钙电流

Abstract: Aim To study the effects of cyclovirobuxine D on inward rectifier K⁺ current (IK1), transient outward K⁺ current (Ito), L-type Ca²⁺ current (ICa-L), and action potential duration (APD) in isolated rat ventricular myocytes.Methods The whole cell patch-clamp techniques were used to study the changes of IK1, Ito, ICa-L and APD in rat ventricular myocytes. Results Cyclovirobuxine D (1-10 μmol·L^-1) significantly prolonged APD50 and APD90 in isolated rat ventricular myocytes. Resting potential (RP) was decreased by 10 μmol·L^-1 of cyclovirobuxine D. Cyclovirobuxine D significantly decreased both inward and outward components of IK1. At - 100 mV, 1 and 10 μmol·L^-1 of cyclovirobuxine D decreased IK1 density from (-8.0±1.1) pA/pF to (-4.1±0.7) pA/pF and (-3.4±0.8) pA/pF, respectively,whereas at - 30 mV, IK1 density was decreased from (1.10±0.24) pA/pF to (0.61±0.18) pA/pF and (0.36±0.11)pA/pF, respectively. IIto was markedly inhibited by cyclovirobuxine D from the test potential of 0 mV to + 60 mV. At + 40 mV, 1 and 10 μmol·L^-1 of cyclovirobuxine D decreased Ito density from (8.9±2.0) pA/pF to (5.5±1.2) pA/pF and (4.9 + 0.9) pA/pF, respectively. Cyclovirobuxine D inhibited ICa-L in a concentration-dependent manner. At 10 mV, 1 and 10 μmol·L^-1 of cyclovirobuxine D decreased ICa-L density from (-9.9±1.8) pA/pF to (-6.4±1.4) pA/pF and (-4.2±0.6) pA/pF, respectively. Conclusion Cyclovirobuxine D significantly prolonged APD and inhibited IK1, Ito and ICa-L in rat ventricular myocytes. The inhibitory effects of cyclovirobuxine D on IK1 and Ito are major molecular mechanisms of APD prolongation in rat.

Key words: cyclovirobuxine D, cyclovirobuxine D, cardiomyocytes, cardiomyocytes, ion channels, ion channels, APD, APD, potassium channels, potassium channels, L-type ca2+ current, L-type ca2+ current

中图分类号:

R285

R331.3⁺8

Supporting: ^*Corresponding author. Tel.: 0451-86671354; fax: 0451-86669576

陈庆文, 单宏丽, 王赫, 李哲, 杨宝峰^*. 环维黄杨星D延长大鼠心室肌细胞APD作用的分子机制研究[J]. .

CHEN Qing-wen, SHAN Hong-li, WANG He, LI Zhe, YANG Bao-feng^*. Mechanisms of Cyclovirobuxine D on APD Prolongation in Rat Ventricular Myocytes[J]. .

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