摘要
目的 研究盐酸关附甲素（GFA）对分离的单个豚鼠心室肌细胞钠电流（ⅠNa）的影响，旨在探讨其抗心律失常机制。方法 用急性酶解法分离获得单个豚鼠心室肌细胞。用标准的全细胞膜片钳技术记录离子通道电流，观察不同浓度的GFA对豚鼠心室肌细胞ⅠNa的影响。结果 在测试电压-20mV的条件下，50、150、500、750μmol／LGFA使ⅠNa峰值电流密度与用药前比较分别降低了24．24％±2．78％、42．84％±1．39％、61．23％±1．34％和100％±0，各浓度用药前后对比差异均有统计学意义，P〈0．05；GFA对ⅠNa半数抑制浓度（IC50）为184．38μmol／L150μmol／LGFA使ⅠNa的电流密度-电压（I-U）曲线上移，但不改变其激活、峰值和反转电位，不影响ⅠNa的稳态激活曲线；150μmol／LGFA使氏。的稳态失活曲线左移，即向更负的方向移动；150μmol／LGFA使ⅠNa的失活后恢复曲线明显右移，明显减慢钠通道失活后恢复过程；150μmol／LGFA抑制ⅠNa呈使用依赖性。结论 GFA在50～750μmol／L范围内对ⅠNa具有浓度依赖性阻滞作用，而且该作用具有使用依赖性；GFA对钠通道激活态无影响；GFA抑制ⅠNa是作用于失活态而发挥作用；GFA减慢钠通道失活后恢复过程。GFA对ⅠNa的阻滞作用为其抗心律失常作用的主要机制。
Objective The effects of guanfubase A （GFA） on sodium channel current （ⅠNa） were evaluated in isolated ventricular myocytes of guinea pigs using patch clamp whole cell recording techniques to investigate the mechanism of antiarrhythmic action of GFA. Methods Single ventricular cell was obtained from healthy guinea pig hearts using enzymatic dissociation technique. The whole cell patch clamp method was used to record the ⅠNa. Results At the test potential of -20mV, GFA （50, 150, 500, 750 μmol/L） produced 24. 24% ± 2. 78%, 42. 84% ± 1.39%, 61.23% ± 1.34% and 100% ± 0, respectively, concentration-dependent reduction of INs comparing with control, with a mean IC50 （50% inhibitory concentration ） value of 184. 38 μmol/L. GFA inhibited sodium channel current in use-dependent manner. 150 μmol/LGFA shifted up the current-voltage relation curve （I-U） and scaled down the peak ⅠNa without producing any significant effects on activation threshold （ -50 mV）, peak current potential （ -20 mV） and the shape of the I-U curve. After the cell exposed to GFA 150 μmol/L, the steady-state activation curve was not significantly affected, while the steady-state inactivation curve shifted to more negative potentials. GFA slowed the rate of recovery from inactivation. Conclusion GFA can inhibits ⅠNa of guinea pigs ventricular myocytes, in a concentration-depondent manner. It may be the major mechanism of its antiarrhythmic action. GFA does not affect the active state of sodium channel, but it affects on the inactivated state of sodium channel. GFA blocks sodium channel current in use-dependent manner.
出处
《中华心律失常学杂志》
2007年第1期47-52,共6页
Chinese Journal of Cardiac Arrhythmias
基金
国家高技术研究发展计划（863计划）资助（2004AA2Z3820）
关键词
关附甲素
膜片钳
离子通道
豚鼠
心室肌细胞
Guanfubase A
Patch clamp
Ion channel
Guinea pig
Ventricular cell
