氟卡胺与心肌钠通道相互作用的模拟分析

氟卡胺与心肌钠通道相互作用的模拟分析

吴跃进

广东医学院药理教研室, 湛江 524023

收稿日期:1992-08-11 修回日期:1993-11-10 出版日期:1994-06-15 发布日期:1994-06-15

Modelling and Analysis of Interactions of Flecainid with Cardiac Sodium Channels

Yue-Jin Wu

ment of Pharmacology, Guangdong Medical College, Zhanjiang 524023

Received:1992-08-11 Revised:1993-11-10 Online:1994-06-15 Published:1994-06-15

摘要/Abstract

摘要： 根据闸门相关受体假说, 应用计算机模拟分析了氟卡胺与心肌钠通道相互作用的动力学特点及其作用的闸门相关受体。模型预测的氟卡胺(1 μmol/L)在刺激频率0.1, 0.5, 1.2.0和3.3 Hz时的表观阻滞起效速率分别为0.586, 0.128, 0.071, 0.042和0.030 AP-1, 静息阻滞恢复时间常数为17.4 S, 这些均与文献报道的实验数据一致。对氟卡胺阻滞作用门控过程依赖性的分析表明其依赖于激活门控过程, 氟卡胺1 μmol/L对失活曲线无影响, 但使激活曲线峰值降低, 提示其作用于激活门相关受体, 并可被激活门所滞留, 其与受体结合与解离均受激活过程调控。

关键词: 氟卡胺, 钠通道, 抗心律失常药, 计算机模拟, 闸门相关受体

Abstract: Based on the gate-related receptor hypothesis, modelling and analysis of interactions of flecainide with cardiac sodium channels and the gate-related receptor were performed by computer simulation. Model-predicted apparent rates of onset off lecainide (1 μmol/L) blocking were 0.586, 0.128, 0.071, 0.042 and 0.030AP^-1 at stimulation frequencies of 0.1, 0.5, 1.0, 2.0 and 3.3 Hz, respectively. The estimated time constant of recovery from block by flecainide was 17.45 s. These results are in agreement with documented experimental data. The analysis of gate-related receptor showed that the binding and unbinding of flecainide is modulated by anactivation process. No shift of h∞ curve but a significant decrease of m³∞ curve was found in the presence of flecainide (1 μmol/L). These findings sugnficant that flecainide binds to the activation gate-related receptor, and may be trapped in the channel by the activation gate.

Key words: Fleainide, Sodium channel, Antiarrhythmic agents, Computer simulation, Gaterelated receptor

Supporting:

吴跃进. 氟卡胺与心肌钠通道相互作用的模拟分析[J]. .

Yue-Jin Wu. Modelling and Analysis of Interactions of Flecainid with Cardiac Sodium Channels[J]. .