氟卡尼与心肌钠通道相互作用的模拟分析

MODELLING AND ANALYSIS OF INTERACTIONS OF FLECAINIDE WITH CARDIAC SODIUM CHANNELS

根据闸门相关受体假说，应用计算机模拟分析了氟卡尼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。模型预测的氟卡尼（１μｍｏｌ／Ｌ）在刺激频率０．１，０．５，１．０，２．０和３．３ＨＺ时的表观阻滞起效速率分别为０．５８６，０．１２８，０．０７１，０．０４２和０．０３０ＡＰ－１，静息阻滞恢复时间常数为１７．４ｓ，这些均与文献报道的实验数据一致。对氟卡尼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，氟卡尼１μｍｏｌ／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。

Based on the ante-rebated receptor hypothesis, modelling and analysis of the kinetics of interactions of flecainide with catdiac sodium Channels and the gate-related receptor bound by the drug were performed by computer simulation. Model-predicted apparent rates of onset of flecainide (1 μmol·L-1) blocking were 0. 586, 0. 128, 0. 071. 0. 042 and 0. 030 AP-1 resistively at stimulation frequencies of 0. 1, 0. 5, 1. 0, 2. 0, and 3. 3 Hz. The estimated time constant of recovery from block by flecainide was 17. 45 s. These results are in agreement with documented experimental data. Analysis of gate-related receptor showed that the binding and unbinding of flecainide are modulated by activation process. No shift of h∞ curve but a significant decrease of m∞3 curve was found in the presence of flecainide (1 μmol·L-1 ). The results suggest that fleCainide binds to the activation gate-related receptor and may be trapped in the channel by the activation gate.