摘要
根据闸门相关受体假说,应用计算机模拟,分析了新抗心律失常药AN-132阻滞心肌钠通道的动力学特点,及其作用的闸门相关受体。模型预测的AN-132(30μmol/L)在刺激频率1.0、2.0和3.0H_z时的表观阻滞起效速率,分别为0.051、0.038和0.034AP^(-1),在膜电位为-90mV时的阻滞恢复时间常数为39.5s,这些均与文献报道的实验数据一致。对AN-132作用的闸门相关受体分析,表明其作用于失活门相关受体,其与受体结合与解离均受失活过程调控。
Based on the gate-related receptor hypothesis,an analysis on kinetics of AN-132,a new antiarrhythmic agent, blockade of cardiac sodium channels and the gate-related receptor which be bound by the drug was performed by computer simulation. Model-predicted apparent rates of onset of AN-132(30 μmol/L)blocking were 0. 051,0. 038 and 0. 034 AP-1 at stimulation frequencies of 1. 0,2. 0 and 3. 0 Hz respectively. The time constant of recovery from block by AN-132 at resting potential-90 mV was 39. 5s. These results are in agreement with documented experimental data. The analysis of gate-related receptor showed that AN-132 binds to the inactivation gate-related receptor ,and the binding and unbinding are modulated-by inactivation process.
基金
国家自然科学基金
关键词
AN-132
抗心律失常药
钠通道
受体
AN-132
antiarrhythmic drug
sodium channel
computer simulation
receptors, drug
gate-related receptor
