A GATE—RELATED RECEPTOR ANALYSIS OF CARDIAC SODIUM CHANNEL BLOKADE BY QUINIDINE

Based on the gate-related receptor hypothesis ,an analysis of the kinetics of interac-tions of quinidine with cardiac sodium channels and the gate- related receptor bound by the drug wasperformed by computer simulation. Medel-predicted apparent rates of onset of quinidine(15μmol/L)blocking were shown to be 0. 613,0.371,0.274,0.226 and 0.201 Ap^-1 respectively at stimula-tion frequencies of0.5,1.0,1 67,2.5 and 3.3 Hz. The estimated time constant of recovery fromblock by quinidine was 4.13 s.These results are in agreement with documented experimental data.Analysis of gating process dependent block by quinidine showed that the block depends on the activa-tion gating process.No shift of h_∞curve but a significant decrease of m³_∞ curve was found in thepresence of quinidine(15μmol/L).The results suggest that quinidine binds to the activation gate-related reeeptor ,and might be trapped in the channel by the activation gate. The binding and unbind-ing of quinidine are modulated by the activation process.