[A gate-related receptor analysis of cardiac sodium channel blockade by quinidine].
Based on the gate-related receptor hypothesis, an analysis of the kinetics of interactions of quinidine with cardiac sodium channels and the gate-related receptor bound by the drug was performed by computer simulation. Model-predicted apparent rates of onset of quinidine (15 mumol/L) blocking were shown to be 0.613, 0.371, 0.274, 0.226 and 0.201 AP-1 respectively at stimulation frequencies of 0.5, 1.0, 1.67, 2.5 and 3.3 Hz. The estimated time constant of recovery from block 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 activation gating process. No shift of h infinity curve but a significant decrease of m3 infinity curve was found in the presence of quinidine (15 mumol/L). The results suggest that quinidine binds to the activation gate-related receptor, and might be trapped in the channel by the activation gate. The binding and unbinding of quinidine are modulated by the activation process.
Wu
Y J
YJ
Department of Pharmacology, Guangdong Medical College, Zhanjiang.
D000818:Animals; D006168:Guinea Pigs; D006321:Heart / Q000502:physiology*; D015640:Ion Channel Gating; D007700:Kinetics; D008564:Membrane Potentials; D008956:Models, Chemical; D009206:Myocardium / Q000378:metabolism; D011802:Quinidine / Q000494:pharmacology*; D011955:Receptors, Drug; D015222:Sodium Channels / Q000187:drug effects*
D011955:Receptors, Drug; D015222:Sodium Channels; D011802:Quinidine