[Modelling and analysis of interactions of flecainide with cardiac sodium channels].
Based on the gate-related receptor hypothesis, modelling and analysis of the kinetics of interactions of flecainide with cardiac 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 mumol.L-1) blocking were 0.586, 0.128, 0.071, 0.042 and 0.030 AP-1 respectively 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 infinity curve but a significant decrease of m infinity 3 curve was found in the presence of flecainide (1 mumol.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.
Wu
Y J
YJ
Department of Pharmacology, Guangdong Medical College, Zhanjiang.
D000200:Action Potentials; D000818:Animals; D003198:Computer Simulation; D005424:Flecainide / Q000494:pharmacology*; D006168:Guinea Pigs; D006321:Heart / Q000502:physiology*; D015640:Ion Channel Gating / Q000187:drug effects*; D008564:Membrane Potentials; D009206:Myocardium / Q000378:metabolism; D015222:Sodium Channels / Q000378:metabolism*
D015222:Sodium Channels; D005424:Flecainide