Quantitative modelling of interaction of propafenone with sodium channels in cardiac cells.
|Year of publication||2001|
|Type||Article in Proceedings|
|Conference||Proceedings of the International Federation for Medical and Biologocal Engineering|
|MU Faculty or unit|
|Keywords||cardiac cell; propafenone; quantitative modelling|
|Description||A mathematical model of the interaction of propafenone with sodium channels is based on experimental data that demonstrate use dependent effect of the drug. Transitions among channel states are described by a kinetic diagram and a corre-sponding set of differential equations. The values of rate constants of the drug-receptor reaction are fitted to experimental data by repeated computer simulations using a genetic algorithm. The model suggests the following interpretation of the obtained experimental results: 1) The affinity of the drug to its binding site is high in the open and inactivated states while it is low in the resting state. 2) The biphasic development of the block during depolarization is consistent with a high association rate constant in the open state and a lower one in the inactivated state. 3) The observed double exponential time course of recovery of INa at resting voltage after depolarizing pulse may result from concurrent drug release from inactivated and non-inactivated blocked channels.|