Publication detail

Quantitative modelling of interaction of propafenone with sodium channels in cardiac cells.

PÁSEK, M. ŠIMURDA, J.

English title

Quantitative modelling of interaction of propafenone with sodium channels in cardiac cells.

Type

conference paper

Language

en

Original abstract

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.

English abstract

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.

Keywords in English

cardiac cell, propafenone, quantitative modelling

Released

01.01.2001

Publisher

Faculty of Electrical Engineering, Zagreb

Location

Pula, Chorvatsko

ISBN

1680-0737

Book

IFMBE Proceedings

Pages count

4

BIBTEX


@inproceedings{BUT5879,
  author="Michal {Pásek} and Jiří {Šimurda},
  title="Quantitative modelling of interaction of propafenone with sodium channels in cardiac cells.",
  booktitle="IFMBE Proceedings",
  year="2001",
  month="January",
  publisher="Faculty of Electrical Engineering, Zagreb",
  address="Pula, Chorvatsko",
  isbn="1680-0737"
}