NDLI: Quantitative modelling of interaction of propafenone with sodium channels in cardiac cells

Content Provider	Springer Nature Link
Author	Pásek, M. Ŝimurda, J.
Copyright Year	2004
Abstract	A mathematical model of the interaction of propafenone with cardiac sodium channels is based on experimental data that demonstrate use-dependent effects of the drug. The Clancy-Rudy model is applied to describe Na-channels in absence of the drug. The values of rate constants of the drug-receptor reaction are fitted to experimental data by iterative computer simulations using a genetic algorithm. The model suggests the following interpretation of available experimental results: First, drug molecules have access to the binding sites predominantly in the inactivated states. Secondly, the biphasic development of the block during depolarisation is consistent with a rapid increase due to drug binding in the fast inactivated state (rate constants k$_{on}$=645μmol$^{−1}$ ls$^{−1}$, k$_{off}$=16.21 s$^{−1}$) and a slow increase due to binding in the intermediate inactivated state (rate constants ∼100-fold lower), followed by transition to the drug-occupied slow inactivated state (rate constants 0.784 and 0.921 s$^{−1}$). Thirdly, the observed biphasic time course of recovery of I$_{Na}$ from block following restoration of the resting voltage results from simultaneous relief of block from the channels residing in the intermediate and slow inactivated states. Fourthly, the accumulation of blocked channels in the slow inactivated state is responsible for the observed use-dependent effects. Fifthly, when incorporated into a quantitative description of the electrical activity of a ventricular cell, the model predicts that propafenone (0.2μmol l$^{−1}$) effectively suppresses premature excitations, leaving the regular action potentials nearly unaffected.
Starting Page	151
Ending Page	157
Page Count	7
File Format	PDF
ISSN	01400118
Journal	Medical and Biological Engineering and Computing
Volume Number	42
Issue Number	2
e-ISSN	17410444
Language	English
Publisher	Springer-Verlag
Publisher Date	2004-01-01
Publisher Place	Berlin, Heidelberg
Access Restriction	One Nation One Subscription (ONOS)
Subject Keyword	Cardiac cell Sodium current block Propafenone Quantitative modelling Genetic algorithm Human Physiology Computer Applications Neurosciences Imaging Radiology Biomedical Engineering
Content Type	Text
Resource Type	Article
Subject	Biomedical Engineering Computer Science Applications

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