Publication details
Quantitative modelling of interaction of propafenone with sodium channels in cardiac cells
| Authors | |
|---|---|
| Year of publication | 2004 |
| Type | Article in Periodical |
| Magazine / Source | Medical & Biological Engineering & Computing |
| MU Faculty or unit | |
| Citation | |
| Field | Biophysics |
| Keywords | cardiac cell; sodium current block; propafenone; quantitative modelling |
| Description | A mathematical model of the interaction of propafenone with cardiac sodium channels is based on experimental data that demonstrate use-dependent effect of the drug. The model of CLANCY and RUDY (Circulation, 2002; 105: 1208-1213) is applied to describe Na-channel 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 that drug molecules have an access to the binding sites predominantly in the inactivated states and that accumulation of blocked channels in the slow inactivated state is responsible for the observed use- dependent effects. The results of quantitative modelling predict that propafenone (0.2 mmol/l) effectively suppresses premature excitations leaving the regular action potentials nearly unaffected. |
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