Key result
A mathematical model using three exponentials to approximate the time course of apparent inactivation of Ito significantly improved the accuracy of estimated drug binding rate constants.
An improved 12-equation mathematical model provides significantly higher accuracy for estimating the rate constants of drug binding to open Ito channels compared to traditional simplified methods.
Enhances precision of Ito binding kinetics in models; extends computational methods but leaves open validation in human myocytes.
An improved approach to the evaluation of the rate constants of drugs binding to the open channel underlying the transient outward potassium current I(t0) is described. It is based on an analysis of a quantitative model formulated by a set of twelve differential equations. The rate constants are calculated from the time constants resulting from an approximation of the time course of apparent inactivation of the recorded I(t0) by two exponentials in the absence and by three exponentials in the presence of a blocking agent. The model study confirmed significantly higher accuracy in comparison with the existing electrophysiological method.
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Šimurda et al. (2012) studied Cardiac transient outward current (Ito) drug binding. Mathematical model using three exponentials vs. Existing electrophysiological method (one or two exponentials) was evaluated on Accuracy of estimated rate constants (kon, koff). A mathematical model using three exponentials to approximate the time course of apparent inactivation of Ito significantly improved the accuracy of estimated drug binding rate constants.
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