Estimation of rate constants of drug binding to open channels of cardiac transient outward current

Jiří Šimurda, Milena Šimurdová
2012 General Physiology and Biophysics  
An improved approach to the evaluation of the rate constants of drugs binding to the open channel underlying the transient outward potassium current I to 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 to by two exponentials in the absence and by three exponentials in the
more » ... nentials in the presence of a blocking agent. The model study confirmed significantly higher accuracy in comparison with the existing electrophysiological method. Abbreviations: α q , β q , rate constants of activation; α r , β r , rate constants of fast inactivation; α s , β s , rate constants of slow inactivation; [D], drug concentration; I to , transient outward current; k on , k off , rate constants of drug binding; Kv4.3, a phenotype of I to channel; τ bf , τ bs , τ bus , fast, slow and ultraslow time constants of apparent inactivation in the presence of a drug; τ i , τ if , τ is , time constants of inactivation; V, membrane voltage.
doi:10.4149/gpb_2012_013 pmid:22447837 fatcat:vqe7gguouzardgnxjpt4mvjbmm