title: Selective phenylalkylamine block of I(Kr) over other K(+) currents in guinea-pig ventricular myocytes.
abstract: Previous studies on verapamil and D600 have established that the Ca(2+)-channel blockers also inhibit delayed-rectifier K(+) currents in cardiac tissues and myocytes. However, estimated IC(50) values range over two to three orders of concentration, and it is unclear whether this reflects a high selectivity by one or both of the phenylalkylamines for particular K(+) channels. The purpose of the present study was to determine the concentration-dependent actions of verapamil and D600 on three defined cardiac K(+) currents. Guinea-pig ventricular myocytes in the conventional whole-cell configuration were bathed with normal Tyrode's or K(+)-free solution, and pulsed from -80 mV for measurement of the effects of 0.01 microM to 3 mM verapamil and D600 on the inwardly-rectifying K(+) current (I:(Kl)) and the two delayed-rectifier K(+) currents, rapidly-activating I:(Kr) and slowly-activating I:(Ks). The phenylalkylamines inhibited both inward- and outward-directed I:(Kl). The IC(50) values for outward I:(Kl) were approximately 220 microM. Verapamil and D600 were approximately equipotent inhibitors of the delayed-rectifier K(+) currents. They inhibited I:(Kr) with IC(50) near 3 microM, and I:(Ks) with IC(50) > or =280 microM. These results are discussed in relation to previous findings on K(+) currents and to the clinical actions of the drugs.
authors.affiliation: Department of Physiology and Biophysics, Dalhousie University, Halifax, Nova Scotia, B3H 4H7, Canada.
authors.forename: S E
authors.initials: SE
authors.lastname: Jones
authors.forename: S
authors.initials: S
authors.lastname: Missan
authors.forename: P
authors.initials: P
authors.lastname: Zhabyeyev
authors.forename: T F
authors.initials: TF
authors.lastname: McDonald
mesh_terms: D000818:Animals; D002121:Calcium Channel Blockers / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D005711:Gallopamil / Q000494:pharmacology; D006168:Guinea Pigs; D006352:Heart Ventricles / Q000166:cytology / Q000187:drug effects*; D008297:Male; D008564:Membrane Potentials / Q000187:drug effects*; D010627:Phenethylamines / Q000494:pharmacology*; D015221:Potassium Channels / Q000502:physiology*; D013997:Time Factors; D016276:Ventricular Function; D014700:Verapamil / Q000494:pharmacology
chemical_list: D002121:Calcium Channel Blockers; D010627:Phenethylamines; D015221:Potassium Channels; D005711:Gallopamil; D014700:Verapamil