Suppression of transient outward potassium currents in mouse ventricular myocytes by imidazole antimycotics and by glybenclamide

The whole-cell patch-clamp technique was used in adult mouse ventricular my ocytes at 22 degreesC to study the transient outward current (I-to) and its sensitivity to the antimycotics miconazole and clotrimazole, as well as to glybenclamide. I-to elicited by depolarizing steps from a holding potentia l of -80 mV consisted of a fast inactivating component and a slowly inactiv ating component. In the presence of miconazole (IC50 of approximate to8 muM ) or clotrimazole, I-to peak amplitude was reduced and its inactivation acc elerated, due to a selective suppression of the slow component, without an effect on the fast component or on the noninactivating current. The effect did not reverse upon washout, was not induced by intracellular drug applica tion, and occurred without a change of the steady-state inactivation. In th e presence of glybenclamide I-to peak amplitude was reduced and its inactiv ation accelerated. In contrast to the antimycotics, glybenclamide suppresse d both the fast and the slow components (IC50 of approximate to 50 muM), it s effect was reversible, and was associated with a negative shift of the st eady-state inactivation. These data demonstrate a pharmacological separatio n of I-to components using antimycotic drugs but not glybenclamide.