PT  - JOURNAL ARTICLE
AU  - M. J. Hernandez-Benito
AU  - R. Macianskiene
AU  - K. R. Sipido
AU  - W. Flameng
AU  - K. Mubagwa
TI  - Suppression of Transient Outward Potassium Currents in Mouse Ventricular Myocytes by Imidazole Antimycotics and by Glybenclamide
DP  - 2001 Aug 01
TA  - Journal of Pharmacology and Experimental Therapeutics
PG  - 598--606
VI  - 298
IP  - 2
4099  - http://jpet.aspetjournals.org/content/298/2/598.short
4100  - http://jpet.aspetjournals.org/content/298/2/598.full
SO  - J Pharmacol Exp Ther2001 Aug 01; 298
AB  - The whole-cell patch-clamp technique was used in adult mouse ventricular myocytes at 22°C to study the transient outward current (Ito) and its sensitivity to the antimycotics miconazole and clotrimazole, as well as to glybenclamide. Ito elicited by depolarizing steps from a holding potential of −80 mV consisted of a fast inactivating component and a slowly inactivating component. In the presence of miconazole (IC50 of ≈8 μM) or clotrimazole, Ito peak amplitude was reduced and its inactivation accelerated, 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 application, and occurred without a change of the steady-state inactivation. In the presence of glybenclamide Ito peak amplitude was reduced and its inactivation accelerated. In contrast to the antimycotics, glybenclamide suppressed both the fast and the slow components (IC50 of ≈50 μM), its effect was reversible, and was associated with a negative shift of the steady-state inactivation. These data demonstrate a pharmacological separation of Itocomponents using antimycotic drugs but not glybenclamide. The American Society for Pharmacology and Experimental Therapeutics