Vol. 298, Issue 2, 598-606, August 2001

Suppression of Transient Outward Potassium Currents in Mouse Ventricular Myocytes by Imidazole Antimycotics and by Glybenclamide

M. J. Hernandez-Benito , R. Macianskiene , K. R. Sipido, W. Flameng and K. Mubagwa

Laboratory of Cardiac Cellular Research, Centre for Experimental Surgery and Anaesthesiology (M.J.H.-B., R.M., W.F., K.M.), and Laboratory of Experimental Cardiology (K.R.S.), University of Leuven, Leuven, Belgium

The whole-cell patch-clamp technique was used in adult mouse ventricular myocytes at 22°C 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 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, I_to 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 I_to 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 I_to components using antimycotic drugs but not glybenclamide.