Vol. 299, Issue 2, 801-810, November 2001

Propafenone Modulates Potassium Channel Activities of Vascular Smooth Muscle from Rat Portal Veins

Angel L. Cogolludo, Francisco Pérez-Vizcaíno, Gustavo López-López, Manuel Ibarra, Francisco Zaragozá-Arnáez and Juan Tamargo

Department of Pharmacology, Institute of Pharmacology and Toxicology (Consejo Superior de Investigaciones Cientificas), School of Medicine, Universidad Complutense, Madrid, Spain

We have studied the effects of the class Ic antiarrhythmic propafenone on K⁺ currents in freshly isolated smooth muscle cells from rat portal veins and on the spontaneous contractions in whole tissues. Under Ca²⁺-free conditions, when cells were clamped at 80 mV (whole-cell configuration) depolarizing steps from 80 to +50 mV induced a family of K⁺ currents (I_Ktotal) that mainly comprised the delayed rectifier current [I_K(V)], whereas when held at 10 mV only small-amplitude, noninactivating, currents (I_NI) were recorded. Propafenone (10 µM) markedly inhibited I_Ktotal, but at potentials positive to +30 mV it also induced a noisy outwardly rectifying current [I_BK(Ca)] that was abolished by iberiotoxin (0.1 µM). Inhibition of I_Ktotal by propafenone was concentration-dependent (EC₅₀ = 0.059 ± 0.009 µM). Propafenone also inhibited the transient outward current [I_K(A)] and ATP-sensitive potassium current [I_K(ATP)] induced by levcromakalim (10 µM). Inhibition of I_K(V), I_K(A), and I_K(ATP) by propafenone was voltage-independent. In Ca²⁺-containing conditions propafenone inhibited I_K(V) and I_BK(Ca) and immediately abolished spontaneous outward transient K⁺ currents. In whole veins, propafenone behaved as the K_V inhibitor 4-aminopyridine, increasing the amplitude and duration of spontaneous contractions. Propafenone also inhibited the inhibitory effects of the K_ATP channel opener levcromakalim on spontaneous contractions. These results indicate that in vascular smooth muscle cells, propafenone inhibits K_V, K_A, BK_Ca, and K_ATP channels. These actions correlated with its effects on mechanical activity in whole portal veins.