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Cogolludo AL, Perez-Vizcaino F, Lopez-Lopez G, Ibarra M, Zaragoza-Arnaez F, Tamargo J: Propafenone modulates potassium channel activities of vascular smooth muscle from rat portal veins. J Pharmacol Exp Ther. 2001 Nov;299(2):801-10.
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 microM) 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 microM). Inhibition of I (Ktotal) by propafenone was concentration-dependent (EC50 = 0.059 +/- 0.009 microM). Propafenone also inhibited the transient outward current [I (K (A))] and ATP-sensitive potassium current [I (K (ATP))] induced by levcromakalim (10 microM). Inhibition of I (K (V)), I (K (A)), and I (K (ATP)) by propafenone was voltage-independent. In Ca (2+)-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. |
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