Propafenone modulates potassium channel activities of vascular smooth muscle from rat portal veins.
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.
Cogolludo
A L
AL
Department of Pharmacology, Institute of Pharmacology and Toxicology, School of Medicine, Universidad Complutense, Madrid, Spain. acogolludo@ift.csic.es
Pérez-Vizcaíno
F
F
López-López
G
G
Ibarra
M
M
Zaragozá-Arnáez
F
F
Tamargo
J
J
D000818:Animals; D000889:Anti-Arrhythmia Agents / Q000494:pharmacology*; D004594:Electrophysiology; D066298:In Vitro Techniques; D008297:Male; D008564:Membrane Potentials / Q000187:drug effects; D009119:Muscle Contraction / Q000187:drug effects; D009131:Muscle, Smooth, Vascular / Q000187:drug effects*; D011169:Portal Vein / Q000187:drug effects*; D026902:Potassium Channel Blockers; D015221:Potassium Channels / Q000187:drug effects*; D011405:Propafenone / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar
D000889:Anti-Arrhythmia Agents; D026902:Potassium Channel Blockers; D015221:Potassium Channels; D011405:Propafenone