Antiarrhythmic and bradycardic drugs inhibit currents of cloned K+ channels, KV1.2 and KV1.4.
We investigated the effects of the antiarrhythmic drugs, quinidine, disopyramide, flecainide, clofilium, verapamil, and the bradycardic drug, bertosamil, on the currents of the cloned K+ channels, KV1.2 (IK(V1.2)) and KV1.4 (IK(V1.4)), using the Xenopus oocyte expression system. Both IK(V1.2) and IK(V1.4) were inhibited in a concentration-dependent manner by quinidine (10 microM to 1 mM), flecainide (10 microM to 1 mM), clofilium (10-300 microM), verapamil (10 microM to 1 mM) and bertosamil (10 microM to 1 mM) but not by disopyramide (10 microM to 1 mM). The inhibitory effects of clofilium, verapamil and bertosamil on IK(V1.2) were time-dependent. The decay time course of IK(V1.4) was accelerated by clofilium, verapamil and bertosamil, but decelerated by quinidine and flecainide. These results indicate that IK(V1.2) and IK(V1.4) are targets for the four antiarrhythmic drugs and the bradycardic drug.
Yamagishi
T
T
Department of Pharmacology, Tohoku University School of Medicine, Sendai, Japan.
Ishii
K
K
Taira
N
N
D000818:Animals; D000889:Anti-Arrhythmia Agents / Q000494:pharmacology*; D001919:Bradycardia / Q000209:etiology; D003001:Cloning, Molecular; D004206:Disopyramide / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D008433:Mathematics; D009865:Oocytes; D015221:Potassium Channels / Q000187:drug effects*; D000644:Quaternary Ammonium Compounds / Q000494:pharmacology; D011802:Quinidine / Q000494:pharmacology; D014700:Verapamil / Q000494:pharmacology; D014982:Xenopus laevis
D000889:Anti-Arrhythmia Agents; D015221:Potassium Channels; D000644:Quaternary Ammonium Compounds; C022799:clofilium; D014700:Verapamil; D004206:Disopyramide; D011802:Quinidine