Inhibitory effect of bepridil on hKv1.5 channel current: comparison with amiodarone and E-4031

Effects of bepridil on the depolarization-activated outward K+ currents in rat atrial myocytes and the human cardiac K+ (hKv1.5) channel current stably expressed in human embryonic kidney (HEK) 293 cells were examined, and compared with those of amiodarone and N-[4-[[1-[2-(6-methyl-2-pyridinyl)ethyl]-4-piperidinyl]carbonyl]phenyl] methanesulphonamide dihydrochloride dihydrate (E-4031). Membrane currents were recorded using patch-clamp techniques in enzymatically isolated rat atrial myocytes and HEK 293 cells expressing hKv1.5 channels. Bepridil potently inhibited I-out elicited by depolarization pulses and prolonged the action potential in rat atrial cells. Bepridil also inhibited the hKvl.5 channel current with the IC50 value of 6.6 muM. The inhibitory effects of bepridil on the currents in HEK 293 cells were voltage-dependent. Amiodarone weakly inhibited rat atrial I-out and hKv1.5 channel current. In. contrast, E-4031 at a concentration of 10 muM had little influence on these currents. Thus, bepridil inhibits hKvl.5 channel current and the inhibitory effect may be useful for the treatment of atrial fibrillation. (C) 2001 Elsevier Science B.V. All rights reserved.