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 (I(out)) 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 hKv1.5 channel current with the IC(50) value of 6.6 microM. 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 microM had little influence on these currents. Thus, bepridil inhibits hKv1.5 channel current and the inhibitory effect may be useful for the treatment of atrial fibrillation.
Kobayashi
S
S
Department of Cardiovascular Science and Medicine, Chiba University Graduate School of Medicine, 1-8-1 Inohana, Chuo-ku, 260-8670, Chiba, Japan.
Reien
Y
Y
Ogura
T
T
Saito
T
T
Masuda
Y
Y
Nakaya
H
H
D015761:4-Aminopyridine / Q000494:pharmacology; D000200:Action Potentials / Q000187:drug effects; D000638:Amiodarone / Q000494:pharmacology; D000818:Animals; D000889:Anti-Arrhythmia Agents / Q000494:pharmacology*; D016275:Atrial Function; D015764:Bepridil / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D015870:Gene Expression; D006325:Heart Atria / Q000166:cytology / Q000187:drug effects; D006801:Humans; D066298:In Vitro Techniques; D051666:Kv1.5 Potassium Channel; D008564:Membrane Potentials / Q000187:drug effects*; D018408:Patch-Clamp Techniques; D010880:Piperidines / Q000494:pharmacology; D026902:Potassium Channel Blockers / Q000494:pharmacology; D015221:Potassium Channels / Q000235:genetics / Q000502:physiology*; D024642:Potassium Channels, Voltage-Gated; D011725:Pyridines / Q000494:pharmacology; D051381:Rats
D000889:Anti-Arrhythmia Agents; C496981:KCNA5 protein, human; C496983:Kcna5 protein, rat; D051666:Kv1.5 Potassium Channel; D010880:Piperidines; D026902:Potassium Channel Blockers; D015221:Potassium Channels; D024642:Potassium Channels, Voltage-Gated; D011725:Pyridines; C063968:E 4031; D015764:Bepridil; D015761:4-Aminopyridine; D000638:Amiodarone