Voltage-dependent and frequency-independent inhibition of recombinant Cav3.2 T-type Ca2+ channel by bepridil.
Effects of bepridil on the low voltage-activated T-type Ca2+ channel (CaV3.2) current stably expressed in human embryonic kidney (HEK)-293 cells were examined using patch-clamp techniques. Bepridil potently inhibited ICa,T with a markedly voltage-dependent manner; the IC50 of bepridil was 0.4 micromol/l at the holding potential of -70 mV, which was 26 times as potent as that at -100 mV (10.6 micromol/l). Steady-state inactivation curve (8.4 +/- 1.7 mV) and conductance curve (5.9 +/- 1.9 mV) were shifted to the hyperpolarized potential by 10 micromol/l bepridil. Bepridil exerted the tonic blocking action but not the use-dependent block. Bepridil had no effect on the recovery from inactivation of T-type Ca2+ channels. Thus, high efficacy of bepridil for terminating atrial fibrillation and atrial flutter may be considered to be attributed, at least in a part, to the T-type Ca2+ channel-blocking actions.
Uchino
Tomoko
T
Department of Cardiovascular Science, Oita University, Oita, Japan.
Lee
Tae-Seong
TS
Kaku
Toshihiko
T
Yamashita
Noboru
N
Noguchi
Takayuki
T
Ono
Katsushige
K
D015764:Bepridil / Q000494:pharmacology*; D002121:Calcium Channel Blockers / Q000494:pharmacology*; D020746:Calcium Channels, L-Type / Q000235:genetics / Q000502:physiology*; D002460:Cell Line; D004305:Dose-Response Relationship, Drug; D004558:Electric Stimulation; D005822:Genetic Vectors / Q000235:genetics; D006801:Humans; D008564:Membrane Potentials / Q000187:drug effects; D018408:Patch-Clamp Techniques; D013997:Time Factors; D014162:Transfection
D002121:Calcium Channel Blockers; D020746:Calcium Channels, L-Type; D015764:Bepridil