Uchino Tomoko, Lee Tae-Seong, Kaku Toshihiko, Yamashita Noboru, Noguchi Takayuki, Ono Katsushige
Department of Cardiovascular Science, Oita University, Oita, Japan.
Pharmacology. 2005 Jul;74(4):174-81. doi: 10.1159/000085329. Epub 2005 Apr 25.
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.
采用膜片钳技术研究了苄普地尔对稳定表达于人类胚胎肾（HEK）-293细胞中的低电压激活T型Ca2+通道（CaV3.2）电流的影响。苄普地尔以明显的电压依赖性方式强力抑制ICa,T；在-70 mV的钳制电位下，苄普地尔的IC50为0.4 μmol/L，其效力是在-100 mV（10.6 μmol/L）时的26倍。10 μmol/L苄普地尔使稳态失活曲线（8.4±1.7 mV）和电导曲线（5.9±1.9 mV）向超极化电位移动。苄普地尔发挥的是强直阻断作用而非使用依赖性阻断。苄普地尔对T型Ca2+通道的失活恢复没有影响。因此，苄普地尔终止心房颤动和心房扑动的高效能可能至少部分归因于其对T型Ca2+通道的阻断作用。
