Okabe K, Terada K, Kitamura K, Kuriyama H
Department of Pharmacology, Faculty of Medicine, Kyushu University, Fukuoka, Japan.
J Pharmacol Exp Ther. 1987 Nov;243(2):703-10.
Effects of CV-4093, a newly synthesized dihydropiridine type of Ca antagonist, on membrane currents in enzymatically dispersed single smooth muscle cells of the rabbit main pulmonary artery were investigated using the single electrode voltage clamp method. Three types of membrane currents were evident, i.e., Ca and Na inward and K outward currents. CV-4093 potently inhibited the Ca inward current, as compared to findings with other currents. When the potential was at -60 mV, CV-4093 consistently inhibited the Ca current evoked by depolarization to 0 mV. However, a low concentration of CV-4093 (1-3 nM) enhanced the Ca current evoked by the depolarizing pulse of -20 mV, when the membrane potential was held at -80 mV. Inhibition of the Ca current induced by CV-4093 developed slowly and over 10 min was required to reach the maximum inhibition. Changes in the frequency of the depolarizing pulse did not modify the rate of inhibition induced by CV-4093. The inhibition was not restored by washout of the drug for over 40 min, and hyperpolarizations of the membrane did not accelerate the recovery. The IC50 of CV-4093 obtained for the K outward current was 3000 times larger than that obtained for the Ca inward current. CV-4093 apparently has highly selective and long-lasting inhibitory actions on the Ca current in smooth muscle cells of the rabbit main pulmonary artery.
采用单电极电压钳法，研究了新合成的二氢吡啶类钙拮抗剂CV - 4093对兔主肺动脉酶分散单个平滑肌细胞膜电流的影响。明显存在三种类型的膜电流，即钙和钠内向电流以及钾外向电流。与其他电流的研究结果相比，CV - 4093能有效抑制钙内向电流。当电位为 - 60 mV时，CV - 4093持续抑制去极化至0 mV所诱发的钙电流。然而，当膜电位保持在 - 80 mV时，低浓度的CV - 4093（1 - 3 nM）增强了 - 20 mV去极化脉冲所诱发的钙电流。CV - 4093诱导的钙电流抑制作用发展缓慢，需要超过10分钟才能达到最大抑制。去极化脉冲频率的变化并未改变CV - 4093诱导的抑制速率。药物洗脱超过40分钟后抑制作用仍未恢复，膜的超极化也未加速恢复。CV - 4093对钾外向电流的IC50比对钙内向电流的IC50大3000倍。CV - 4093对兔主肺动脉平滑肌细胞的钙电流显然具有高度选择性和持久的抑制作用。
