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选择性L型钙通道阻断剂硝苯地平 (Nif)为常用的工具药 ,因此必须了解它对L型钙流 (ICa(L) )浓度、状态依赖性阻断 ,使用和非使用依赖性阻断等特性。以豚鼠分离的单个心室肌细胞为对象 ,采用膜片钳全细胞记录技术 ,给予 35℃的各种含药物细胞外液快速灌流 ,记录ICa(L) 。结果 :①保持电位 - 80mV ,使用含铯离子的细胞内、外液 ,在 +10mV的钳制电压 ,Nif抑制ICa(L) 的IC50 为 0 .3μmol·L-1;当保持电位为 - 40mV时 ,IC50 为 0 .0 5 μmol·L-1,显示Nif优先选择与失活态钙通道结合。②使用富含钾离子的细胞内、外液 ,对ICa(L) 的非使用依赖性阻断 ,随Nif使用浓度 (30～ 10 0 μmol·L-1)的增加和药物作用时间的延长而加强 ,同时对ICa(L) 的使用依赖性阻断则减小。③在 10s的静息间隔药物作用时间后的第一个实验刺激 ,Nif 3μmol·L-1或 30 μmol·L-1加速ICa(L) 的失活 ,提示Nif对ICa(L) 可能存在激活态阻断。结论 :在生理条件下 ,Nif对ICa(L) 的阻断呈浓度、状态依赖性 ,对ICa(L) 的非使用依赖性阻断随使用浓度的增加和作用时间的延长而加强 ,对ICa(L) 的使用依赖性阻断则随之减弱。
The selective L-type calcium channel blocker, nifedipine (Nif), is a commonly used tool and therefore it is important to understand its effect on L-type calcium flux (ICa (L)) concentration, state-dependent blockade, Blocking and other features. Single ventricular myocytes isolated from guinea pigs were used as target. Whole-cell patch-clamp recording technique was used to rapidly perfuse various drug-containing extracellular fluid at 35 ℃ and record ICa (L). The IC50 of Nif inhibition ICa (L) was 0.3μmol·L-1 at a holding potential of -80mV, using a cesium ion-containing intracellular and extracellular fluid at a clamping voltage of +10 mV. When the holding potential was -40mV , With an IC50 of 0.05 μmol·L-1, indicating that Nif preferentially binds to an inactive calcium channel. ② The use of potassium-rich intracellular and extracellular fluids blocked the non-use-dependent inhibition of ICa (L). With the increase of the concentration of Nif (30 ~ 100 μmol·L-1) and the prolongation of the drug action , While the use-dependent blockade of ICa (L) decreases. (3) Nif 3μmol·L-1 or 30 μmol·L-1 accelerated the ICa (L) inactivation at the interval of 10s, suggesting that Nif could activate ICa (L) State blocked. CONCLUSIONS: Under physiological conditions, Nif inhibits ICa (L) concentration in a concentration and state-dependent manner. The non-use-dependent blockade of ICa (L) is enhanced with increasing concentration and prolongation of action time. (L) use-dependent blockage will be weakened.