Hering S, Beech D J, Bolton T B, Lim S P
Department of Pharmacology and Clinical Pharmacology, St. George's Hospital Medical School, London, Great Britain.
Pflugers Arch. 1988 May;411(5):590-2. doi: 10.1007/BF00582383.
The actions of nifedipine or BAY K 8644 were studied on barium currents recorded from single, collagenase- and elastase-dispersed, smooth muscle cells from the rabbit ear artery using the whole-cell configuration of the patch-clamp technique. Nifedipine (3 microM) caused a reduction in the barium current (IBa) evoked by steps to potentials positive of -10 mV. This was characterized by a pronounced 'initial' block, an increase in the rate of current decay during the voltage-clamp step, but by no increase in block if pulses were repeated every 600 ms. Rapid extracellular application of nifedipine (1 microM) during the sustained current component (using a new concentration-jump technique) was found to have no effect on IBa over 4s at +20 mV, but after returning to the holding potential (-60 mV) for 10s, sustained IBa was subsequently abolished. BAY K 8644 (1 microM) increased IBa at all potentials, and on rapid application during the sustained current component markedly potentiated IBa. The results suggest that nifedipine binds with high affinity to the closed, available state of the Ca++ channels but they do not suggest binding to the open or inactivated states. The effect of BAY K 8644 is consistent with high affinity binding to the open or inactivated and to the closed, available states.
采用膜片钳技术的全细胞模式，研究了硝苯地平或BAY K 8644对从兔耳动脉分离的单个胶原酶和弹性蛋白酶处理的平滑肌细胞记录的钡电流的作用。硝苯地平（3 microM）使向-10 mV以上电位阶跃诱发的钡电流（IBa）降低。其特征为明显的“初始”阻滞，在电压钳制阶跃期间电流衰减速率增加，但如果每600 ms重复脉冲，则阻滞无增加。在持续电流成分期间（使用新的浓度跃变技术）快速细胞外施加硝苯地平（1 microM），发现在+20 mV时4秒内对IBa无影响，但在回到-60 mV的钳制电位10秒后，持续的IBa随后被消除。BAY K 8644（1 microM）在所有电位下均增加IBa，并且在持续电流成分期间快速施加时显著增强IBa。结果表明，硝苯地平与Ca++通道的关闭、可用状态具有高亲和力结合，但不表明与开放或失活状态结合。BAY K 8644的作用与与开放或失活状态以及关闭、可用状态的高亲和力结合一致。
