Nakazawa K, Inoue K, Ohara-Imaizumi M, Fujimori K, Takanaka A
Division of Pharmacology, National Institute of Hygienic Sciences, Tokyo, Japan.
Brain Res. 1991 Jul 5;553(1):44-50. doi: 10.1016/0006-8993(91)90228-n.
The effects of diazepam on voltage-gated Ca channels were studied in PC12 pheochromocytoma cells using whole-cell voltage-clamp techniques. An inward current activated by a depolarizing voltage step to +10 mV from a holding potential of -60 mV in 10.8 mM Ba was larger than that activated in 10.8 mM Ca. The Ba current was completely blocked by a low concentration of Cd (30 microM) and was also sensitive to nicardipine (100 nM to 10 microM). Diazepam (1-100 microM) inhibited the Ba current in a concentration-dependent manner. Neither diazepam nor nicardipine affected the current-voltage relationship or the dependence on holding potentials of the Ba current. Both slightly accelerated the inactivation time course of the Ba current. When diazepam was applied to the cells in combination with nicardipine, the observed inhibition agreed with a value predicted assuming independent blockade by diazepam and by nicardipine. These results suggest that diazepam inhibits Ca channels in a manner similar to nicardipine, but that the binding sites for diazepam are different from those for nicardipine.
采用全细胞膜片钳技术，在PC12嗜铬细胞瘤细胞中研究了地西泮对电压门控钙通道的影响。在10.8 mM Ba中，从 -60 mV的钳制电位去极化至 +10 mV所激活的内向电流大于在10.8 mM Ca中激活的电流。Ba电流被低浓度的Cd（30 microM）完全阻断，并且对尼卡地平（100 nM至10 microM）也敏感。地西泮（1 - 100 microM）以浓度依赖的方式抑制Ba电流。地西泮和尼卡地平均不影响Ba电流的电流 - 电压关系或对钳制电位的依赖性。二者均略微加速了Ba电流的失活过程。当将地西泮与尼卡地平联合应用于细胞时，观察到的抑制作用与假设地西泮和尼卡地平独立阻断时预测的值一致。这些结果表明，地西泮以类似于尼卡地平的方式抑制钙通道，但地西泮的结合位点与尼卡地平的不同。
