Leybaert L, De Ley G, de Hemptinne A
Laboratorium voor Normale en Pathologische Fysiologie, Universiteit Gent, Belgium.
Naunyn Schmiedebergs Arch Pharmacol. 1993 Sep;348(3):269-74. doi: 10.1007/BF00169155.
The effect of the calcium entry blocker flunarizine on a high-potassium induced increase of intracellular free calcium was studied. The experiments were done with neurons isolated from rat dorsal root ganglia and loaded with the calcium-sensitive dye fura-2. The increase of calcium induced by 60 mmol/l potassium was abolished after removal of extracellular calcium, was reversibly reduced by 50 mumol/l cadmium (76% inhibition), 50 mumol/l nickel (25% inhibition) and 10 mumol/l nifedipine (18% inhibition), and reversibly increased after removal of extracellular sodium (26% increase). The potassium induced increase of intracellular calcium is, therefore, mediated by transmembrane calcium influx, probably to a large extent through cadmium-sensitive calcium channels. Flunarizine (5 min incubation followed 1 min wash-out) reduced the amplitude of the high-potassium induced calcium increase in a dose-dependent manner (Kd = 370 +/- 100 nmol/l; mean +/- SEM; n = 8), causing complete inhibition at a concentration of 10 mumol/l in the majority of cells. Flunarizine (> or = 1 mumol/l) caused a reversible increase of the resting level of intracellular calcium in some cells, an effect which disappeared in the absence of extracellular calcium. The drug (1 mumol/l had no influence on the time course of recovery of intracellular calcium subsequent to a rise induced by high-potassium or by the calcium ionophore A23,187. It is concluded that flunarizine acts as an inhibitor of depolarization-mediated calcium influx. At a concentration of 1 mumol/l, the drug presumably has no effect on cellular calcium extrusion and/or sequestration mechanisms.
研究了钙通道阻滞剂氟桂利嗪对高钾诱导的细胞内游离钙增加的影响。实验采用从大鼠背根神经节分离的神经元，并加载钙敏染料fura-2进行。去除细胞外钙后，60 mmol/l钾诱导的钙增加被消除，50 μmol/l镉（抑制76%）、50 μmol/l镍（抑制25%）和10 μmol/l硝苯地平（抑制18%）可使其可逆性降低，去除细胞外钠后则可逆性增加（增加26%）。因此，钾诱导的细胞内钙增加是由跨膜钙内流介导的，可能在很大程度上通过对镉敏感的钙通道。氟桂利嗪（孵育5分钟后冲洗1分钟）以剂量依赖方式降低高钾诱导的钙增加幅度（Kd = 370 ± 100 nmol/l；平均值 ± 标准误；n = 8），在大多数细胞中，10 μmol/l浓度时可完全抑制。氟桂利嗪（≥1 μmol/l）在一些细胞中可使细胞内钙的静息水平可逆性增加，在无细胞外钙时该效应消失。该药物（1 μmol/l）对高钾或钙离子载体A23,187诱导升高后细胞内钙恢复的时间进程无影响。结论是氟桂利嗪作为去极化介导的钙内流抑制剂起作用。在1 μmol/l浓度时，该药物可能对细胞钙外排和/或螯合机制无影响。
