The effects of cerebral hypoxia on intracellular Ca^<2+> concentration

在缺氧的情况下，细胞内钙在细胞损伤中起着至关重要的作用。1)用钙荧光染料Quin2测定细胞内Cs~(2+)浓度，以及药物对其的影响(用大鼠脑突触体缺氧性模型)K~(2+)去极化通过电压依赖性钙通道的Ca~(2+)内流在缺氧组大于对照组。超过10微米的二氢吡啶类钙拮抗剂硝兰地平可抑制这种钙内流。2)挥发性麻醉剂对尼群地平与大鼠脑突触膜结合的影响氟烷、异氟烯和安氟烯等挥发性麻醉剂具有钙拮抗剂样活性(二氢吡啶类活性)，其作用与其麻醉作用有关。3)利多卡因诱发惊厥对大鼠脑内c-fos蛋白(c-fos)表达的影响。C-Fos是一种转录调节因子，由细胞内Ca~(2+)&gt；升高诱导。C-Fos的表达可作为脑代谢增强和细胞可塑性改变的良好指标。利多卡因惊厥后大鼠海马神经元c-Fos表达较弱，而戊四氮、海人酸、电惊厥等非麻醉性惊厥药物惊厥后c-Fos表达较强。但在利多卡丁惊厥后，杏仁核和梨状叶c-Fos的表达比海马区更强。这种表达被NMDA拮抗剂MK-801所依赖。

Intracellular calcium plays a crucial role on cell damage in the case of hypoxia. These experiments were perfomed in order to investigate following objects.1) Measurement of intracellular Cs^<2+> concentration using calcium fluorescent dye, Quin2, and the effects of drugs on it (using hyproxic mldel of rat cerebral synaptosomes)Ca^<2+> influx through voltage-dependent Ca channel by K^+ depolarization is greater in a hypoxic group than in a control group. More than 10 uM nitrandipine, a dihydropyridune-derivative Ca antagonist, depressed this Ca^<2+> influx. However, pentobarbital failed to inhibite Ca^<2+> influx through voltage-dependent Ca channel.2) Effects of volatile anesthetics on the [ ^3H]nitrendipine binding to rat cerebral synaptic membraneVolatile anesthetics such as halothane, isoflulene and enflulene had Ca antagonist-like activity (dyhydropyridine-derivative like activity) and their potencies were in order to their anesthetic potencies.3) Effects of lidocaine-induced convulsion on c-fos protein (c-Fos) expression in rat brainConvulsions cause cell damage due to a local ischemia. C-Fos is a transcriptional modulator and is induced by intracellular Ca^<2+> increase. C-Fos expression is suggested to be a good marker of the increase in cerebral metabolism and cellular plastic change. The c-Fos expression in nemrons of the hippocampus following lidocaine-induced convulsion was quite weak, while that following convulsions induced by non-anesthetic convulsant agents such as pentylenetetrazol, kainic acid, electroconvulsive shock was strong. Scatterd, however, more intense than that in hippocampal area, the exprossion of c-Fos was observed in amygdala and pyriform lobe following lidocatine-induced convulsion. This expression was deptessid by MK-801, a NMDA antagonist.