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

脑缺氧对细胞内Ca^<2>浓度的影响

• 批准号: 02670679
• 负责人: NAKAO Shin-ichi
• 金额: $ 1.41万
• 依托单位: Kyoto University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for General Scientific Research (C)
• 财政年份: 1990
• 资助国家: 日本
• 起止时间: 1990 至 1991
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-02670679/
• 关键词: Intracellular Calcium; Cerebral Hypoxia; Calcium Antagonist; Barbiturate; c-fos; NMDA receptor; Convulsion

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.

细胞内钙离子在细胞缺氧损伤中起着至关重要的作用。1）用钙荧光染料Quin 2测定细胞内Cs^<2+浓度及药物对其的影响（用大鼠脑突触体缺氧模型）缺氧组经K^+去极化的电压依赖性Ca通道的Ca^<2+内流大于对照组。超过10 μ M的尼群地平（一种二氢吡啶衍生物钙拮抗剂）可抑制这种Ca^2+内流。戊巴比妥不能阻断电压依赖性Ca ~（2+）通道的Ca ~（2+）内流。2）挥发性麻醉药对[^3 H]尼群地平与大鼠脑突触膜结合的影响异氟烯和恩氟烯具有钙拮抗剂样活性（二氢吡啶衍生物样活性）和它们的效力是为了它们的麻醉效力。3）利多卡因诱导的惊厥对c-大鼠脑内fos蛋白（c-Fos）表达惊厥可引起局部缺血引起细胞损伤。C-Fos是一种转录调节因子，由细胞内Ca^<2+>增加诱导。提示C-Fos表达是脑代谢增加和细胞可塑性改变的良好标志。利多卡因致惊厥后海马神经元c-Fos表达较弱，而戊四氮、海人酸、电休克致惊厥后海马神经元c-Fos表达较强。利多卡因惊厥后杏仁核和梨状叶c-Fos表达较强，但散在分布。这种表达被NMDA拮抗剂MK-801阻断。

项目成果

Shin-ichi Nakao: "Effects of lidocane-induced convulsion on the c-fos protein (c-Fos) expression in rat brain" Acta Anaesthesiol Scand.

Shin-ichi Nakao：“利多卡因诱导的惊厥对大鼠脑中 c-fos 蛋白 (c-Fos) 表达的影响”Acta Anaesthesiol Scand。