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Investigation of mechanism of central nervous system disorder due to chlorinated

氯化物引起中枢神经系统紊乱的机制研究

基本信息

批准号：
12470085
负责人：
HOBARA Tatsuya
金额：
$ 7.62万
依托单位：
Yamaguchi University
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (B)
财政年份：
2000
资助国家：
日本
起止时间：
2000 至 2002
项目状态：
已结题

项目摘要

Calcium ion in neurons plays an important role in development of action potential, release of neurotransmitter and intracellular signaling with synapse formation and physiological functions. Intracellular calcium ion is derived from either influx from the extracellular fluid through the membrane calcium channels o* release out of the intracellular calcium store sites. Organic solvents used in the field of manufacturing and service industry cause clinical symptoms related to depression of central nervous system function.We have dissociated dorsal root ganglion neurons from neonatal rat to measure the voltage-dependent calcium current in a whole cell mode of the patch clump. Trichloroethane and trichloroethyene decreased the calcium current. And intervals of the action potential in the current clump mode were shortened. We also found the involvement of other voltage-gated cation channels. Next we investigated the change of intracellular calcium ion concentration released from the intracelular calcium stores with a fluo-indicator Fluo-3. We used in this experiments caffeine which modifies ryanodine receptor of intracellular calcium store, and ATP which stimulates the nucleotide receptor of the DRG neurons. Caffeine induced the increasing of the intracellular calcium level, and trichloroethylene inhibited the increasing. The rise of the intracellular calcium level was also impaired with 1-bromopropane and 2-bromopropane. We also studied aortic smooth muscle and got the same results. These studies suggested that some of organic solvents could act on both the plasma membrane of the neurons and cytoplasmic organelles in entering though the plasma membrane and finally modify the action potential and neurotransmitter release.

神经元中的钙离子与突触的形成和生理功能有关，在动作电位的形成、神经递质的释放和细胞内信号转导等方面发挥着重要作用。细胞内钙离子是通过膜钙通道从细胞外液流入，或从细胞内钙储存部位释放出来的。有机溶剂在制造业和服务业领域的应用会导致与中枢神经系统功能抑制相关的临床症状。我们分离了新生大鼠背根神经节神经元，以全细胞模式测量了膜片簇的电压依赖性钙电流。三氯乙烷和三氯乙烯使钙电流降低。并且缩短了当前丛集模式下的动作电位间期。我们还发现了其他电压门控阳离子通道的参与。接下来，我们用荧光指示剂Fluo-3研究了细胞内钙库释放的钙离子浓度的变化。在这个实验中，我们使用了咖啡因和三磷酸腺苷，咖啡因可以改变细胞内钙储存的兰尼定受体，三磷酸腺苷可以刺激背根神经节神经元的核苷酸受体。咖啡因可引起细胞内钙离子浓度升高，三氯乙烯对此有抑制作用。1-溴丙烷和2-溴丙烷对细胞内钙离子浓度的升高也有抑制作用。我们也对主动脉平滑肌进行了研究，得到了相同的结果。这些研究表明，某些有机溶剂可通过质膜同时作用于神经元的质膜和胞质细胞器，最终改变动作电位和神经递质的释放。