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Effects of the P/Q-type calcium channel of ischemic neuronal damage characterized by neuronal functional images

以神经元功能图像为特征的 P/Q 型钙通道对缺血性神经元损伤的影响

基本信息

批准号：
18591692
负责人：
FUJIWARA Naoshi
金额：
$ 2.02万
依托单位：
Niigata University
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (C)
财政年份：
2006
资助国家：
日本
起止时间：
2006 至 2007
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-18591692/
关键词：
cerebral cortex hippocampus voltage-sensitive dye intracellular calcium P Q-type calcium channel ω-agatoxin IVA GABA_A receptor thiamylal ω-アガトキシンチアミラール

项目摘要

This study aims to clarify the relationship between the P/Q-type calcium channel or the GABAA receptor and ischemic neuronal damage. Effects of a P/Q-type calcium channel blocker and GABAA receptor modulator on ischemic neuronal damage were investigated by means of spatio-temporal analyses of excitation propagation and intracellular calcium changes in cortical and hippocampal slices of the mouse brain.(1) Electrical stimulation to layer V of a cortical slice evoked transient depolarization in the vicinity of stimulated site. Then this excitatory response propagated to layers II-III and widely expanded in these layers. Intracellular calcium level was also elevated in layers II-III. The excitation propagation and calcium elevation were inhibited by a P/Q-type calcium channel blocker ω-agatoxin IVA(50 nmol/l). These results suggest that the P/Q-type calcium channel plays an important role in excitation propagation in the cerebral cortex.(2) Excitation propagation in both cortical and hippocampal slices was preserved in an oxygenated Krebs solution over 20 hours after their preparation. But, in slices exposed to transient in vitro ischemia (oxygen-glucose deprivation from a bathing medium) for 5 min, excitation propagation almost disappeared 18-20 hours after the ischemic exposure. This neuronal dysfunction also occurred in the slices exposed to In vitro ischemia in the presence of w-agatoxin IVA (200 nmol/l), suggesting that the neuronal dysfunction cannot be prevented by blocking the P/Q-type calcium channel.(3) A GABA_A receptor modulator thiamylal (200 μmol/l) inhibited the excitation propagation in cortical slices. Excitation propagation was partially preserved in both cortical and hippocampal slices after the exposure to transient in vitro ischemia in the presence of thiamylal. The result suggests that the enhancement of GABA_A receptor activity protects the ischemic neuronal dysfunction in the cortex and hippocampus.

本研究旨在阐明P/Q型钙通道或GABAA受体与缺血性神经元损伤的关系。本文通过对小鼠大脑皮层和海马脑片兴奋传播和细胞内钙变化的时空分析，研究了P/Q型钙通道阻滞剂和GABAA受体调节剂对缺血性神经元损伤的影响。(1)电刺激皮层切片的V层诱发刺激部位附近的瞬时去极化。然后，这种兴奋性反应传播到II-III层，并在这些层中广泛扩展。细胞内钙水平也升高，在第二-第三层。P/Q型钙通道阻断剂ω-agatoxin IVA（50 nmol/l）可抑制兴奋传播和钙升高。这些结果表明，P/Q型钙通道在大脑皮层兴奋传播中起着重要作用。(2)皮质和海马切片中的兴奋传播在其制备后20小时内保存在氧合的Krebs溶液中。但是，在暴露于短暂的体外缺血（从浴介质中剥夺氧-葡萄糖）5分钟的切片中，在缺血暴露后18-20小时，兴奋传播几乎消失。这种神经元功能障碍也发生在暴露于W-agatoxin IVA（200 nmol/l）存在下的体外缺血的切片中，表明神经元功能障碍不能通过阻断P/Q-型钙通道来预防。(3)GABA_A受体调节剂硫戊醛（200 μmol/l）抑制皮层脑片兴奋传递。兴奋传播被部分保存在皮质和海马切片暴露后，短暂的体外缺血存在的甲硫氨酸。提示GABA_A受体活性的增强对缺血性皮层和海马神经元功能障碍具有保护作用。