短暂脑缺血对大鼠海马脑区锥体神经元外向整流氯通道功能的影响(1)
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摘要：目的 研究短暂前脑缺血对大鼠海马CA1和CA3脑区锥体神经元外向整流氯通道功能的影响。方法 采用膜片钳全细胞技术，在成年大鼠海马脑区锥体神经元上记录到可以被氯通道阻断剂 DIDS阻断，具有外向整流特性的氯通道。结果 15 min前脑缺血再灌注6 h和24 h后，海马CA1区锥体神经元氯通道电流持续性增强，而CA3区锥体神经元活动无明显改变。结论 氯通道功能增强可能参与海马CA1区锥体神经元在脑缺血后的迟发性死亡过程，并且为治疗缺血性脑损伤提供了新的手段。
关键词：外向整流氯通道；膜片钳；脑缺血；神经元死亡；海马
中图分类号：R743 R255.2 文献标识码：A 文章编号：16721349(2012)02020903
The Influence of Transient Forebrain Ischemia on the Outwardly Rectifying Chloride Channels in Pyramidal Neurons of Rat Hippocampus
Li Jianguo,Liu Naihong,Chen Jianming // Shanxi Medical University(Taiyuan 030001)
Abstract:Objective To investigate the effect of transient forebrain ischemia on the outwardly rectifying chloride channels(ORCC) in pyramidal neurons of rat hippocampus.Methods The ORCC currents were studied by wholecell patchclamp technique,which one kind of chloride channel blocker 4,4’diisothiocyanatostilbene2,2’disulfonic acid (DIDS) could be blocked.Results After 6 hours and 24 hours reperfusion after 15 min forebrain ischemia,ORCC activity in CA1 and CA3 pyramidal neurons of rat hippocampus were examined.ORCC activity was persistently unregulated in vulnerable CA1 neurons after ischemic insult,whereas no change occurred in invulnerable CA3 neurons.Conclusion The present results suggest that the enhanced activities of ORCC may contribute to the selective neuronal damage in vulnerable CA1 region after transient forebrain ischemia,and ORCC would be a therapeutic target against the ischemiainduced neuronal damage.
Key words:outwardly rectifying chloride channel;patchclamp;ischemia;brain neuronal death;hippocampus
海马CA1区的锥体神经元对于缺血损伤特别敏感，并且在短暂前脑缺血后呈现迟发性神经元凋亡，而CA3和齿状回神经细胞不受此影响。目前对这种选择性细胞死亡的机制仍不清楚[1]。研究表明，细胞凋亡参与了脑缺血后神经元的死亡过程[2]，而且钾通道和氯通道等离子通道参与细胞的凋亡过程[3，4]。
目前，除了三类已知基因表达的氯离子通道，如配体门控氯通道(甘氨酸受体和GABA受体)、ClC氯通道( ClC1 ~ ClC7, ClCK1 和 ClCK2)和囊性纤维变性调节因子氯通道(CFTR)，细胞膜上还分布着一种功能表达的氯通道，即外向整流氯离子通道(outwardly rectifying chloride channels)。这是一种中等电导大小，具有外向整流特性的氯通道。虽然其分子结构仍然不清楚，但是大量的研究发现，外向整流氯离子通道参与了细胞的凋亡性死亡过程[4]，细胞死亡的程度能够被氯通道阻断剂所减缓[5]。因此，认为外向整流氯离子通道可能参与了海马CA1区锥体神经元在缺血后出现的迟发性死亡过程 ......
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