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突触前#alpha#7烟碱受体对海马神经元兴奋性突触传递的调控

刘振伟, 杨胜, 张永祥, 刘传缋

军事医学科学院毒物药物研究所.北京 100850

摘要

采用盲法膜片钳技术观察突触前烟碱受体(nAChRs)对海马脑片CA1区锥体神经元兴奋性突触传递的调控作用。结果显示,nAChRs激动剂碘化二甲基苯基哌嗪(DMPP)不能在CA1区锥体神经元上诱发出烟碱电流。DMPP对CA1区锥体神经自发兴奋性突触后电流(sEPSC)具有明显的增频和增幅作用,并呈现明显的浓度依赖关系。DMPP对微小兴奋性突触后电流(mEPSC)具有增频作用,但不具有增幅作用。上述DMPP增强突触传递的作用不能被nAChRs拮抗剂美加明、六烃季铵和双氢-#beta#-刺桐丁所阻断,但可被#alpha#-银环蛇毒素阻断。上述结果提示,海马脑片CA1区锥体神经元兴奋性突触前nAChRs含有对#alpha#-银环蛇毒素敏感的#alpha#7亚单位,其激活可增强海马CA2区锥体神经元突触前递质谷氨酸的释放,从而对兴奋性突触传递发挥调控作用。

关键词： 烟碱受体; 海马脑片; 突触传递; 谷氨酸; 碘化二甲基苯基哌嗪

Presynaptic alpha-7 nicotinic acetylcholine receptors modulate excitatory synaptic transmission in hippocampal neurons

Liu Zhenwei, Yang Sheng, Zhang Yongxiang, Liu Chuanhui

Beijing Institute of Pharmacology and Toxicology.Beijing 100850

Abstract

The effects of presynaptic nicotinic acetylcholine receptors (nAChRs) on excitatory synaptic transmission in CA1 pyramidal neurons of the rat hippocampus were examined by blind whole-cell patch clamp recording from hippocampal slice preparations. Local application of the nAChRs agonist dimethylphenyl-piperazinium iodide (DMPP) did not induce a postsynaptic current response in CA1 pyramidal cells. However, DMPP enhanced the frequency and amplitude of spontaneous excitatory postsynaptic current (sEPSC) in these cells in a dose-dependent manner. This enhancement was blocked by the selective nicotinic #alpha#-7 receptor antagonist #alpha#-bungarotoxin, but not by the antagonist mecamylamine, hexamethonium or dihyhro-#beta#-erythroidine. The frequency of miniature excitatory postsynaptic current (mEPSC) in CA1 pyramidal neurons was also increased by application of DMPP, indicating a presynaptic site of action of the agonist. Taken together, these results suggest that activation of presynaptic nAChRs in CA1 pyramidal neurons, which contain #alpha#-7 subunits, potentiates presynaptic glutamate release and consequently modulate excitatory synaptic transmission in the hippocampus.

Key words: Nicotinic;Acetylcholine receptors （ nAChRs）;Hippocampal slice synaptic transmission;Glutamate （ Glu）;Dimethylphenyl-piperazinium iodide （DMPP）

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引用本文：

刘振伟, 杨胜, 张永祥, 刘传缋. 突触前#alpha#7烟碱受体对海马神经元兴奋性突触传递的调控[J]. 生理学报 2003; 55 (6): .

Liu Zhenwei, Yang Sheng, Zhang Yongxiang, Liu Chuanhui. Presynaptic alpha-7 nicotinic acetylcholine receptors modulate excitatory synaptic transmission in hippocampal neurons. Acta Physiol Sin 2003; 55 (6): (in Chinese with English abstract).