突触前α7烟碱受体对海马神经元兴奋性突触传递的调控

采用盲法膜片钳技术观察突触前烟碱受体(nicotinic acetylcholinel receptors,nAChRs)对海马脑片CAl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(dimethylphenyl—piperazinium iodide,DMPP)不能在CAl区锥体神经元上诱发出烟碱电流。DMPP对CAl区锥体神经元自发兴奋性突触后电流(spontaneous excitatory postsynaptic current,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(miniature excitatory postsynaptic current,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-β-刺桐丁所阻断,但可被α-银环蛇毒素阻断。上述结果提示,海马脑片CAl区锥体神经元兴奋性突触前nAChRs含有对α-银环蛇毒素敏感的胡亚单位,其激活可增强海马CAl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。

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

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 dihydro-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.