Léna C, Changeux J P, Mulle C
URA CNRS D1284, Département des Biotechnologies, Institut Pasteur, Paris, France.
J Neurosci. 1993 Jun;13(6):2680-8. doi: 10.1523/JNEUROSCI.13-06-02680.1993.
Presynaptic nicotinic ACh receptors (nAChRs) are abundant in the nervous system, where they are thought to regulate the release of various neurotransmitters. Whole-cell recordings performed on rat interpeduncular nucleus neurons using the thin-slice technique showed that nicotine dramatically increased the frequency of postsynaptic GABAergic currents. This effect was observed at low micromolar concentration of agonist; it was mimicked by cytisine, dimethylphenylpiperazinium, and ACh in the presence of eserine. It was blocked by hexamethonium, dihydro-beta-erythroidine, and mecamylamine. The presynaptic action was suppressed in the presence of TTX. A comparable effect of nicotine was found using a preparation of acutely isolated neurons that had retained synaptic terminals attached to their cell body as evidenced by immunoreactivity to synaptophysin and presence of spontaneous GABAergic and glutamatergic synaptic activity. Nicotinic agonists increased the frequency of GABAergic postsynaptic currents, an effect blocked by curare and mecamylamine. This action was also suppressed in the presence of TTX. These data suggest the presence of nAChRs at a preterminal level on axons of intrinsic GABAergic neurons. We propose that, in contrast to presynaptic nAChRs, activation of these "preterminal" nAChRs can trigger a spike discharge and thus have a generalized action on the GABAergic afferent.
突触前烟碱型乙酰胆碱受体（nAChRs）在神经系统中大量存在，人们认为它们可调节多种神经递质的释放。使用薄片技术对大鼠脚间核神经元进行的全细胞记录显示，尼古丁显著增加了突触后GABA能电流的频率。在低微摩尔浓度的激动剂作用下即可观察到这种效应；在毒扁豆碱存在的情况下，金雀花碱、二甲基苯基哌嗪鎓和乙酰胆碱可模拟该效应。它可被六甲铵、二氢β-刺桐啶和美加明阻断。在河豚毒素（TTX）存在的情况下，突触前作用受到抑制。使用急性分离的神经元制备物也发现了尼古丁的类似效应，这些神经元保留了附着在其细胞体上的突触终末，这可通过对突触素的免疫反应性以及自发的GABA能和谷氨酸能突触活动得到证明。烟碱型激动剂增加了GABA能突触后电流的频率，这一效应可被箭毒和美加明阻断。在TTX存在的情况下，这一作用也受到抑制。这些数据表明，在内在GABA能神经元轴突的终末前水平存在nAChRs。我们提出，与突触前nAChRs不同，这些“终末前”nAChRs的激活可触发动作电位发放，从而对GABA能传入产生广泛作用。
