Mulle C, Vidal C, Benoit P, Changeux J P
UA CNRS D1284 "Neurobiologie Moléculaire," Département des Biotechnologies, Institut Pasteur, Paris.
J Neurosci. 1991 Aug;11(8):2588-97. doi: 10.1523/JNEUROSCI.11-08-02588.1991.
Neuronal nicotinic ACh receptors (nAChRs) are present in the rat medial habenula (MHB) and interpeduncular nucleus (IPN), two brain regions connected through the fasciculus retroflexus (FR). The goal of the present study was to compare the electrophysiological and pharmacological characteristics of nAChRs located at pre- and postsynaptic sites within the MHB-IPN system. nAChRs located on the soma of IPN neurons were studied using patch-clamp techniques and a preparation of acutely isolated neurons. Whole-cell currents evoked by Ach and nicotine showed an intense rectification at positive membrane potentials. nAChR channels were relatively nonselective for cations, had a unitary conductance of 35 pS, and were activated by several nicotinic agonists with the following rank order: cytisine greater than ACh greater than nicotine greater than dimethylphenylpiperazinium (DMPP). They were blocked by mecamylamine, hexamethonium, curare, and dihydro-beta-erythroidine (DHBE), but were insensitive to alpha-bungarotoxin and neuronal bungarotoxin. In contrast, nAChRs recorded on the soma of MHB neurons under equivalent experimental conditions exhibited different characteristics for single-channel conductance and agonist and antagonist sensitivity. The pharmacological properties of presynaptic nAChRs in the IPN were analyzed in a rat brain slice preparation. Stimulation of the FR produced a presynaptic afferent volley recorded in the rostral subnucleus of the IPN. Nicotinic agonists decreased the amplitude of the afferent volley with different efficacies: nicotine greater than cytisine greater than ACh greater than DMPP. The action of nicotine was insensitive to alpha-bungarotoxin and to neuronal bungarotoxin, but was blocked by mecamylamine, hexamethonium, curare, and DHBE, with IC50 values different from those reported for IPN postsynaptic nAChRs. This study thus demonstrates the functional diversity of nAChRs in the rat CNS.
神经元烟碱型乙酰胆碱受体（nAChRs）存在于大鼠内侧缰核（MHB）和脚间核（IPN）中，这两个脑区通过缰核脚间束（FR）相连。本研究的目的是比较位于MHB - IPN系统突触前和突触后位点的nAChRs的电生理和药理学特性。使用膜片钳技术和急性分离神经元的制备方法，研究了位于IPN神经元胞体上的nAChRs。乙酰胆碱（Ach）和尼古丁诱发的全细胞电流在正膜电位时表现出强烈的整流作用。nAChR通道对阳离子相对非选择性，单通道电导为35 pS，并被几种烟碱型激动剂激活，其顺序如下：金雀花碱大于Ach大于尼古丁大于二甲基苯基哌嗪（DMPP）。它们被美加明、六甲铵、箭毒和二氢β - 刺桐碱（DHBE）阻断，但对α - 银环蛇毒素和神经元型银环蛇毒素不敏感。相比之下，在相同实验条件下记录到的MHB神经元胞体上的nAChRs在单通道电导以及激动剂和拮抗剂敏感性方面表现出不同的特性。在大鼠脑片制备中分析了IPN中突触前nAChRs的药理学特性。刺激FR在IPN的嘴侧亚核中记录到突触前传入冲动。烟碱型激动剂以不同的效力降低传入冲动的幅度：尼古丁大于金雀花碱大于Ach大于DMPP。尼古丁的作用对α - 银环蛇毒素和神经元型银环蛇毒素不敏感，但被美加明、六甲铵、箭毒和DHBE阻断，其半数抑制浓度（IC50）值与报道的IPN突触后nAChRs不同。因此，本研究证明了大鼠中枢神经系统中nAChRs的功能多样性。
