Effects of dynorphin on rat entopeduncular nucleus neurons in vitro.
Effects of dynorphin on rat entopeduncular nucleus neurons in vitro.
复制标题
强啡肽对体外大鼠内脚核神经元的影响。
DOI：
10.1016/s0306-4522(02)00355-x
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发表时间：
2002
期刊：
影响因子：
3.3
通讯作者：
Kita,H
中科院分区：
文献类型：
--
作者：
Ogura,M;Kita,H
内脚核 (EP) 接收密集的新纹状体传入轴突，其中除了 GABA 和 P 物质外，还含有强啡肽（DYN，一种内源性 κ 受体激动剂）。为了检查 DYN 在 EP 中的作用，在大鼠脑切片制剂中进行了全细胞记录。根据生理和形态特征，记录的所有神经元与先前研究中描述的 I 型 EP 神经元相似。 κ 受体激动剂强啡肽 A (1-13) (DYN13) 使约四分之一的 EP 神经元超极化并降低了输入电阻。超极化是由于钾电导增加所致，因为 DYN13 应用前后获得的电流-电压关系曲线在钾平衡电位处交叉。在人工脑脊液中存在谷氨酸阻断剂 1,2,3,4-四氢-6-硝基-2,3-二氧代-苯并[f]喹喔啉-7-磺酰胺和 3-(2-羧基哌嗪-4-基)-丙基-1-膦酸时，苍白球的刺激在 EP 中引起荷包牡丹碱敏感的多组分 GABA 能反应神经元。 DYN13的应用同样降低了短潜伏期反应（可能由苍白球-EP轴突引起）和中潜伏期反应（可能由纹状体-EP轴突引起）的幅度。通过浴敷非选择性阿片拮抗剂纳洛酮或 κ-阿片受体选择性拮抗剂去甲-联二托菲明二盐酸盐 (nor-BNI) 可逆转这些效应，但 ∂-拮抗剂纳曲吲哚或 μ-拮抗剂 D-Phe-Cys-Tyr-D-Trp-Orn-Thr-Pen-Thr-NH2 则不能逆转这些效应。 DYN13 还降低了河豚毒素不敏感的微型抑制性突触后电位 (mIPSP) 的频率，而不改变其幅度分布。 mIPSP 频率的降低在洗涤后是可逆的，并且也被 Nor-BNI 完全阻断。目前对 EP 的研究结果表明，从纹状体轴突释放的 DYN 可能对这些靶核产生至少三种不同的影响。首先，DYN 可能在其终止位点对纹状体 GABA 能输出提供负反馈调节。其次，从纹状体末端释放的 DYN 可能扩散到苍白球末端，调节其 GABA 释放。第三，DYN可能对EP神经元产生直接抑制作用。因此，从纹状体轴突释放的 DYN 可能通过减少 GABA 能传递以及超极化突触后膜来控制 EP 神经元的活动。
The entopeduncular nucleus (EP) receives dense neostriatal afferent axons that contain dynorphin (DYN, an endogenous κ-receptor agonist), in addition to GABA and substance P. To examine the role of DYN in the EP, whole-cell recordings were performed in rat brain slice preparations. Based on the physiological and morphological characteristics, all the neurons recorded were similar to the Type-I EP neuron described in a previous study. The κ-receptor agonist dynorphin A (1-13) (DYN13) hyperpolarized and decreased the input resistance of approximately one-quarter of the EP neurons examined. The hyperpolarization was due to an increase in potassium conductance since current–voltage relationship curves obtained before and after DYN13 application crossed at the potassium equilibrium potential. In the presence of the glutamate blocker 1,2,3,4-tetrahydro-6-nitro-2,3-dioxo-benzo[f]quinoxaline-7-sulfonamide and 3-(2-carboxypiperzin-4-yl)-propyl-1-phosphonic acid in artificial cerebrospinal fluid, stimulation of the globus pallidus evoked bicuculline-sensitive multi-component GABAergic responses in EP neurons. Application of DYN13 equally reduced the amplitudes of the short-latency response, conceivably evoked by pallido-EP axons, and the medium-latency response, conceivably evoked by striato-EP axons. These effects were reversed by bath application of a non-selective opioid antagonist naloxone or by a κ-opioid receptor-selective antagonist nor-binaltorphimine dihydrochloride (nor-BNI), but not by the ∂-antagonist naltrindole or the μ-antagonist D-Phe-Cys-Tyr-D-Trp-Orn-Thr-Pen-Thr-NH2. DYN13 also reduced the frequency of tetrodotoxin-insensitive miniature-inhibitory postsynaptic potential (mIPSPs) without changing their amplitude distributions. The decrease of the frequency of mIPSPs was reversible upon washing and was also completely blocked by nor-BNI. The results of the present study on the EP indicated that DYN released from striatal axons might exert at least three different effects on these target nuclei. Firstly, DYN might provide negative feedback regulation of striatal GABAergic outputs at their termination sites. Secondly, DYN released from the striatal terminals might diffuse to the pallidal terminals, regulating their GABA release. Thirdly, DYN might exert a direct inhibition of EP neurons. Thus, DYN released from striatal axons might control the activity of EP neurons by reducing the GABAergic transmission and also by hyperpolarizing postsynaptic membrane.