Glial cell line-derived neurotrophic factor acutely modulates the excitability of rat small-diameter trigeminal ganglion neurons innervating facial skin
Glial cell line-derived neurotrophic factor acutely modulates the excitability of rat small-diameter trigeminal ganglion neurons innervating facial skin
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DOI：
10.1016/j.bbi.2009.08.002
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发表时间：
2010-01-01
影响因子：
15.1
通讯作者：
Matsumoto, Shigeji
中科院分区：
文献类型：
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作者：
Takeda, Mamoru;Kitagawa, Junichi;Matsumoto, Shigeji
胶质细胞系来源的神经营养因子（GDNF）在成人感觉神经元功能中起着重要作用。然而，GDNF对初级感觉神经元兴奋性的急性影响仍有待阐明。本研究的目的是通过穿孔贴片夹持、逆行标记和免疫组织化学技术，研究GDNF是否能急性调节控制面部皮肤的成年大鼠三叉神经节（TRG）神经元的兴奋性。采用氟金（FG）逆行标记法对支配面部皮肤的TRG神经元进行鉴定。fg标记了中小直径GDNF免疫反应性TRG神经元，这些神经元大多数也表达GDNF家族受体α -1 （GFR α -1）。在全细胞电压钳模式下，GDNF应用显著抑制了大多数分离的fg标记的小直径TRG神经元的电压门控K+瞬态（I-A）和持续（I-K）电流。这种作用是浓度依赖性的，并通过酪氨酸激酶抑制剂K252b的联合应用而消除。在电流箝位条件下，GDNF的应用显著增加了去极化脉冲中的重复放电。GDNF的应用也增加了动作电位复极化期的持续时间，减少了动作电位去极化期的持续时间，而K252b的共同应用也消除了这些特征效应。这些结果表明，急性应用GDNF可通过激活GDNF诱导的细胞内信号通路，增强支配面部皮肤的成年大鼠小直径TRG神经元的神经元兴奋性。因此，我们得出结论，从TRG神经元体和/或神经末梢局部释放GDNF可能调节正常的感觉功能，包括伤害感觉。(C) 2009爱思唯尔公司版权所有。
Glial cell line-derived neurotrophic factor (GDNF) plays an important role in adult sensory neuron function. However, the acute effects of GDNF on primary sensory neuron excitability remain to be elucidated. The aim of the present study was to investigate whether GDNF acutely modulates the excitability of adult rat trigeminal ganglion (TRG) neurons that innervate the facial skin by using perforated-patch clamping, retrograde-labeling and immunohistochemistry techniques. Fluorogold (FG) retrograde labeling was used to identify the TRG neurons innervating the facial skin. The FG-labeled small- and medium-diameter GDNF immunoreactive TRG neurons, and most of these neurons also expressed the GDNF family receptor alpha-1 (GFR alpha-1). In whole-cell voltage-clamp mode, GDNF application significantly inhibited voltage-gated K+ transient (I-A) and sustained (I-K) currents in most dissociated FG-labeled small-diameter TRG neurons. This effect was concentration-dependent and was abolished by co-application of the protein tyrosine kinase inhibitor, K252b. Under current-clamp conditions, the repetitive firing during a depolarizing pulse were significantly increased by GDNF application. GDNF application also increased the duration of the repolarization phase and decreased the duration of the depolarization phase of the action potential, and these characteristic effects were also abolished by co-application of K252b. These results suggest that acute application of GDNF enhances the neuronal excitability of adult rat small-diameter TRG neurons innervating the facial skin, via activation of GDNF-induced intracellular signaling pathway. We therefore conclude that a local release of GDNF from TRG neuronal soma and/or nerve terminals may regulate normal sensory function, including nociception. (C) 2009 Elsevier Inc. All rights reserved.