Expression of auxiliary β subunits of sodium channels in primary afferent neurons and the effect of nerve injury
Expression of auxiliary β subunits of sodium channels in primary afferent neurons and the effect of nerve injury
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DOI：
10.1016/s0306-4522(03)00432-9
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发表时间：
2003-01-01
期刊：
影响因子：
3.3
通讯作者：
Noguchi, K
中科院分区：
文献类型：
--
作者：
Takahashi, N;Kikuchi, S;Noguchi, K
多个电压门控钠通道是细胞兴奋性的主要介质。它们是由成孔α亚基和辅助β亚基组成的多聚体。虽然离子渗透性和电压感应主要由α亚基决定，但β亚基是钠通道功能的重要调节剂。本研究的目的是评估轴突切断对背根神经节（DRG）中β亚基（β（1）、β（2）和β（3））表达以及Na（v）1.3和β（3）亚基共表达的影响。我们采用大鼠坐骨神经横断模型和保留神经损伤（SNI）模型。在逆转录聚合酶链反应分析中，轴突切断后3天，对侧和同侧DRG之间的β（1）和β（2）mRNA无显著差异。与对侧相比，切断后3d，同侧DRG中β 3 mRNA的表达显著增加。在原位杂交组织化学中，β（3）mRNA主要表达于中型至大型神经元，而β（2）mRNA表达于小型至大型神经元。轴突切断后3d，对侧和同侧背根神经节β 1和β 2 mRNA无显著差异。相反，β（3）mRNA主要在小神经元中表达，偶尔在中到大尺寸神经元中表达，并且同侧DRG中小c型神经元中的β（3）mRNA表达显著高于对侧DRG。我们用双标记法检测了轴突切断后DRG神经元中β 3 mRNA与α亚基之一Na（v）1.3-ir的表达。我们发现在受损的DRG神经元中有很高比例的共表达：83.6+/-2.8%的表达β 3 mRNA的神经元被Na（v）1.3-ir标记; 70.1+/-3.1%的Na（v）1.3-ir神经元表达β 3 mRNA。我们还检测了SNI模型（一种神经病理性疼痛模型）中DRG神经元中β（3）mRNA的表达。我们使用激活转录因子3来鉴定轴突切断的神经元，发现在神经病理性疼痛模型中，β（3）mRNA的上调主要发生在轴突切断的神经元中。这些数据有力地表明，β（3）的表达在受损的DRG神经元轴突切断后可能是一个重要的病理机制，神经损伤后疼痛的初级感觉神经元。(C)2003年IBRO。由爱思唯尔有限公司出版。保留所有权利。
Multiple voltage-gated sodium channels are the primary mediators of cell excitability. They are multimers that consist of the pore-forming alpha subunit and auxiliary beta subunits. Although ion permeability and voltage sensing are primarily determined by the alpha subunit, beta subunits are important modulators of sodium channel function. The purpose of this study was to assess the effect of axotomy on the expression of beta subunits (beta(1), beta(2) and beta(3)) and coexpression of Na(v)1.3 and beta(3) subunits in the dorsal root ganglion (DRG). We used sciatic nerve transection models or spared nerve injury (SNI) models in the rat. In reverse transcriptase-polymerase chain reaction analysis, there were no significant differences between contralateral and ipsilateral DRGs of beta(1) and beta(2) mRNA 3 days after axotomy. beta(3) mRNA expression in ipsilateral DRGs increased significantly compared with contralateral DRGs 3 days after axotomy. In in situ hybridization histochemistry, beta(3) mRNA was predominantly expressed in medium- to large-size neurons, whereas beta(2) mRNA was expressed in small- to large-size neurons. There were no significant differences in beta(1) and beta(2) mRNA between contralateral and ipsilateral DRGs 3 days after axotomy. In contrast, beta(3) mRNA was mainly expressed in small neurons and occasionally in medium- to large-size neurons, and beta(3) mRNA expression in small c-type neurons in ipsilateral DRGs was increased significantly compared with contralateral DRGs. We examined beta(3) mRNA expression with one of alpha subunits, Na(v)1.3-ir, in DRG neurons after axotomy using the double labeling method. We found a high percentage of coexpression in injured DRG neurons: 83.6+/-2.8% of neurons expressing beta3 mRNA were labeled for Na(v)1.3-ir; 70.1+/-3.1% of Na(v)1.3-ir neurons expressed beta(3) mRNA. We also examined the expression of beta(3) mRNA in DRG neurons in the SNI model, a neuropathic pain model. We used activating transcription factor 3 to identify axotomized neurons, and found that beta(3) mRNA up-regulation occurred mainly in axotomized neurons in the neuropathic pain model. These data strongly suggest that beta(3) expression in injured DRG neurons following axotomy might be an important pathomechanism of post-nerve injury pain in primary sensory neurons. (C) 2003 IBRO. Published by Elsevier Ltd. All rights reserved.