The sodium channel auxiliary subunits β1 and β2 are differentially expressed in the spinal cord of neuropathic rats
The sodium channel auxiliary subunits β1 and β2 are differentially expressed in the spinal cord of neuropathic rats
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DOI：
10.1016/s0306-4522(98)00415-1
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发表时间：
1999-01-01
期刊：
影响因子：
3.3
通讯作者：
Fleetwood-Walker, SM
中科院分区：
文献类型：
--
作者：
Blackburn-Munro, G;Fleetwood-Walker, SM
神经病理性疼痛被认为是由周围神经系统损伤部位的异位放电引起的，表现为初级传入纤维及其在脊髓内的突触接触的神经元兴奋性水平的普遍增加。电压激活的钠通道阻滞剂，如拉莫三嗪，已被证明在治疗神经病理性疼痛方面临床上有效。Na+通道在结构上是多样的，包括一个主要的α亚基(其中有不同的异构体)和两个辅助的亚基，称为β1和β2。这两个β亚基都影响通道的激活和失活速率，并可以改变质膜内的α亚基密度。此外，这些亚基可能与细胞外基质分子相互作用，影响轴突的生长和髓鞘形成。应用原位杂交组织化学方法，我们发现神经病大鼠脊髓背角中β1和β2亚单位的表达受坐骨神经慢性压迫性损伤的不同调节。在神经病变后12-15天，与对侧相比，同侧脊髓板层I、II内的β1信使RNA水平显著升高，而β2信使RNA水平显著降低。在板层III-IV内，P2信使RNA水平在同侧较对侧略有下降，而β1信使RNA的表达保持不变。因此，不同的β亚基类型的不同调节(通过对Na+通道功能的不同影响)可能有助于神经病理性损伤后中枢神经元兴奋性的改变。(C)1999年IBRO。爱思唯尔科学有限公司出版。
Neuropathic pain is thought to arise from ectopic discharges at the site of injury within the peripheral nervous system, and is manifest as a general increase in the level of neuronal excitability within primary afferent fibres and their synaptic contacts within the spinal cord. Voltage-activated Na+ channel blockers such as lamotrigine have been shown to be clinically effective in the treatment of neuropathic pain. Na+ channels are structurally diverse comprising a principal alpha subunit (of which there are variable isoforms) and two auxiliary subunits termed beta 1 and beta 2. Both beta subunits affect the rates of channel activation and inactivation, and can modify alpha subunit density within the plasma membrane. In addition, these subunits may interact with extracellular matrix molecules to affect growth and myelination of axons. Using in situ hybridization histochemistry we have shown that the expression of the beta 1 and beta 2 subunits within the dorsal horn of the spinal cord of neuropathic rats is differentially regulated by a chronic constrictive injury to the sciatic nerve. At days 12-15 post-neuropathy, beta 1 messenger RNA levels had increased, whereas beta 2 messenger RNA levels had decreased significantly within laminae I, II on the ipsilateral side of the cord relative to the contralateral side. Within laminae III-IV P2 messenger RNA levels showed a small but significant decrease on the ipsilateral side relative to the contralateral side, whilst expression of beta 1 messenger RNA remained unchanged.Thus, differential regulation of the individual beta subunit types may (through their distinct influences on Na+ channel function) contribute to altered excitability of central neurons after neuropathic injury. (C) 1999 IBRO. Published by Elsevier Science Ltd.