Altered expression and function of sodium channels in large DRG neurons and myelinated A-fibers in early diabetic neuropathy in the rat
Altered expression and function of sodium channels in large DRG neurons and myelinated A-fibers in early diabetic neuropathy in the rat
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DOI：
10.1016/j.bbrc.2005.11.057
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发表时间：
2006-01-13
影响因子：
3.1
通讯作者：
Wiley, JW
中科院分区：
文献类型：
--
作者：
Hong, SS;Wiley, JW
小伤害性C纤维DRG神经元中钠通道的差异性改变与糖尿病神经病变有关。在这项研究中，我们研究了糖尿病大鼠背根神经节A纤维大神经元的钠电流和钠通道的表达。与对照组相比，糖尿病大鼠的大神经元在总钠电流和TTX-S钠电流方面均表现出显著增加，并且在其电压依赖性激活动力学方面表现出类似于-15 mV的偏移。TTX-R Na（v）1.9钠电流也显著增加，而TTX-R Na（v）1.8电流在糖尿病大鼠神经元中未观察到改变。快电压斜坡或慢电压斜坡诱导的钠电流在糖尿病神经元中也显著增加。免疫荧光研究表明，糖尿病大鼠表达Na（v）1.2，Na（v）1.3，Na（v）1.7和Na（v）1.9的大DRG神经元的水平和数量显着增加，而Na（v）1.8减少。我们还观察到表达Na（v）1.8的Ranvier淋巴结数量减少，淋巴结中Na（v）1.6和Na（v）1.8的染色强度降低。我们的研究结果表明，钠通道的改变发生在大DRG神经元和A-纤维，并可能在糖尿病感觉神经病变中发挥重要作用。(c)2005年爱思唯尔公司All rights reserved.
Differential alterations of sodium channels in small nociceptive C-fiber DRG neurons have been implicated in diabetic neuropathy. In this study, we investigated sodium currents and the expression of sodium channels in large A-fiber DRG neurons in diabetic rats. Compared with controls, large neurons from diabetic rats showed significant increases in both total and TTX-S sodium currents and similar to- 15 mV shifts in their voltage-dependent activation kinetics. TTX-R Na(v)1.9 sodium current was also significantly increased, whereas no alteration of TTX-R Na(v)1.8 current was observed in neurons from diabetic rats. Sodium current induced by fast- or slow-voltage ramps increased markedly in the diabetic neurons as well. Immunofluorescence studies showed significant increases in the levels and number of large DRG neurons from diabetic rats expressing Na(v)1.2, Na(v)1.3, Na(v)1.7, and Na(v)1.9 whereas Na(v)1.8 decreased. We also observed a decrease in the number of nodes of Ranvier expressing Na(v)1.8 and in staining intensity of Na(v)1.6 and Na(v)1.8 at nodes. Our results suggest that alterations of sodium channels occur in large DRG neurons and A-fibers, and may play an important role in diabetic sensory neuropathy. (c) 2005 Elsevier Inc. All rights reserved.