Changes in Na+ channel currents of rat dorsal root ganglion neurons following axotomy and axotomy-induced autotomy
Changes in Na+ channel currents of rat dorsal root ganglion neurons following axotomy and axotomy-induced autotomy
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DOI：
10.1152/jn.00913.2001
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发表时间：
2002-11-01
影响因子：
2.5
通讯作者：
Smith, PA
中科院分区：
文献类型：
--
作者：
Abdulla, FA;Smith, PA
切断大鼠坐骨神经可使L-4-L-5背根神经节（DRG）神经元兴奋性增加。这些变化在那些表现出自残行为的动物中更为明显。我们使用全细胞记录来检查钠通道电流（I-Na）的河豚毒素敏感（TTX-S）和河豚毒素抵抗（TTX-R）组分的变化，这些组分可能有助于轴突切断诱导的兴奋性增加。细胞最初根据大小分为“大”、“中”和“小”组。TTX-S I-Na在“大”细胞中占优势，而TTX-R I-Na在一些但不是所有“小”细胞中占优势。因此，“小”细胞被细分为“小-慢”细胞和“小-快”细胞，“小-慢”细胞主要显示TTX-R I-Na，“小-快”细胞显示更多TTX-S I-Na。在其他实验室，其中使用略有不同的实验程序所获得的结果相反，我们发现，轴突切断增加TTX-R和/或TTX-S I-Na和减缓失活。这种影响在“小-慢”细胞中最大，在“大”细胞中最小。轴突切断促进的变化在表现出自切的动物中表达得更清楚。此外，存在的自切与转移的性质的I-Na在“大”，而不是“小慢”，假定的伤害性细胞。这些趋势平行于以前的观察轴突切开诱导的兴奋性，尖峰高度，尖峰宽度，也是最大的“小”细胞和最小的“大”细胞的增加。此外，自切的存在与“大”而不是“小”细胞的兴奋性增加相关。因此，TTX-R和TTX-S I-Na的增加与轴突切断诱导的整个感觉神经元群体的兴奋性增加和尖峰形状改变一致。这种类型的损伤引起的变化可能与人类慢性疼痛的发作有关。
Section of rat sciatic nerve (axotomy) increases the excitability of neurons in the L-4-L-5 dorsal root ganglia (DRG). These changes are more pronounced in animals that exhibit a self-mutilatory behavior known as autotomy. We used whole cell recording to examine changes in the tetrodotoxin-sensitive (TTX-S) and the tetrodotoxin-resistant (TTX-R) components of sodium channel currents (I-Na) that may contribute to axotomy-induced increases in excitability. Cells were initially divided on the basis of size into "large," "medium," and "small" groups. TTX-S I-Na predominated in "large" cells, whereas TTX-R I-Na predominated in some, but not all "small cells." "Small" cells were therefore subdivided into "small-slow" cells, which predominately exhibited TTX-R I-Na and "small fast" cells that exhibited more TTX-S I-Na. In contrast to results obtained in other laboratories, where slightly different experimental procedures were used, we found that axotomy increased TTX-R and/or TTX-S I-Na and slowed inactivation. The effects were greatest in "small-slow" cells and least in "large" cells. The changes promoted by axotomy were expressed more clearly in animals that exhibited autotomy. Also, the presence of autotomy correlated with a shift in the properties of I-Na in "large" rather than "small-slow," putative nociceptive cells. These trends parallel previous observations on axotomy-induced increases in excitability, spike height, and spike width that are also greatest in "small" cells and least in "large" cells. In addition, the presence of autotomy correlates with an increase in excitability of "large" rather than "small" cells. Increases in TTX-R and TTX-S I-Na thus coincide with axotomy-induced increases in excitability and alterations in spike shape across the whole population of sensory neurons. Injury-induced changes of this type are likely associated with the onset of chronic pain in humans.