Axotomy- and autotomy-induced changes in Ca2+ and K+ channel currents of rat dorsal root ganglion neurons
Axotomy- and autotomy-induced changes in Ca2+ and K+ channel currents of rat dorsal root ganglion neurons
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DOI：
10.1152/jn.2001.85.2.644
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发表时间：
2001-02-01
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
坐骨神经切断可增加大鼠背根神经节（DRG）神经元的兴奋性。用全细胞记录法检测了Ca 2+电流、K+电流、Ca 2+敏感性K+电流和超极化激活的阳离子电流（I-H）的变化。轴突切断对DRG各型神经元电导的影响相同。一般而言，在“小”细胞中观察到最大变化，在“大”细胞中观察到最小变化。高压激活的钙通道电流（HVA-I-Ba）减少轴突切断。虽然在轴突切断的神经元中记录的电流表现出增加的失活，但这并不能解释HVA-I-Ba的所有减少。激活动力学没有改变，并且用硝苯地平和/或ω-芋螺毒素GVIA的实验显示，在轴突切断后，L-型、N-型或“其他”HVA-I-Ba对总电流的贡献百分比没有改变。T型（低电压激活）的I-Ba不受轴突切断的影响。Ca ~（2+）敏感的K ~+电导（g（K，Ca））似乎降低，但当调整电压方案以引起相似量的Ca ~（2+）流入对照和轴突切断的细胞时，I-K，I-Ca（s）不变。轴突切断后，Cd 2+不敏感的稳态K+通道电流，主要包括延迟整流K+电流（I-K），在小型，中型和大型细胞减少约60%。这些数据表明，轴突切断诱导的兴奋性增加与减少I-K和/或减少g（K，Ca）是次要的钙离子内流减少。由于I-H被轴突切断术减少，因此该电流的变化不会导致兴奋性增加。I-Ba在所有细胞类型中的振幅和失活在表现出自残行为（自切）的动物中发生了更深刻的变化。这种行为的发生与大神经元的I-Ba显著减少相对应。这一发现支持了这样的假设，即可能与人类神经病理性疼痛相关的自切与大的有髓鞘感觉神经元的性质变化有关。
Sciatic nerve section (axotomy) increases the excitability of rat dorsal root ganglion (DRG) neurons. The changes in Ca2+ currents, K+ currents, Ca2+ sensitive K+ current, and hyperpolarization-activated cation current (I-H) that may be associated with this effect were examined by whole cell recording. Axotomy affected the same conductances in all types of DRG neuron. In general, the largest changes were seen in "small" cells and the smallest changes were seen in "large" cells. High-voltage-activated Ca2+-channel current (HVA-I-Ba) was reduced by axotomy. Although currents recorded in axotomized neurons exhibited increased inactivation, this did not account for all of the reduction in HVA-I-Ba. Activation kinetics were unchanged, and experiments with nifedipine and/or omega -conotoxin GVIA showed that there was no change in the percentage contribution of L-type, N-type, or "other" HVA-I-Ba to the total current after axotomy. T-type (low-voltage-activated) I-Ba was not affected by axotomy. Ca2+-sensitive K+ conductance (g(K,Ca)) appeared to be reduced, but when voltage protocols were adjusted to elicit similar amounts of Ca2+ influx into control and axotomized cells, I-K,I-Ca(s) were unchanged. After axotomy, Cd2+-insensitive, steady-state K+ channel current, which primarily comprised delayed rectifier K+ current (I-K), was reduced by about 60% in small, medium, and large cells. These data suggest that axotomy-induced increases in excitability are associated with decreases in I-K and/or decreases in g(K,Ca) that are secondary to decreased Ca2+-influx. Because I-H was reduced by axotomy, changes in this current do not contribute to increased excitability. The amplitude and inactivation of I-Ba in all cell types was changed more profoundly in animals that exhibited self-mutilatory behavior (autotomy). The onset of this behavior corresponded with significant reduction in I-Ba of large neurons. This finding supports the hypothesis that autotomy, that may be related to human neuropathic pain, is associated with changes in the properties of large myelinated sensory neurons.