Modulation of excetability in primary sensory neurons

初级感觉神经元兴奋性的调节

基本信息

批准号：
18500310
负责人：
KANG Youngnam
金额：
$ 2.5万
依托单位：
Osaka University
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (C)
财政年份：
2006
资助国家：
日本
起止时间：
2006 至 2007
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-18500310/
关键词：
Persistent Na^+ current Initiation of action notential Mesenceohalic triaeminal nucleus Riluzole Tetrodotoxin OX-314 Axon initial seanent Spike backpropagation

项目摘要

It has recently been shown that the persistent Na^+ current (l_NaP) is generated in the proximal axon in response to somatic depolarization in neocortical pyramidal neurons, while the involvement of l_NaP in spike-initiation is still unclear. Here we show a potential role of l_NaP in spike-initiation of primary sensory neurons in the mesencephalic trigeminal nucleus (MTN) that display a backpropagation of the spike initiated in the stem axon toward the soma in response to soma depolarization. Riluzole (10 μM) and tetrodotoxin (10 nM) caused an activation delay or a stepwise increase in the threshold for evoking soma spikes (S-spikes) without affecting the spike itself. Simultaneous patch-clamp recordings from the soma and axon hillock (AH) revealed that bath application of 50 nM tetrodotoxin increased the delay in spike activation in response to soma depolarization, leaving the spike-backpropagation time from the AH to soma unchanged. This indicates that the increase in activation delay occurred in the stem axon. Furthermore, under a decreasing intracellular concentration gradient of QX-314 from the soma to AH created by QX-314-containing and QX-314-free patch pipettes, the amplitude and maximum rate of rise (MRR) of AH-spikes decreased with an increase in the activation delay following repetition of current pulse injections, while S-spikes displayed much less decreases in amplitude and MRR. This suggests that comparing to S-spikes, AH-spikes more accurately reflect the attenuation of axonal-spike by QX-314, consistent with the spike-backpropagation nature. These observations strongly suggest that low-voltage-activated I_NaP is involved in spike-initiation in the stem axon of MTN neurons.

最近的研究表明，近端轴突中会产生持续的 Na^+ 电流（l_NaP），以响应新皮质锥体神经元的体细胞去极化，而 l_NaP 在尖峰启动中的参与尚不清楚，这里我们展示了其潜在的作用。 l_NaP 在中脑三叉神经核 (MTN) 初级感觉神经元的尖峰启动中的作用，显示出在干轴突中启动的尖峰向反向传播体细胞对体细胞去极化的反应导致激活延迟或引起体细胞尖峰（S-尖峰）的阈值逐步增加，而不影响同时膜片钳记录。来自体细胞和轴突小丘 (AH) 的研究表明，50 nM 河鲀毒素的浴应用增加了响应体细胞的尖峰激活的延迟去极化，使从 AH 到体细胞的尖峰反向传播时间不变，这表明在 QX-314 从体细胞到 AH 的细胞内浓度梯度下降的情况下，干轴突中发生了激活延迟。含 314 和不含 QX-314 的贴片移液器，AH 尖峰的幅度和最大上升率 (MRR) 随着重复电流脉冲后激活延迟的增加而降低注射，而 S 尖峰在幅度和 MRR 上显示出更少的降低，这表明与 S 尖峰相比，AH 尖峰更准确地反映了 QX-314 的轴突尖峰衰减，与尖峰反向传播性质一致。观察结果强烈表明，低电压激活的 I_NaP 参与了 MTN 神经元干轴突的尖峰启动。