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.

最近已经显示，持续的Na^+电流（L_NAP）是在新皮层金字塔神经元中响应体细胞沉积的近端轴突中生成的，而L_NAP在Spike引入中的参与仍然不清楚。在这里，我们显示了L_NAP在Messencephalic三叉神经核（MTN）中原代感觉神经元的尖峰引入中的潜在作用，该核素（MTN）显示出在茎轴突中启动的尖峰的反向传播，该尖峰响应于Soma depolarisis，朝向SOMA。 riluzole（10μM）和四毒素（10 nm）导致激活延迟或逐步增加触发soma尖峰（S-Spikes）的阈值，而不会影响峰值本身。来自SOMA和Axon Hillock（AH）的同时贴片钳记录显示，沐浴在50 nm四毒素的应用增加了响应SOMA沉积时尖峰激活的延迟，从而使Spike-BackPropagation时间从AH到SOMA到SOMA的峰值延迟不变。这表明激活延迟的增加发生在茎轴突中。 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 amplifier 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 declines in amplifier and MRR.这表明，与S尖头相比，AH尖峰更准确地反映了QX-314对轴突尖峰的衰减，这与尖峰 - 背propagation性质一致。这些观察结果强烈表明，低压激活的I_NAP参与MTN神经元茎轴突的尖峰。