Modulation of excetability in primary sensory neurons

最近的研究表明，在新皮层锥体神经元中，当体细胞去极化时，近端轴突中产生持续性Na^+电流（l_NaP），但l_NaP是否参与锋电位起始尚不清楚。在这里，我们显示了潜在的作用，l_NaP在初级感觉神经元在中脑三叉神经核（MTN），显示了反向传播的尖峰开始在干轴突向索马在响应索马去极化。阿曲唑（10 μM）和河豚毒素（10 nM）引起激活延迟或诱发索马尖峰（S-尖峰）的阈值逐步增加，而不影响尖峰本身。从索马和轴突丘（AH）的同时膜片钳记录显示，浴应用50 nM河豚毒素增加了响应于索马去极化的尖峰激活的延迟，留下从AH到索马的尖峰反向传播时间不变。这表明激活延迟的增加发生在干轴突中。此外，在含QX-314和不含QX-314的贴片移液器产生的从索马到AH的QX-314细胞内浓度梯度降低的情况下，AH峰电位的振幅和最大上升速率（MRR）随着重复电流脉冲注射后激活延迟的增加而降低，而S峰电位的振幅和MRR降低幅度要小得多。这表明与S-尖峰相比，AH-尖峰更准确地反映了QX-314对轴突尖峰的衰减，与尖峰反向传播性质一致。这些结果强烈地表明，低电压激活的I_NaP参与了MTN神经元干轴突的锋电位起始。

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.