Modulation of excetability in primary sensory neurons

最近的研究表明，新皮质锥体神经元的体细胞去极化反应在近侧轴突产生持续性钠电流(L_NAP)，但L_NAP是否参与了棘波的启动尚不清楚。在这里，我们展示了L_NAP在三叉神经中脑核初级感觉神经元的棘波起始中的潜在作用，该神经元表现出在三叉神经干轴突中启动的棘波向胞体反向传播，以响应胞体去极化。利鲁唑(10μM)和河豚毒素(10 NM)可使体细胞棘波(S棘波)的激活延迟或阈值逐步升高，但不影响刺激物本身。来自胞体和轴突丘(AH)的同步膜片钳记录显示，50 nM河豚毒素的浸浴增加了对胞体去极化反应的棘波激活的延迟，保持了从胞体到胞体的棘波回传时间不变。这表明激活延迟的增加发生在茎轴突。此外，在含QX-314和不含QX-314的贴片移液管引起的胞体到胞体浓度梯度减小的情况下，AH峰的幅度和最大上升速率(MRR)随重复脉冲注入的激活延迟的增加而降低，而S峰的幅度和最大上升速率的下降幅度和最大上升速率(MRR)明显小于QX-314。这表明，与S峰相比，AH峰更准确地反映了QX-314对轴突峰的衰减，与峰后向传播的性质一致。这些观察结果有力地表明，低电压激活的I_NAP参与了MTN神经元干轴突的棘波起始。

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.