Sensory neuron-derived Na v 1.7 contributes to dorsal horn neuron excitability
Sensory neuron-derived Na v 1.7 contributes to dorsal horn neuron excitability
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感觉神经元衍生的 Na v 1.7 有助于背角神经元兴奋性
DOI：
10.1101/551747
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发表时间：
2019
期刊：
影响因子：
--
通讯作者：
Alles S
中科院分区：
文献类型：
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作者：
Alles S
感觉神经元中电压门控钠通道 NaV1.7 的表达是疼痛感觉所必需的。我们使用表位标记的 NaV1.7 敲入小鼠检查了 NaV1.7 在脊髓背角中的作用。免疫电子显微镜显示，尽管不存在 mRNA，但浅表背角神经元的树突中存在 NaV1.7。 L5 传入神经根切断术降低了背角 NaV1.7 的水平。周围神经系统特异性 NaV1.7 缺失突变小鼠表现出中枢缺陷，第二层背角强直放电神经元数量减少一半以上，单个尖峰神经元数量增加一倍以上。 NaV1.7 阻断剂 PF05089771 降低了背角神经元的兴奋性，但对 NaV1.7 缺失突变小鼠没有影响。这些数据证明了初级传入神经元产生的 NaV1.7 在背角神经元中的意想不到的功能作用以及转录组分析无法预测的表达模式。
Expression of the voltage-gated sodium channel NaV1.7 in sensory neurons is required for pain sensation. We examined the role of NaV1.7 in the dorsal horn of the spinal cord using an epitope-tagged NaV1.7 knock-in mouse. Immuno–electron microscopy showed the presence of NaV1.7 in dendrites of superficial dorsal horn neurons, despite the absence of mRNA. Rhizotomy of L5 afferent nerves lowered the levels of NaV1.7 in the dorsal horn. Peripheral nervous system–specific NaV1.7 null mutant mice showed central deficits, with lamina II dorsal horn tonic firing neurons more than halved and single spiking neurons more than doubled. NaV1.7 blocker PF05089771 diminished excitability in dorsal horn neurons but had no effect on NaV1.7 null mutant mice. These data demonstrate an unsuspected functional role of primary afferent neuron-generated NaV1.7 in dorsal horn neurons and an expression pattern that would not be predicted by transcriptomic analysis.