NaN, a novel voltage-gated Na channel, is expressed preferentially in peripheral sensory neurons and down-regulated after axotomy
NaN, a novel voltage-gated Na channel, is expressed preferentially in peripheral sensory neurons and down-regulated after axotomy
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DOI：
10.1073/pnas.95.15.8963
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发表时间：
1998-07-21
影响因子：
11.1
通讯作者：
Waxman, SG
中科院分区：
文献类型：
--
作者：
Dib-Hajj, SD;Tyrrell, L;Waxman, SG
虽然生理学和药理学证据表明，在周围神经系统神经节的神经元中存在多个河豚毒素抗性(TTS-R)钠通道，但到目前为止，在这些细胞中只发现了一种SNS/PN3。我们已经鉴定和测序了一个新的钠通道铜亚单位(NaN)，它被预测为TTX-R和电压门控，在背根节(DRG)和三叉神经节内的感觉神经元中优先表达，预测的氨基酸序列可以与已知的Na通道α亚基的预测结构相比对；所有相关的标志性序列，包括带正电荷的S4和孔衬SS1-SS2片段，以及失活三肽IFM，都存在于预测位置。然而，NaN与包括SNS/PN3在内的其他哺乳动物的钠通道只有42-53%的相似性，这表明它是一个新的通道，并可能代表第三亚家族的钠通道。切断背根节神经元7天后，NAN转录水平显著降低，这与先前TTX-RNa电流减少的发现一致。轴索损伤后，NaN在DRG和三叉神经节中优先表达，在DRG中NaN的表达水平降低，提示NaN与SNS/PN3一起可能在外周感觉神经元产生TTX-R电流，并可能影响这些细胞的电活动的产生。
Although physiological and pharmacological evidence suggests the presence of multiple tetrodotoxin-resistant (TTS-R) Na channels in neurons of peripheral nervous system ganglia, only one, SNS/PN3, has been identified in these cells to date. we have identified and sequenced a novel Na channel cu-subunit (NaN), predicted to be TTX-R and voltage-gated, that is expressed preferentially in sensory neurons within dorsal root ganglia (DRG) and trigeminal ganglia, The predicted amino acid sequence of NaN can be aligned with the predicted structure of known Na channel alpha-subunits; all relevant landmark sequences, including positively charged S4 and pore-lining SS1-SS2 segments, and the inactivation tripeptide IFM, are present at predicted positions. However, NaN exhibits only 42-53% similarity to other mammalian Na channels, including SNS/PN3, indicating that it is a novel channel, and suggesting that it mag represent a third subfamily of Na channels. NaN transcript levels are reduced significantly 7 days post axotomy in DRG neurons, consistent with previous findings of a reduction in TTX-R Na currents. The preferential expression of NaN in DRG and trigeminal ganglia and the reduction of NaN mRNA levels in DRG after axonal injury suggest that NaN, together with SNS/PN3, may produce TTX-R currents in peripheral sensory neurons and may influence the generation of electrical activity in these cells.