Electrophysiological and Pharmacological Analyses of Na(v)1.9 Voltage-Gated Sodium Channel by Establishing a Heterologous Expression System.
Electrophysiological and Pharmacological Analyses of Na(v)1.9 Voltage-Gated Sodium Channel by Establishing a Heterologous Expression System.
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通过建立异源表达系统对Na(v)1.9电压门控钠通道进行电生理和药理学分析
DOI：
10.3389/fphar.2017.00852
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发表时间：
2017
影响因子：
5.6
通讯作者：
Liu Z
中科院分区：
文献类型：
--
作者：
Zhou X;Xiao Z;Xu Y;Zhang Y;Tang D;Wu X;Tang C;Chen M;Shi X;Chen P;Liang S;Liu Z
NAV1.9电压门控性钠通道在外周伤害性感受神经元中优先表达。最近的研究已经证明了它在痛觉中的作用，但由于在哺乳动物细胞中异源表达的局限性，我们对Nav1.9的理解总体上是滞后的。本研究通过将绿色荧光蛋白与hNav1.9的C端融合，在ND7/23细胞中实现了人Nav1.9(hNav1.9)的功能性表达，为hNav1.9的电生理和药理学研究提供了可靠的方法。利用hNav1.9表达系统，我们研究了四个尚未确定电生理功能的hNav1.9突变(K419N、A582T、A842P和F1689L)的电生理特性。这四个突变显著地引起了稳态快速失活的正移，从而增加了hNav1.9的活性，这与痛性周围神经病的表型一致。同时，研究了炎症介质对hNav1.9的影响。令人印象深刻的是，组胺首次被发现可以增强hNav1.9的活性，表明它在hNav1.9调节炎性疼痛中起着至关重要的作用。综上所述，我们的研究为hNav1.9的研究提供了一个有用的平台，并为hNav1.9与疼痛的联系机制提供了新的见解。
Nav1. 9 voltage-gated sodium channel is preferentially expressed in peripheral nociceptive neurons. Recent progresses have proved its role in pain sensation, but our understanding of Nav1.9, in general, has lagged behind because of limitations in heterologous expression in mammal cells. In this work, functional expression of human Nav1.9 (hNav1.9) was achieved by fusing GFP to the C-terminal of hNav1.9 in ND7/23 cells, which has been proved to be a reliable method to the electrophysiological and pharmacological studies of hNav1.9. By using the hNav1.9 expression system, we investigated the electrophysiological properties of four mutations of hNav1.9 (K419N, A582T, A842P, and F1689L), whose electrophysiological functions have not been determined yet. The four mutations significantly caused positive shift of the steady-state fast inactivation and therefore increased hNav1.9 activity, consistent with the phenotype of painful peripheral neuropathy. Meanwhile, the effects of inflammatory mediators on hNav1.9 were also investigated. Impressively, histamine was found for the first time to enhance hNav1.9 activity, indicating its vital role in hNav1.9 modulating inflammatory pain. Taken together, our research provided a useful platform for hNav1.9 studies and new insight into mechanism of hNav1.9 linking to pain.
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DOI：
10.1073/pnas.1005633107
发表时间：
2010-07-06
影响因子：
11.1
作者：
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通讯作者：
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