17β-Estradiol regulates the gene expression of voltage-gated sodium channels: role of estrogen receptor α and estrogen receptor β
17β-Estradiol regulates the gene expression of voltage-gated sodium channels: role of estrogen receptor α and estrogen receptor β
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DOI：
10.1007/s12020-011-9573-z
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发表时间：
2012-04-01
期刊：
影响因子：
3.7
通讯作者：
Wang, Lin
中科院分区：
文献类型：
--
作者：
Hu, Fang;Wang, Qiang;Wang, Lin
雌激素（E2）在疼痛调节中起关键作用，E2的生物学效应是通过结合雌激素受体（ER）来传导的。电压门控钠（Nav）通道负责大多数神经元和可兴奋细胞的膜中动作电位的产生和传播。成年背根神经节（DRG）神经元可表达ER（ER α和ER β）和Nav通道（TTX-S：Nav1.1、Nav1.6和Nav1.7; TTX-R：Nav1.8和Nav1.9）。虽然E2调节Nav通道电流，但对所涉及的分子机制知之甚少。在这项研究中，我们研究了野生型（WT）和雌激素受体敲除（α ERKO和β ERKO）小鼠DRG中ER差异介导的Nav通道亚型的mRNA表达。通过实时定量PCR，我们发现Nav1.1，Nav1.7，Nav1.8和Nav1.9亚型的表达在α ERKO和β ERKO小鼠中升高，而Nav1.6 mRNA在α ERKO小鼠中降低，但在β ERKO小鼠中没有。在E2处理的WT卵巢切除动物中，Nav亚型的mRNA表达增加。我们还发现，E2对Nav1.1和Nav1.9 mRNA表达的调节依赖于ER α、ER β和另一种ER，而E2对Nav1.8的调节似乎是以ER β依赖的方式。
Estradiol (E2) plays a key role in pain modulation, and the biological effects of E2 are transduced by binding estrogen receptors (ERs). Voltage-gated sodium (Nav) channels are responsible for the generation and propagation of action potentials in the membranes of most neurons and excitable cells. Adult dorsal root ganglion (DRG) neurons can express the ERs (ER alpha and ER beta), and Nav channels (TTX-S: Nav1.1, Nav1.6, and Nav1.7; and TTX-R: Nav1.8, and Nav1.9). Although E2 modulates Nav channel currents, little is known about the molecular mechanisms involved. In this study, we investigate the mRNA expressions of Nav channel subtypes mediated differentially by the ERs in the DRGs of wild-type (WT) and estrogen receptor knockout (alpha ERKO and beta ERKO) mice. By means of quantitative real-time PCR, we found that the expressions of Nav1.1, Nav1.7, Nav1.8, and Nav1.9 subtypes were elevated in alpha ERKO and beta ERKO mice, whereas Nav1.6 mRNA decreased in alpha ERKO, but not in beta ERKO mice. The mRNA expressions of Nav subtypes were increased in E2-treated WT ovariectomized animals. We also found that E2-regulation of Nav1.1 and Nav1.9 mRNA expressions is dependent on ER alpha, ER beta, and another ER, whereas E2-regulation of Nav1.8 appears to be in an ER beta-dependent manner.