Institute of Stomatology, Affiliated Hospital of Stomatology, Nanjing Medical University, 136 Hanzhong Road, Nanjing 210029, China.
Endocrine. 2012 Apr;41(2):274-80. doi: 10.1007/s12020-011-9573-z. Epub 2011 Dec 15.
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 (ERα and ERβ), 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 (αERKO and βERKO) 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 αERKO and βERKO mice, whereas Nav1.6 mRNA decreased in αERKO, but not in βERKO 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 ERα, ERβ, and another ER, whereas E2-regulation of Nav1.8 appears to be in an ERβ-dependent manner.
雌二醇（E2）在疼痛调制中起着关键作用，E2 的生物学效应通过与雌激素受体（ER）结合来传递。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）神经元可以表达 ER（ERα和 ERβ）和 Nav 通道（TTX-S：Nav1.1、Nav1.6 和 Nav1.7；和 TTX-R：Nav1.8 和 Nav1.9）。虽然 E2 调节 Nav 通道电流，但涉及的分子机制知之甚少。在这项研究中，我们研究了 Nav 通道亚型的 mRNA 表达，这些亚型由野生型（WT）和雌激素受体敲除（αERKO 和 βERKO）小鼠的 DRG 中的 ER 差异介导。通过定量实时 PCR，我们发现 Nav1.1、Nav1.7、Nav1.8 和 Nav1.9 亚型的表达在αERKO 和βERKO 小鼠中升高，而 Nav1.6 mRNA 在αERKO 中减少，但在βERKO 小鼠中没有。E2 处理的 WT 卵巢切除动物的 Nav 亚型 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 ERα、ERβ 和另一种 ER，而 E2 对 Nav1.8 的调节似乎依赖于 ERβ。
