Department of Physiology, Biophysics and Neuroscience, Centre for Research and Advanced Studies (Cinvestav), Mexico City, Mexico.
School of Medicine FES Iztacala, National Autonomous University of Mexico (UNAM), Tlalnepantla, Mexico.
Neuroscience. 2019 Aug 1;412:207-215. doi: 10.1016/j.neuroscience.2019.06.011. Epub 2019 Jun 18.
High voltage-activated (HVA) Ca (Ca) channels are oligomeric complexes formed by an ion-conducting main subunit (Cavα) and at least two auxiliary subunits (Cavβ and Caαδ). It has been reported that the expression of Caαδ1 increases in the dorsal root ganglia (DRGs) of animals with mechanical allodynia, and that the transcription factor Sp1 regulates the expression of the auxiliary subunit. Hence, the main aim of this work was to investigate the role of Sp1 as a molecular determinant of the exacerbated expression of Caαδ-1 in the nerve ligation-induced model of mechanical allodynia. Our results show that ligation of L5/L6 spinal nerves (SNL) produced allodynia and increased the expression of Sp1 and Caαδ-1 in the DRGs. Interestingly, intrathecal administration of the Sp1 inhibitor mithramycin A (Mth) prevented allodynia and decreased the expression of Sp1 and Caαδ-1. Likewise, electrophysiological recordings showed that incubation with Mth decreased Ca current density in the DRG neurons, acting mostly on HVA channels. These results suggest that L5/L6 SNL produces mechanical allodynia and increases the expression of the transcription factor Sp1 and the subunit Caαδ-1 in the DRGs, while Mth decreases mechanical allodynia and Ca currents through HVA channels in sensory neurons by reducing the functional expression of the Caαδ-1 subunit.
高电压激活（HVA）钙（Ca）通道是由离子传导主亚基（Cavα）和至少两个辅助亚基（Cavβ和Caαδ）组成的寡聚复合物。据报道，机械性痛觉过敏动物的背根神经节（DRG）中 Caαδ1 的表达增加，转录因子 Sp1 调节辅助亚基的表达。因此，这项工作的主要目的是研究 Sp1 作为分子决定因素在神经结扎诱导的机械性痛觉过敏模型中 Caαδ-1 过度表达的作用。我们的结果表明，L5/L6 脊神经（SNL）结扎产生痛觉过敏，并增加 DRG 中 Sp1 和 Caαδ-1 的表达。有趣的是，鞘内给予 Sp1 抑制剂米托蒽醌 A（Mth）可预防痛觉过敏并降低 Sp1 和 Caαδ-1 的表达。同样，电生理记录显示，Mth 孵育可降低 DRG 神经元中的钙电流密度，主要作用于 HVA 通道。这些结果表明，L5/L6 SNL 产生机械性痛觉过敏，并增加 DRG 中转录因子 Sp1 和亚基 Caαδ-1 的表达，而 Mth 通过减少 Caαδ-1 亚基的功能表达，降低感觉神经元中的机械性痛觉过敏和 HVA 通道中的钙电流。
