Liu H, Duan S-R
Department of Neurology, The Fourth Affiliated Hospital of Harbin Medical University, Harbin, China.
Department of Neurology, The First Affiliated Hospital of Harbin Medical University, Harbin, China.
Neuroscience. 2016 Apr 21;320:194-204. doi: 10.1016/j.neuroscience.2016.02.008. Epub 2016 Feb 8.
Prostaglandin-E2 (PGE2) is a very important inflammatory mediator and PGE2-mediated neuroexcitation in sex-specific distribution of Ah-type trigeminal ganglion neurons (TGNs) isolated from adult female rats is not fully addressed. The whole-cell patch-clamp experiment was performed to verify the effects of PGE2, forskolin, and GPR30-selective agonist (G-1) on action potential (AP) and tetrodotoxin-resistant (TTX-R) Na(+) currents in identified Ah-type TGNs. The results showed that the firing frequency was increased in Ah- and C-types by PGE2, which was simulated by forskolin and inhibited by Rp-cyclic adenosine monophosphate (cAMP), while G-1 mimicked this effect only in Ah-types, which was abolished by GPR30-selective antagonist (G-15). Although the amplitude of AP was increased in Ah- and C-types, increased maximal upstroke velocity was confirmed only in Ah-types, suggesting distinct alternations in current density and/or voltage-dependent property of Na(+) channels. With 1.0 μM PGE2, TTX-R Na(+) currents were upregulated without changing the current-voltage relationship and voltage-dependent activation in C-types, however, the TTX-R Na(+) current was augmented in Ah-types, peaked voltage and the voltage-dependent activation were both shifted toward hyperpolarized direction with faster slope. Intriguingly, the low-threshold persistent TTX-R component was activated from -60 mV and increased almost double at -30 mV compared with ∼30-40% increment of TTX-R component being activated at ∼-10 mV. Additionally, the change in TTX-R component of Ah-types was equivalent well with that in C-type TGNs. Taken these data together, we conclude that PGE2 modulates the neuroexcitation via cAMP-mediated upregulation of TTX-R Na(+) currents in both cell-types with hormone-dependent feature, especially persistent TTX-R Na(+) currents in sex-specific distribution of myelinated Ah-type TGNs.
前列腺素 - E2（PGE2）是一种非常重要的炎症介质，而成年雌性大鼠分离出的Ah型三叉神经节神经元（TGNs）中PGE2介导的神经兴奋在性别特异性分布方面尚未得到充分研究。进行全细胞膜片钳实验以验证PGE2、福斯高林和GPR30选择性激动剂（G - 1）对已鉴定的Ah型TGNs动作电位（AP）和河豚毒素抗性（TTX - R）钠电流的影响。结果表明，PGE2使Ah型和C型神经元的放电频率增加，福斯高林可模拟此效应，而Rp - 环磷酸腺苷（cAMP）可抑制该效应，G - 1仅在Ah型神经元中模拟此效应，且被GPR30选择性拮抗剂（G - 15）消除。虽然Ah型和C型神经元的AP幅度均增加，但仅在Ah型神经元中确认最大上升速度增加，这表明钠通道的电流密度和/或电压依赖性特性存在明显差异。使用1.0 μM PGE2时，C型神经元中TTX - R钠电流上调，而电流 - 电压关系和电压依赖性激活未改变，然而，Ah型神经元中TTX - R钠电流增加，峰值电压和电压依赖性激活均向超极化方向移动且斜率更快。有趣的是，低阈值持续性TTX - R成分在 - 60 mV时被激活，在 - 30 mV时增加近一倍，而在约 - 10 mV时被激活的TTX - R成分增加约30 - 40%。此外，Ah型神经元中TTX - R成分的变化与C型TGNs中的变化相当。综合这些数据，我们得出结论，PGE2通过cAMP介导的TTX - R钠电流上调在两种细胞类型中调节神经兴奋，具有激素依赖性特征，尤其是在有髓Ah型TGNs的性别特异性分布中持续性TTX - R钠电流。
