Department of Physiology, School of Life Dentistry at Tokyo, Nippon Dental University, 1-9-20, Fujimi-cho, Chiyoda-ku, Tokyo 102-8159, Japan Research Center for Odontology, School of Life Dentistry at Tokyo, Nippon Dental University, 1-9-20, Fujimi-cho, Chiyoda-ku, Tokyo 102-8159, Japan.
Pain. 2011 Sep;152(9):2147-2156. doi: 10.1016/j.pain.2011.05.023. Epub 2011 Jun 15.
Previous studies indicate that silencing Kir4.1, a specific inward rectifying K(+) (Kir) channel subunit, in sensory ganglionic satellite glial cells (SGCs) induces behavioral hyperalgesia. However, the function of Kir4.1 channels in SGCs in vivo under pathophysiological conditions remains to be determined. The aim of the present study was to examine whether peripheral inflammation in anesthetized rats alters the SGC Kir4.1 current using in vivo patch clamp and immunohistochemical techniques. Inflammation was induced by injection of complete Freund's adjuvant into the whisker pad. The threshold of escape from mechanical stimulation applied to the orofacial area in inflamed rats was significantly lower than in naïve rats. The mean percentage of small/medium diameter trigeminal ganglion (TRG) neurons encircled by Kir4.1-immunoreactive SGCs in inflamed rats was also significantly lower than in naïve rats. In vivo whole-cell recordings were made using SGCs in the trigeminal ganglia (TRGs). Increasing extracellular K(+) concentrations resulted in significantly smaller potentiation of the mean peak amplitude of the Kir current in inflamed compared with naïve rats. In addition, the density of the Ba(2+)-sensitive Kir current associated with small-diameter TRG neurons was significantly lower in inflamed rats compared with naïve rats. Mean membrane potential in inflamed rats was more depolarized than in naïve rats. These results suggest that inflammation could suppress Kir4.1 currents of SGCs in the TRGs and that this impairment of glial potassium homeostasis in the TRGs contributes to trigeminal pain. Therefore, the Kir4.1 channel in SGCs may be a new molecular target for the treatment of trigeminal inflammatory pain.
先前的研究表明，沉默感觉神经节卫星胶质细胞（SGC）中的 Kir4.1，一种特定的内向整流钾（Kir）通道亚基，会导致行为性痛觉过敏。然而，在病理生理条件下，SGC 中的 Kir4.1 通道的功能仍有待确定。本研究旨在使用体内膜片钳和免疫组织化学技术，检测麻醉大鼠外周炎症是否会改变 SGC 的 Kir4.1 电流。通过向胡须垫注射完全弗氏佐剂诱导炎症。与未处理大鼠相比，炎性大鼠逃避口腔区域机械刺激的阈值明显更低。在炎性大鼠中，被 Kir4.1 免疫反应性 SGC 环绕的小/中直径三叉神经节（TRG）神经元的平均百分比也明显低于未处理大鼠。使用 TRG 中的 SGC 进行体内全细胞膜片钳记录。增加细胞外 K+浓度导致炎症大鼠 Kir 电流的平均峰值幅度的增强明显小于未处理大鼠。此外，与小直径 TRG 神经元相关的 Ba2+敏感 Kir 电流密度在炎性大鼠中明显低于未处理大鼠。炎性大鼠的平均膜电位比未处理大鼠更去极化。这些结果表明，炎症可能会抑制 TRG 中 SGC 的 Kir4.1 电流，而这种 TRG 中胶质钾离子稳态的损害可能导致三叉神经痛。因此，SGC 中的 Kir4.1 通道可能是治疗三叉神经炎性疼痛的新分子靶点。
