Song Ji-Hyeon, Park Eun-Sung, Han Sang-Mi, Han Seung-Ro, Ahn Dong-Kuk, Youn Dong-Ho
Department of Oral Physiology, School of Dentistry and Brain Korea 21, Brain Science and Engineering Institute, Kyungpook National University, 188-1 Samduk-2-ga, Chung-gu, Daegu 700-412, Korea.
Mol Pain. 2009 Sep 2;5:50. doi: 10.1186/1744-8069-5-50.
Group I mGluRs (mGluR1 and 5) pre- and/or postsynaptically regulate synaptic transmission at glutamatergic synapses. By recording spontaneous EPSCs (sEPSCs) in the spinal trigeminal subnucleus oralis (Vo), we here investigated the regulation of glutamatergic transmission through the activation of group I mGluRs. Bath-applied DHPG (10 microM/5 min), activating the group I mGluRs, increased sEPSCs both in frequency and amplitude; particularly, the increased amplitude was long-lasting. The DHPG-induced increases of sEPSC frequency and amplitude were not NMDA receptor-dependent. The DHPG-induced increase in the frequency of sEPSCs, the presynaptic effect being further confirmed by the DHPG effect on paired-pulse ratio of trigeminal tract-evoked EPSCs, an index of presynaptic modulation, was significantly but partially reduced by blockades of voltage-dependent sodium channel, mGluR1 or mGluR5. Interestingly, PKC inhibition markedly enhanced the DHPG-induced increase of sEPSC frequency, which was mainly accomplished through mGluR1, indicating an inhibitory role of PKC. In contrast, the DHPG-induced increase of sEPSC amplitude was not affected by mGluR1 or mGluR5 antagonists although the long-lasting property of the increase was disappeared; however, the increase was completely inhibited by blocking both mGluR1 and mGluR5. Further study of signal transduction mechanisms revealed that PLC and CaMKII mediated the increases of sEPSC in both frequency and amplitude by DHPG, while IP3 receptor, NO and ERK only that of amplitude during DHPG application. Altogether, these results indicate that the activation of group I mGluRs and their signal transduction pathways differentially regulate glutamate release and synaptic responses in Vo, thereby contributing to the processing of somatosensory signals from orofacial region.
I 型代谢型谷氨酸受体（mGluR1 和 5）在突触前和/或突触后调节谷氨酸能突触的突触传递。通过记录三叉神经脊髓束核口部（Vo）的自发性兴奋性突触后电流（sEPSCs），我们在此研究了通过激活 I 型代谢型谷氨酸受体对谷氨酸能传递的调节。浴加应用 DHPG（10 μM/5 分钟）激活 I 型代谢型谷氨酸受体，增加了 sEPSCs 的频率和幅度；特别是，增加的幅度是持久的。DHPG 诱导的 sEPSC 频率和幅度增加不依赖于 NMDA 受体。DHPG 诱导的 sEPSCs 频率增加，通过 DHPG 对三叉神经束诱发的 EPSCs 的配对脉冲比率的影响进一步证实了其突触前效应，这是突触前调制的一个指标，被电压依赖性钠通道、mGluR1 或 mGluR5 的阻断显著但部分降低。有趣的是，蛋白激酶 C（PKC）抑制显著增强了 DHPG 诱导的 sEPSC 频率增加，这主要是通过 mGluR1 实现的，表明 PKC 具有抑制作用。相比之下，DHPG 诱导的 sEPSC 幅度增加不受 mGluR1 或 mGluR5 拮抗剂的影响，尽管增加的持久特性消失了；然而，同时阻断 mGluR1 和 mGluR5 可完全抑制增加。对信号转导机制的进一步研究表明，磷脂酶 C（PLC）和钙/钙调蛋白依赖性蛋白激酶 II（CaMKII）介导了 DHPG 引起的 sEPSC 在频率和幅度上的增加，而肌醇三磷酸受体（IP3 受体）、一氧化氮（NO）和细胞外信号调节激酶（ERK）仅介导了 DHPG 应用期间幅度的增加。总之，这些结果表明 I 型代谢型谷氨酸受体的激活及其信号转导途径在 Vo 中差异调节谷氨酸释放和突触反应，从而有助于处理来自口面部区域的躯体感觉信号。
