Signal Transduction Mechanisms Underlying Group I mGluR-mediated Increase in Frequency and Amplitude of Spontaneous EPSCs in the Spinal Trigeminal Subnucleus Oralis of the Rat

Song Ji-Hyeon, Park Eun-Sung, Han Sang-Mi, Han Seung-Ro, Ahn Dong-Kuk, Youn, Youn Dong-Ho

Description

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 μM/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 IP 3 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.

Informations

• Publié par: biomed
• Publié le: 01 janvier 2009
• Nombre de lectures: 5
• Langue: English

Extrait

Molecular Pain

BioMedCentral

Open Access Research Signal Transduction Mechanisms Underlying Group I mGluRmediated Increase in Frequency and Amplitude of Spontaneous EPSCs in the Spinal Trigeminal Subnucleus Oralis of the Rat † † JiHyeon Song, EunSung Park, SangMi Han, SeungRo Han, Dong Kuk Ahn and DongHo Youn*

Address: 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 Email: JiHyeon Song  [e-mail]; EunSung Park  [e-mail]; SangMi Han  [e-mail]; Seung Ro Han  [e-mail]; DongKuk Ahn  [e-mail]; DongHo Youn*  [e-mail] * Corresponding author†Equal contributors

Published: 2 September 2009Received: 25 March 2009 Accepted: 2 September 2009 Molecular Pain2009,5:50 doi:10.1186/17448069550 This article is available from: http://www.molecularpain.com/content/5/1/50 © 2009 Song et al; licensee BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Abstract 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 (10μM/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 IP receptor,NO and ERK only that of amplitude during DHPG application. Altogether, these 3 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.

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