--- _id: '2602' abstract: - lang: eng text: Although presynaptic localization of mGluR7 is well established, the mechanism by which the receptor may control Ca2+ channels in neurons is still unknown. We show here that cultured cerebellar granule cells express native metabotropic glutamate receptor type 7 (mGluR7) in neuritic processes, whereas transfected mGluR7 was also expressed in cell bodies. This allowed us to study the effect of the transfected receptor on somatic Ca2+ channels. In transfected neurons, mGuR7 selectively inhibited P/Q-type Ca2+ channels. The effect was mimicked by GTPγS and blocked by pertussis toxin (PTX) or a selective antibody raised against the G-protein αo subunit, indicating the involvement of a G(o)-like protein. The mGuR7 effect did not display the characteristics of a direct interaction between G-protein βγ subunits and the α1A Ca2+ channel subunit, but was abolished by quenching βγ subunits with specific intracellular peptides. Intracellular dialysis of G-protein βγ subunits did not mimic the action of mGluR7, suggesting that both G-protein βγ and αo subunits were required to mediate the effect. Inhibition of phospholipase C (PLC) blocked the inhibitory action of mGluR7, suggesting that a coincident activation of PLC by the G-protein βγ with αo subunits was required. The Ca2+ chelator BAPTA, as well as inhibition of either the inositol trisphosphate (IP3) receptor or protein kinase C (PKC) abolished the mGluR7 effect. Moreover, activation of native mGluR7 induced a PTX-dependent IP3 formation. These results indicated that IP3-mediated intracellular Ca2+ release was required for PKC-dependent inhibition of the Ca2+ channels. Possible control of synaptic transmission by the present mechanisms is discussed. acknowledgement: This work was supported by Centre National de la Recherche Scientifique and grants from Association Française contre les Myopathies, Fondation pour la Recherche Médicale, Bayer (France), and Hoechst-Marrion-Roussel (FRHMR1/9702). We thank J. P. Pin and F. Ango for constructive discussion of this work. We also thank Dr. J. Saugstad (Atlanta, GA) for the rat mGluR7a cDNA, J. M. Sabatier (Marseille, France) for the synthesis of the 68 AA peptide, V. Homburger (Montpellier, France) for the anti-Gαo antibody, and B. Mouillac (Montpellier, France) for the anti-cMyc monoclonal antibody. article_processing_charge: No article_type: original author: - first_name: Julie full_name: Perroy, Julie last_name: Perroy - first_name: Laurent full_name: Prezèau, Laurent last_name: Prezèau - first_name: Michel full_name: De Waard, Michel last_name: De Waard - first_name: Ryuichi full_name: Shigemoto, Ryuichi id: 499F3ABC-F248-11E8-B48F-1D18A9856A87 last_name: Shigemoto orcid: 0000-0001-8761-9444 - first_name: Joël full_name: Bockaërt, Joël last_name: Bockaërt - first_name: Laurent full_name: Fagni, Laurent last_name: Fagni citation: ama: Perroy J, Prezèau L, De Waard M, Shigemoto R, Bockaërt J, Fagni L. Selective blockade of P/Q-type calcium channels by the metabotropic glutamate receptor type 7 involves a phospholipase C pathway in neurons. Journal of Neuroscience. 2000;20(21):7896-7904. doi:10.1523/JNEUROSCI.20-21-07896.2000 apa: Perroy, J., Prezèau, L., De Waard, M., Shigemoto, R., Bockaërt, J., & Fagni, L. (2000). Selective blockade of P/Q-type calcium channels by the metabotropic glutamate receptor type 7 involves a phospholipase C pathway in neurons. Journal of Neuroscience. Society for Neuroscience. https://doi.org/10.1523/JNEUROSCI.20-21-07896.2000 chicago: Perroy, Julie, Laurent Prezèau, Michel De Waard, Ryuichi Shigemoto, Joël Bockaërt, and Laurent Fagni. “Selective Blockade of P/Q-Type Calcium Channels by the Metabotropic Glutamate Receptor Type 7 Involves a Phospholipase C Pathway in Neurons.” Journal of Neuroscience. Society for Neuroscience, 2000. https://doi.org/10.1523/JNEUROSCI.20-21-07896.2000. ieee: J. Perroy, L. Prezèau, M. De Waard, R. Shigemoto, J. Bockaërt, and L. Fagni, “Selective blockade of P/Q-type calcium channels by the metabotropic glutamate receptor type 7 involves a phospholipase C pathway in neurons,” Journal of Neuroscience, vol. 20, no. 21. Society for Neuroscience, pp. 7896–7904, 2000. ista: Perroy J, Prezèau L, De Waard M, Shigemoto R, Bockaërt J, Fagni L. 2000. Selective blockade of P/Q-type calcium channels by the metabotropic glutamate receptor type 7 involves a phospholipase C pathway in neurons. Journal of Neuroscience. 20(21), 7896–7904. mla: Perroy, Julie, et al. “Selective Blockade of P/Q-Type Calcium Channels by the Metabotropic Glutamate Receptor Type 7 Involves a Phospholipase C Pathway in Neurons.” Journal of Neuroscience, vol. 20, no. 21, Society for Neuroscience, 2000, pp. 7896–904, doi:10.1523/JNEUROSCI.20-21-07896.2000. short: J. Perroy, L. Prezèau, M. De Waard, R. Shigemoto, J. Bockaërt, L. Fagni, Journal of Neuroscience 20 (2000) 7896–7904. date_created: 2018-12-11T11:58:37Z date_published: 2000-11-01T00:00:00Z date_updated: 2023-05-03T09:48:17Z day: '01' doi: 10.1523/JNEUROSCI.20-21-07896.2000 extern: '1' external_id: pmid: - '11050109' intvolume: ' 20' issue: '21' language: - iso: eng main_file_link: - open_access: '1' url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6772734/ month: '11' oa: 1 oa_version: Published Version page: 7896 - 7904 pmid: 1 publication: Journal of Neuroscience publication_identifier: issn: - 0270-6474 publication_status: published publisher: Society for Neuroscience publist_id: '4296' quality_controlled: '1' scopus_import: '1' status: public title: Selective blockade of P/Q-type calcium channels by the metabotropic glutamate receptor type 7 involves a phospholipase C pathway in neurons type: journal_article user_id: ea97e931-d5af-11eb-85d4-e6957dddbf17 volume: 20 year: '2000' ...