---
_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'
...