Selective blockade of P/Q-type calcium channels by the metabotropic glutamate receptor type 7 involves a phospholipase C pathway in neurons Journal Article


Author(s): Perroy, Julie; Prezèau, Laurent; De Waard, Michel; Shigemoto, Ryuichi; Bockaërt, Joël L; Fagni, Laurent
Article Title: Selective blockade of P/Q-type calcium channels by the metabotropic glutamate receptor type 7 involves a phospholipase C pathway in neurons
Affiliation
Abstract: 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.
Keywords: Transfection; mGluR7; Ca2+ channels; Cerebellar granule cells; G-protein; PLC
Journal Title: Journal of Neuroscience
Volume: 20
Issue 21
ISSN: 1529-2401
Publisher: Society for Neuroscience  
Date Published: 2000-11-01
Start Page: 7896
End Page: 7904
Open access: no