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

J. Perroy, L. Prezèau, M. De Waard, R. Shigemoto, J. Bockaërt, L. Fagni, Journal of Neuroscience 20 (2000) 7896–7904.

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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.
Publishing Year
Date Published
2000-11-01
Journal Title
Journal of Neuroscience
Volume
20
Issue
21
Page
7896 - 7904
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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.
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.
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 20, no. 21 (2000): 7896–7904.
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, pp. 7896–7904, 2000.
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.
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.

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