title: Functional coupling of the metabotropic glutamate receptor, InsP3 receptor and L-type Ca2+ channel in mouse CA1 pyramidal cells.
abstract: Activity-dependent regulation of calcium dynamics in neuronal cells can play significant roles in the modulation of many cellular processes such as intracellular signalling, neuronal activity and synaptic plasticity. Among many calcium influx pathways into neurons, the voltage-dependent calcium channel (VDCC) is the major source of calcium influx, but its modulation by synaptic activity has still been under debate. While the metabotropic glutamate receptor (mGluR) is supposed to modulate L-type VDCCs (L-VDCCs), its reported actions include both facilitation and suppression, probably reflecting the uncertainty of both the molecular targets of the mGluR agonists and the source of the recorded calcium signal in previous reports. In this study, using subtype-specific knockout mice, we have shown that mGluR5 induces facilitation of the depolarization-evoked calcium current. This facilitation was not accompanied by the change in single-channel properties of the VDCC itself; instead, it required the activation of calcium-induced calcium release (CICR) that was triggered by VDCC opening, suggesting that the opening of CICR-coupled cation channels was essential for the facilitation. This facilitation was blocked or reduced by the inhibitors of both L-VDCCs and InsP3 receptors (InsP3Rs). Furthermore, L-VDCCs and mGluR5 were shown to form a complex by coimmunoprecipitation, suggesting that the specific functional coupling between mGluR5, InsP3Rs and L-VDCCs played a pivotal role in the calcium-current facilitation. Finally, we showed that mGluR5 enhanced VDCC-dependent long-term potentiation (LTP) of synaptic transmission. Our study has identified a novel mechanism of the interaction between the mGluR and calcium signalling, and suggested a contribution of mGluR5 to synaptic plasticity.
authors.affiliation: Division of Neuronal Network, Department of Basic Medical Sciences, Institute of Medical Science, University of Tokyo, Tokyo, 108-8639, Japan.
authors.forename: Hiroyuki K
authors.initials: HK
authors.lastname: Kato
authors.forename: Hidetoshi
authors.initials: H
authors.lastname: Kassai
authors.forename: Ayako M
authors.initials: AM
authors.lastname: Watabe
authors.forename: Atsu
authors.initials: A
authors.lastname: Aiba
authors.forename: Toshiya
authors.initials: T
authors.lastname: Manabe
mesh_terms: D000818:Animals; D056547:CA1 Region, Hippocampal / Q000502:physiology*; D020746:Calcium Channels, L-Type / Q000502:physiology*; D066298:In Vitro Techniques; D053496:Inositol 1,4,5-Trisphosphate Receptors / Q000502:physiology*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D017966:Pyramidal Cells / Q000502:physiology*; D064529:Receptor, Metabotropic Glutamate 5; D018094:Receptors, Metabotropic Glutamate / Q000502:physiology*
chemical_list: D020746:Calcium Channels, L-Type; C578936:Grm5 protein, mouse; D053496:Inositol 1,4,5-Trisphosphate Receptors; D064529:Receptor, Metabotropic Glutamate 5; D018094:Receptors, Metabotropic Glutamate