Extracellular calcium controls the dynamic range of neuronal metabotropic glutamate receptor responses.
The metabotropicglutamate receptors (mGluRs) are neurotransmitter receptors important for synaptic plasticity in the brain. Here we report that native mGluR-mediated neuronal responses to glutamate are profoundly modulated by extracellular calcium (Ca2+(o)). In mouse cerebellar Purkinje cells (PCs), Ca2+(o) drastically broadened the effective dose range for glutamate analogs in which native mGluR1-mediated cation current and intracellular Ca2+ mobilization were evoked. This effect has not been observed for recombinant mGluRs expressed in the heterologous cell systems. Ca2+(o) also drastically augmented these native mGluR-mediated responses to the glutamate analog. These Ca2+(o) effects were observed in both the wild-type mice and the mutant mice expressing mGluR1 specifically in their PCs, suggesting that the native mGluR1 in the PCs but not those in other cell types are the key mediators of the effects. These findings demonstrate that Ca2+(o) plays an important role in regulating native mGluR-mediated neuronal responses.
Tabata
Toshihide
T
Department of Cellular Neurophysiology, Graduate School of Medical Science, Kanazawa University, 13-1 Takara-machi 920-8640, Japan.
Aiba
Atsu
A
Kano
Masanobu
M
D000818:Animals; D002118:Calcium / Q000378:metabolism* / Q000494:pharmacology; D002121:Calcium Channel Blockers / Q000494:pharmacology; D020013:Calcium Signaling / Q000187:drug effects / Q000502:physiology*; D002478:Cells, Cultured; D002614:Chelating Agents / Q000494:pharmacology; D004148:Dioxolanes / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004533:Egtazic Acid / Q000031:analogs & derivatives* / Q000494:pharmacology; D018690:Excitatory Amino Acid Agonists / Q000494:pharmacology; D005110:Extracellular Space / Q000187:drug effects / Q000378:metabolism*; D005260:Female; D005333:Fetus; D005998:Glycine / Q000031:analogs & derivatives / Q000494:pharmacology; D007093:Imidazoles / Q000494:pharmacology; D008297:Male; D008564:Membrane Potentials / Q000187:drug effects / Q000502:physiology; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D011687:Purines / Q000494:pharmacology; D011689:Purkinje Cells / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D018094:Receptors, Metabotropic Glutamate / Q000235:genetics / Q000378:metabolism*; D012118:Resorcinols / Q000494:pharmacology; D013569:Synapses / Q000187:drug effects / Q000378:metabolism* / Q000648:ultrastructure; D009435:Synaptic Transmission / Q000187:drug effects / Q000502:physiology*; D015854:Up-Regulation / Q000187:drug effects / Q000502:physiology
D002121:Calcium Channel Blockers; D002614:Chelating Agents; D004148:Dioxolanes; D018690:Excitatory Amino Acid Agonists; D007093:Imidazoles; D011687:Purines; D018094:Receptors, Metabotropic Glutamate; D012118:Resorcinols; C104077:metabotropic glutamate receptor type 1; C104068:4-(2-amino-6-chloro-9H-purin-9-yl)-1,3-dioxolane-2-methanol; D004533:Egtazic Acid; C079215:3,5-dihydroxyphenylglycine; C063159:1-(2-(3-(4-methoxyphenyl)propoxy)-4-methoxyphenylethyl)-1H-imidazole; C025603:1,2-bis(2-aminophenoxy)ethane-N,N,N',N'-tetraacetic acid; D002118:Calcium; D005998:Glycine