title: Metabotropic and ionotropic glutamate receptors regulate calcium channel currents in salamander retinal ganglion cells.
abstract: 1. Glutamate suppressed high-voltage-activated barium currents (IBa, HVA) in tiger salamander retinal ganglion cells. Both ionotropic (iGluR) and metabotropic (mGluR) receptors contributed to this calcium channel inhibition. 2. Trans-ACPD (1-aminocyclopentane-trans-1S,3R-dicarboxylic acid), a broad-spectrum metabotropic glutamate receptor agonist, suppressed a dihydropyridine-sensitive barium current. Kainate, an ionotropic glutamate receptor agonist, reduced an omega-conotoxin GVIA-sensitive current. 3. The relative effectiveness of selective agonists indicated that the predominant metabotropic receptor was the L-2-amino-4-phosphonobutyrate (L-AP4)-sensitive, group III receptor. This receptor reversed the action of forskolin, but this was not responsible for calcium channel suppression. l-AP4 raised internal calcium concentration. Antagonists of phospholipase C, inositol trisphosphate (IP3) receptors and ryanodine receptors inhibited the action of metabotropic agonists, indicating that group III receptor transduction was linked to this pathway. 4. The action of kainate was partially suppressed by BAPTA, by calmodulin antagonists and by blockers of calmodulin-dependent phosphatase. Suppression by kainate of the calcium channel current was more rapid when calcium was the charge carrier, instead of barium. The results indicate that calcium influx through kainate-sensitive glutamate receptors can activate calmodulin, which stimulates phosphatases that may directly suppress voltage-sensitive calcium channels. 5. Thus, ionotropic and metabotropic glutamate receptors inhibit distinct calcium channels. They could act synergistically, since both increase internal calcium. These pathways provide negative feedback that can reduce calcium influx when ganglion cells are depolarized.
authors.affiliation: Departments of Physiology and Biophysics, and Ophthalmology, School of Medicine, State University of New York, Buffalo, NY 14214, USA. WENSHEN@ACSU.BUFFALO.EDU
authors.forename: W
authors.initials: W
authors.lastname: Shen
authors.forename: M M
authors.initials: MM
authors.lastname: Slaughter
mesh_terms: D000557:Ambystoma / Q000378:metabolism*; D000613:Aminobutyrates / Q000494:pharmacology; D000818:Animals; D001464:Barium / Q000378:metabolism; D015220:Calcium Channels / Q000502:physiology*; D002614:Chelating Agents / Q000494:pharmacology; D003515:Cycloleucine / Q000031:analogs & derivatives / Q000494:pharmacology; D004533:Egtazic Acid / Q000031:analogs & derivatives / Q000494:pharmacology; D018690:Excitatory Amino Acid Agonists / Q000494:pharmacology; D066298:In Vitro Techniques; D007608:Kainic Acid / Q000494:pharmacology; D017470:Receptors, Glutamate / Q000502:physiology*; D018094:Receptors, Metabotropic Glutamate / Q000819:agonists / Q000502:physiology; D012165:Retinal Ganglion Cells / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects
chemical_list: D000613:Aminobutyrates; D015220:Calcium Channels; D002614:Chelating Agents; D018690:Excitatory Amino Acid Agonists; D017470:Receptors, Glutamate; D018094:Receptors, Metabotropic Glutamate; D003515:Cycloleucine; C036361:1-amino-1,3-dicarboxycyclopentane; D001464:Barium; D004533:Egtazic Acid; C012729:2-amino-4-phosphonobutyric acid; C025603:1,2-bis(2-aminophenoxy)ethane-N,N,N',N'-tetraacetic acid; D007608:Kainic Acid