Metabotropic and ionotropic glutamate receptors regulate calcium channel currents in salamander retinal ganglion cells

Metabotropic and ionotropic glutamate receptors regulate calcium channel currents in salamander... 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 ω‐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. http://www.deepdyve.com/assets/images/DeepDyve-Logo-lg.png The Journal of Physiology Wiley

Metabotropic and ionotropic glutamate receptors regulate calcium channel currents in salamander retinal ganglion cells

The Journal of Physiology, Volume 510 (3) – Aug 1, 1998

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Publisher
Wiley
Copyright
Copyright © 1998 Wiley Subscription Services, Inc., A Wiley Company
ISSN
0022-3751
eISSN
1469-7793
D.O.I.
10.1111/j.1469-7793.1998.815bj.x
Publisher site
See Article on Publisher Site

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 ω‐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.

Journal

The Journal of PhysiologyWiley

Published: Aug 1, 1998

References

  • Depression of a sustained calcium current by kainate in rat hippocampal neurones in vitro
    Nistri, Nistri; Cherubini, Cherubini
  • The metabotropic glutamate receptors: structure and function
    Pin, Pin; Duvoisin, Duvoisin
  • Excitatory amino acid agonist‐antagonist interactions at 2‐amino‐4‐phosphonobutyric acid‐sensitive quisqualate receptors coupled to phosphoinositide hydrolysis in slices of rat hippocampus
    Schoepp, Schoepp; Johnson, Johnson
  • Pharmacology of selective and non‐selective metabotropic glutamate receptor agonists at L‐AP4 receptors in retinal ON bipolar cells
    Thoreson, Thoreson; Ulphani, Ulphani
  • Pharmacological similarity between the retinal APB receptor and the family of metabotropic glutamate receptors
    Tian, Tian; Slaughter, Slaughter

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