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

Abstract

We chose to examine the glutamatergic regulation of calcium currents in amphibian retinal ganglion cells. These neurons possess a plethora of glutamate receptors, including the AMPAÏkainate and NMDA ionotropic receptors (Slaughter & Miller, 1983) and at least one form of metabotropic receptor (Akopian & Witkovsky, 1996). Additionally, these neurons are thought to be purely postsynaptic in the retina and therefore ionotropic and metabotropic receptors may function in a unique manner to control postsynaptic integration rather than regulation of transmitter release. Recordings from ganglion cells revealed sustained, highvoltage-activated calcium channel currents. These currents were suppressed by both ionotropic and metabotropic glutamate agonists. Ganglion cells possessed all three groups of metabotropic receptor, although group III agonists produced the largest effect on the calcium channel. The Journal of Physiology (1998) 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 ù-conotoxin GVIAsensitive 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 (IP×) 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.7667

Slow Excitation of Cultured Rat Retinal Ganglion Cells by Activating Group I Metabotropic Glutamate Receptors

“…Group I mGluR enhancement of calcium channel activity (Rothe et al 1994) is also a possibility. There is also evidence that group I mGluR activation reduces calcium channel current in RGCs (Akopian and Witkovsky 1996; Rothe et al 1994;Shen and Slaughter 1998). Our results are not necessarily inconsistent with these observations that were done under voltage-clamp conditions.…”

Group III Metabotropic Glutamate Receptors and Exocytosed Protons Inhibit L-Type Calcium Currents in Cones But Not in Rods

“…It has been reported previously (Stella and Thoreson, 2000;Straiker and Sullivan, 2003) in large single cones of the tiger salamander retina that dopamine D 2 receptors and cannabinoid CB 1 receptors, which activate G i/o -type G-proteins, suppress I Ca by reducing cAMP levels and protein kinase A activity. It is also proposed in retinal ganglion cells that group III mGluRs activate phospholipase C via G-proteins and induce production of IP 3 and calcium release from internal stores, leading to suppression of L-type calcium channels (Shen and Slaughter, 1998). Precise identification of the signaling pathways of the mGluR modulation in cones remains to be elucidated.…”

Intensity-Dependent, Rapid Activation of Presynaptic Metabotropic Glutamate Receptors at a Central Synapse

“…The spontaneous activity was generated by excitatory glutamatergic input from bipolar cells because the ganglion cell was voltage-clamped close to the chloride reversal potential (Ϫ70 mV). Application of 10 M DHPG or 10 M DCG-IV, agents that are known to specifically activate groups I and II mGluRs in third-order cells in this preparation (Shen and Slaughter, 1998), did not significantly affect spontaneous activity ( Fig. 1 B, C).…”