Inhibition of calcium channels in rat CA3 pyramidal neurons by a metabotropic glutamate receptor

Abstract

L-Glutamate rapidly and reversibly suppressed Ca channel current in freshly dissociated pyramidal neurons from the CA3 region of the rat hippocampus. L-Glutamate inhibition of Ca channel current could be distinguished from activation of background conductance by appropriate ionic conditions and by distinct pharmacological profiles. Ca channel inhibition by glutamate was mimicked by quisqualate, ibotenate, racemïct-ACPD and 1S,3R-ACPD but not by kainate, AMPA, L-aspartate, NMDA, L-2-amino-4-phosphonobutyric acid, or 1R,3S-ACPD; 6-cyano-7-nitroquinoxaline-2,3-dione did not inhibit the response. All agonists inhibited a similar fraction of high-voltage-activated Ca channel current, typically approximately 30%. Concentration-response relations for the agonists were consistent with mediation by a metabotropic glutamate receptor. The stereospecific agonist 1S,3R-ACPD was especially useful since it did not activate background conductances. The fraction of Ca channel current sensitive to 1S,3R-ACPD was partially blocked by omega-conotoxin GVIA but was not sensitive to dihydropyridine antagonists or agonists. The suppression of Ca channels by 1S,3R-ACPD became irreversible when cells were dialyzed with GTP-gamma-S. 1S,3R-ACPD suppressed Ca channel currents in outside-out membrane patches but not in cell-attached patches when applied outside the patch. These results suggest that metabotropic glutamate receptors suppress the activity of N-type Ca channels in CA3 neurons by a mechanism involving G-proteins but not readily diffusible second messengers.

Neural functions of calcineurin in synaptic plasticity and memory: Figure 1.

“…Activation of mGluR5 induces phosphatidylinositol hydrolysis via phospholipase C, which releases intracellular IP3-sensitive Ca 2+ stores. It further activates ryanodine-sensitive Ca 2+ stores and alters the activity of different voltage-gated channels (Gerber et al 1992;Swartz and Bean 1992;Fagni et al 2000;Sanchez-Prieto et al 2004;Park et al 2010;Zheng and Raman 2011). Additionally, mGluR5 activation enhances glutamate-evoked currents through the NMDA receptor (Fitzjohn et al 1996).…”

Presynaptic group I metabotropic glutamate receptors modulate synaptic transmission in the rat superior colliculus via 4‐AP sensitive K+ channels

“…This suggests that presynaptic N-type VDCCs are unlikely to be a major target of DHPG action in the SC, in contrast to other preparations (e.g. Swartz & Bean, 1992). For the reduction in inhibitory DHPG action observed in the presence of the L-type VDCC antagonist nifedipine, we suggest this to be caused by an indirect modulation.…”

“…Taken together, these data suggest that N-type VDCCs are crucial for presynaptic glutamate release, but the inhibitory action of DHPG is not mediated via this route, in contrast to other brain regions where CTX-sensitive VDCCs were identified as the target for inhibition by mGluR agonists (Swartz & Bean, 1992;Glaum & Miller, 1995). L-type VDCCs on the other hand appear to contribute to the action of DHPG.…”

Metabotropic Glutamate Receptor Activation Modulates Kainate and Serotonin Calcium Response in Astrocytes

“…mGluRs have been shown in neurons to modulate potassium channel function (Gerber and Gähwiler, 1994) and calcium channel currents (Sahara and Westbrook, 1993;Chavis et al, 1995). This interaction is sometimes sensitive to G-protein inhibitors such as PTx but not to second messenger blockade, raising the possibility of a direct action of the G-protein in neurons (Lester and Jahr, 1990;Swartz and Bean, 1992;Chavis et al, 1994;Ikeda et al, 1995;Choi and Lovinger, 1996).…”