Metabotropic glutamate receptor-mediated suppression of L-type calcium current in acutely isolated neocortical neurons

Abstract

1. The effects of metabotropic glutamate receptor (mGluR) stimulation on whole-cell Ca2+ currents were studied in pyramidal neurons isolated from the dorsal frontoparietal neocortex of rat. The selective mGluR agonist cis-(+/-)-1-aminocyclopentane-1,3-dicarboxylic acid [trans-ACPD (100 microM)] suppressed the peak high-threshold Ca2+ current by 21 +/- 1.7% (mean +/- SE) in 40 of 43 cells from 10- to 21-day-old rats. Consistent with previous findings for mGluR, glutamate, quisqualate, and ibotenate [but not alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA)] reduced the Ca2+ currents, and the responses were not blocked by the ionotropic glutamate receptor antagonists 6-cyano-7-nitro-quinoxaline-2,3-dione (CNQX) and DL-2-amino-5-phosphonovaleric acid (APV). EC50S for Ca2+ current suppression were 29 nM for quisqualate, 2.3 microM for glutamate, and 13 microM for trans-ACPD. 2. The low-threshold Ca2+ current was not modulated by trans-ACPD. The component of the high-threshold CA2+ current suppressed by mGluR was determined by pharmacology; the responses were not affected by omega-conotoxin GVIA but were occluded by the dihydropyridine Ca2+ antagonist nifedipine. Ca2+ tail currents prolonged by the dihydropyridine Ca2+ agonist (+)-SDZ 202-79] were suppressed by mGluR stimulation in parallel with the peak current. These findings strongly suggest that L-type Ca2+ channels are modulated by mGluR. 3. In neurons dialyzed with 100 microM guanosine 5'-(gamma-thio)triphosphate (GTP-gamma-S), Ca2+ current suppression was elicited by the first application of trans-ACPD (in 5 of 6 cells), but not by subsequent applications. Responses in neurons dialyzed with 2 mM guanosine 5'-(beta-thio)diphosphate (GDP-beta-S) were significantly smaller than controls. The results are consistent with mGluR acting via linkage to a G protein. 4. The responses to mGluR agonists were smaller when the external Ca2+ was replaced by Ba2+, indicating that some part of the mechanism underlying the current suppression is Ca2+ dependent. Because mGluR stimulates phosphoinositide turnover and release of Ca2+ from intracellular stores in other types of neurons, the possibility of released Ca2+ mediating inactivation of Ca2+ channels was considered. However, the Ca2+ current suppression was not attenuated by strong intracellular Ca2+ buffering [20 mM bis-(o-aminophenoxy)-N,N,N',N'-tetraacetic acid (BAPTA)], by dialysis with 100 microM inositol-1,4,5-triphosphate (IP3), or by external application of 1 microM thapsigargin. 5. We conclude that in neocortical neurons, one action of mGluR is to suppress the component of high-threshold Ca2+ current conducted by L-type Ca2+ channels.(ABSTRACT TRUNCATED AT 400 WORDS)

Modulation of Calcium Channels by Group I and Group II Metabotropic Glutamate Receptors in Dentate Gyrus Neurons from Patients with Temporal Lobe Epilepsy

“…We did not observe a slow mechanism for the mGluR-mediated Ca2' channel inhibition as was reported previously in rat neocortical neurons (58). Most probably this was because in the present study, Ba2" was substituted for Ca2' , which seems to suppress the slow inhibition (59).…”

Estradiol Activates Group I and II Metabotropic Glutamate Receptor Signaling, Leading to Opposing Influences on cAMP Response Element-Binding Protein

“…Previous work has shown a reduction in L-type calcium channel currents after estradiol administration in both striatal and DRG cells (Mermelstein et al, 1996;Chaban et al, 2003). Furthermore, mixed mGluR agonists reduce L-type calcium channel currents in hippocampal, neocortical, and cerebellar neurons (Sayer et al, 1992;Sahara and Westbrook, 1993;Chavis et al, 1994). Thus, as an initial foray into the signaling pathway by which estradiol and mGluR2/3 reduce L-type calcium channel-mediated CREB phosphorylation, we performed whole-cell recordings of hippocampal neurons.…”

Synaptic Control of Motoneuronal Excitability

“…Inhibition of transmitter release from presynaptic terminals may result from the reduction of presynaptic Ca 2+ influx (915). Inhibition of voltage-dependent Ca 2+ currents after mGluR activation occurs in neuronal soma (219,428,730,1089,1185,1204,1272,1410); perhaps a similar mechanism underlies the presynaptic inhibitory action of mGluR agonists. Another possible mechanism is the direct modulation of the exocytotic machinery by influencing the availability of vesicles or their probability of release (468).…”