Properties and ionic mechanisms of a metabotropic glutamate receptor-mediated slow afterdepolarization in neocortical neurons

1994 ◽  
Vol 72 (2) ◽  
pp. 693-704 ◽  
Author(s):  
C. C. Greene ◽  
P. C. Schwindt ◽  
W. E. Crill
Keyword(s):  
Glutamate Receptor ◽  
Metabotropic Glutamate Receptors ◽  
Pyramidal Neurons ◽  
Metabotropic Glutamate Receptor ◽  
Equilibrium Potential ◽  
Cholinergic Antagonists ◽  
Recording Electrode ◽  
Metabotropic Glutamate ◽  
Ionic Mechanisms ◽  
Layer V

1. Pyramidal neurons from layer V of rat neocortex were recorded intracellularly in a brain slice preparation to study their response to stimulation of metabotropic glutamate receptors (mGluRs) by bath application of the selective mGluR agonist (1S,3R)-1-aminocyclopentane-1,3-dicarboxylic acid (1S,3R-ACPD) and by the nonselective agonists glutamate and quisqualate. 2. The principal postsynaptic effect of mGluR stimulation in the presence of ionotropic glutaminergic and muscarinic cholinergic antagonists was the appearance of a slow afterdepolarization (ADP) after evoked spikes. Only an afterhyperpolarization (AHP) was present in control perfusate. After 20 spikes evoked individually at 100 Hz the ADP peaked at 317 +/- 117 (SD) ms after the spike train, ranged from 1 to 12 mV in peak amplitude, and decayed over 7.4 +/- 4.7 s. This effect was not blocked by L-2-amino-3-phosphono-propionic acid (1 mM). Spikes evoked in the presence of the ionotropic glutamate receptor agonist R,S-alpha-amino-3-hydroxy-5-methylisoxazole-4-proprionic acid (AMPA) did not have an ADP. 3. A detectable ADP appeared at concentrations of 0.1 microM quisqualate or 0.5 microM 1S,3R-ACPD. Maximum ADP amplitude was obtained with 5 microM quisqualate or 100 microM 1S,3R-ACPD. The ADP appeared after a single evoked spike in most cells tested and ADP amplitude increased to a maximum as the number of spikes evoked at 100 Hz was increased to between 5 and 20. 4. The ionic mechanisms underlying the ADP were examined by ion substitution and the application of channel-blocking agents. No difference in ADP amplitude was observed when the recording electrode contained CH3SO4. instead of Cl.. The ADP was present after 3 mM extracellular Cs+ were added to block the hyperpolarization-activated cation current or when 100 microM Ba2+ were included to block voltage-gated K+ currents. The ADP was abolished when Mn2+ was substituted for Ca2+ in the perfusate or when the Ca2+ chelator 5,5'-dimethyl-bis-(o-aminophenoxy)-N,N,N',N'-tetraacetic acid was included in the recording electrode. A large ADP followed Ca2+ spikes evoked in the presence of 1 microM tetrodotoxin with 20 mM tetraethylammonium in the perfusate or with Cs+ substituted for K+ in the recording electrode. The amplitude of the ADP after the Ca2+ spikes was reduced by 49% when extracellular Na+ concentration was reduced from 136 to 26 mM. 5. The voltage dependence of the ADP was examined in relation to K+ equilibrium potential (EK).(ABSTRACT TRUNCATED AT 400 WORDS)

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

1992 ◽  
Vol 68 (3) ◽  
pp. 833-842 ◽  
Author(s):  
R. J. Sayer ◽  
P. C. Schwindt ◽  
W. E. Crill
Keyword(s):  
Glutamate Receptor ◽  
Pyramidal Neurons ◽  
Metabotropic Glutamate Receptor ◽  
High Threshold ◽  
External Application ◽  
Metabotropic Glutamate ◽  
Neocortical Neurons ◽  
Old Rats ◽  
Low Threshold ◽  
Ca2 Channels

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)

Suppression of the glutamate receptor delta 2 subunit produces a specific impairment in cerebellar long-term depression

1996 ◽  
Vol 76 (5) ◽  
pp. 3578-3583 ◽  
Author(s):  
A. Jeromin ◽  
R. L. Huganir ◽  
D. J. Linden
Keyword(s):  
Glutamate Receptor ◽  
Antisense Oligonucleotide ◽  
Metabotropic Glutamate Receptors ◽  
Metabotropic Glutamate Receptor ◽  
Calcium Influx ◽  
Long Term Depression ◽  
Metabotropic Glutamate ◽  
Flow Through

1. The role of the glutamate receptor subunit delta 2 in the induction of cerebellar long-term depression (LTD) was investigated by application of antisense oligonucleotides. The delta 2 subunit is selectively localized to Purkinje cells (PCs), with the highest levels being in the PC dendritic spines, where parallel fibers are received and where cerebellar LTD is expressed. 2. Immunocytochemical analysis of calbindin-positive PCs revealed that both the dendritic and somatic expression of delta 2 was reduced in antisense-but not in sense-treated cultures. An antisense oligonucleotide directed against the related subunit delta 1 did not affect the expression of delta 2 in PCs. 3. Cerebellar LTD may be reliably induced in a preparation of cultured embryonic cerebellar neurons from the mouse when parallel and climbing fiber stimulation are replaced by brief glutamate pulses and strong, direct depolarization of the PC, respectively. Application of an antisense oligonucleotide directed against delta 2 completely blocked the induction of LTD produced by glutamate/ depolarization conjunctive stimulation. A delta 2 sense oligonucleotide or an antisense oligonucleotide directed against the related delta 1 subunit had no effect. 4. The effect of the delta 2 antisense oligonucleotide was not related to attenuation of calcium influx via voltage-gated channels or calcium mobilization via metabotropic glutamate receptors, as assessed with fura-2 microfluorimetry. Current flow through alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid-receptor-associated ion channels also appeared unaltered. All three of these processes have previously been shown to be required for cerebellar LTD induction. The observation that delta 2 is involved in a metabotropic-glutamate-receptor-independent signaling pathway that is required for LTD induction supports the view that delta 2 participates in the formation of a novel postsynaptic receptor complex.

scholarly journals Physiological Evidence for Ionotropic and Metabotropic Glutamate Receptors in Rat Taste Cells

1999 ◽  
Vol 82 (5) ◽  
pp. 2061-2069 ◽  
Author(s):  
Weihong Lin ◽  
Sue C. Kinnamon
Keyword(s):  
Glutamate Receptors ◽  
Glutamate Receptor ◽  
Metabotropic Glutamate Receptors ◽  
Metabotropic Glutamate Receptor ◽  
Monosodium Glutamate ◽  
Taste Receptor ◽  
Membrane Properties ◽  
Group Iii ◽  
Metabotropic Glutamate ◽  
Taste Cells

Monosodium glutamate (MSG) elicits a unique taste in humans called umami. Recent molecular studies suggest that glutamate receptors similar to those in brain are present in taste cells, but their precise role in taste transduction remains to be elucidated. We used giga-seal whole cell recording to examine the effects of MSG and glutamate receptor agonists on membrane properties of taste cells from rat fungiform papillae. MSG (1 mM) induced three subsets of responses in cells voltage-clamped at −80 mV: a decrease in holding current (subset I), an increase in holding current (subset II), and a biphasic response consisting of an increase, followed by a decrease in holding current (subset III). Most subset II glutamate responses were mimicked by the ionotropic glutamate receptor (iGluR) agonist N-methyl-d-aspartate (NMDA). The current was potentiated by glycine and was suppressed by the NMDA receptor antagonist d(−)-2-amino-5-phosphonopentanoic acid (AP5). The group III metabotropic glutamate receptor (mGluR) agonistl-2-amino-4-phosphonobutyric acid (l-AP4) usually mimicked the subset I glutamate response. This hyperpolarizing response was suppressed by the mGluR antagonist (RS)-α-cyclopropyl-4-phosphonophenylglycine (CPPG) and by 8-bromo-cAMP, suggesting a role for cAMP in the transduction pathway. In a small subset of taste cells, l-AP4 elicited an increase in holding current, resulting in taste cell depolarization under current clamp. Taken together, our results suggest that NMDA-like receptors and at least two types of group III mGluRs are present in taste receptor cells, and these may be coactivated by MSG. Further studies are required to determine which receptors are located on the apical membrane and how they contribute to the umami taste.

scholarly journals Metabotropic glutamate receptor agonists for schizophrenia

2008 ◽  
Vol 192 (2) ◽  
pp. 86-87 ◽  
Author(s):  
Paul J. Harrison
Keyword(s):  
Glutamate Receptors ◽  
Dopamine Receptor ◽  
Glutamate Receptor ◽  
Metabotropic Glutamate Receptors ◽  
Metabotropic Glutamate Receptor ◽  
Receptor Blocking ◽  
Receptor Agonists ◽  
Metabotropic Glutamate ◽  
Glutamate Receptor Agonists

SummaryA drug acting at metabotropic glutamate receptors has recently been reported to be an effective antipsychotic, breaking the rule that only dopamine receptor-blocking drugs have this property. The finding complements accumulating evidence that glutamatergic abnormalities are important in the pathophysiology of schizophrenia.

scholarly journals Experience-Induced Arc/Arg3.1 Primes CA1 Pyramidal Neurons for Metabotropic Glutamate Receptor-Dependent Long-Term Synaptic Depression

Neuron ◽  
2013 ◽  
Vol 80 (1) ◽  
pp. 72-79 ◽  
Author(s):  
Vikram Jakkamsetti ◽  
Nien-Pei Tsai ◽  
Christina Gross ◽  
Gemma Molinaro ◽  
Katie A. Collins ◽  
...  
Keyword(s):  
Glutamate Receptor ◽  
Pyramidal Neurons ◽  
Metabotropic Glutamate Receptor ◽  
Synaptic Depression ◽  
Metabotropic Glutamate ◽  
Ca1 Pyramidal Neurons
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