PMID- 1432051
OWN - NLM
STAT- MEDLINE
DCOM- 19921127
LR  - 20171213
IS  - 0022-3077 (Print)
IS  - 0022-3077 (Linking)
VI  - 68
IP  - 3
DP  - 1992 Sep
TI  - Metabotropic glutamate receptor-mediated suppression of L-type calcium current in 
      acutely isolated neocortical neurons.
PG  - 833-42
AB  - 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)
FAU - Sayer, R J
AU  - Sayer RJ
AD  - Department of Physiology and Biophysics, University of Washington School of 
      Medicine, Seattle 98195.
FAU - Schwindt, P C
AU  - Schwindt PC
FAU - Crill, W E
AU  - Crill WE
LA  - eng
GR  - NS-16792/NS/NINDS NIH HHS/United States
GR  - NS-20482/NS/NINDS NIH HHS/United States
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PT  - Research Support, U.S. Gov't, P.H.S.
PL  - United States
TA  - J Neurophysiol
JT  - Journal of neurophysiology
JID - 0375404
RN  - 0 (Guanine Nucleotides)
RN  - 0 (Receptors, Glutamate)
RN  - 24GP945V5T (Barium)
RN  - SY7Q814VUP (Calcium)
SB  - IM
MH  - Animals
MH  - Barium/pharmacology
MH  - Calcium/*physiology
MH  - Cell Separation
MH  - Cerebral Cortex/cytology/*physiology
MH  - Differential Threshold
MH  - Electrophysiology
MH  - Guanine Nucleotides/pharmacology
MH  - Neurons/*physiology
MH  - Rats
MH  - Receptors, Glutamate/*metabolism/physiology
EDAT- 1992/09/01 00:00
MHDA- 1992/09/01 00:01
CRDT- 1992/09/01 00:00
PHST- 1992/09/01 00:00 [pubmed]
PHST- 1992/09/01 00:01 [medline]
PHST- 1992/09/01 00:00 [entrez]
AID - 10.1152/jn.1992.68.3.833 [doi]
PST - ppublish
SO  - J Neurophysiol. 1992 Sep;68(3):833-42. doi: 10.1152/jn.1992.68.3.833.