Group III metabotropic glutamate receptor agonists modulate high voltage-activated Ca2+ currents in pyramidal neurons of the adult rat

Alessandro Stefani, Francesca Spadoni, Giorgio Bernardi

Research output: Contribution to journalArticle

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Abstract

In pyramidal neurons of the rat sensorimotor cortex, we have investigated the modulation of high voltage-activated calcium currents by agonists at group III metabotropic glutamate receptors (mGluRs). l-2-Amino-4-phosphonobutyrate (1-AP4) and l-serine-O-phosphate (1-SOP) reduced calcium currents in the vast majority of cells isolated from the adult animal. Interestingly, this modulation was negligible in the young animals (2-14 postnatal days), becoming prominent only after full development (more than 21 days). The efficacy of 1-SOP mimicked 1-AP4 in reducing calcium currents. Yet, l-SOP produced saturating responses at about 3 μM and significant modulation at nanomolar concentrations (EC50 = 923 nM). The voltage-dependence of the group III mGluR-mediated responses was evaluated by comparing the inhibition of 'standard' and 'facilitated' conductances. On the calcium currents facilitated by depolarizing prepulse, 3 μM l-SOP produced a mean 13.4% inhibition compared with 19.6% in control condition, supporting the proposition that part of the modulation was voltage-dependent. The calcium current inhibition caused by the activation of group III metabotropic glutamate receptors was only partially sensitive to ω-conotoxin GVIA, but largely inhibited by ω-agatoxin IVA, at concentrations (100 nM) known to block P- and Q-type channels. Conversely, the dihydropyridine antagonists nifedipine and nimodipine (50-500 nM) failed to prevent the group III mGluR-mediated response in the majority of tested cells (more than 65%). Furthermore, the long-lasting tail promoted by the inclusion of the dihydropyridine agonist Bay K 8644 was not consistently affected by 1-SOP and 1-AP4. These findings imply that the observed modulation involves different channel subtypes, namely N- and P- or Q-type channels, and suggests that group III mGluRs play an important role in the intrinsic and synaptic functions of adult cortical pyramidal neurons.

Original languageEnglish
Pages (from-to)237-244
Number of pages8
JournalExperimental Brain Research
Volume119
Issue number2
DOIs
Publication statusPublished - 1998

Fingerprint

Excitatory Amino Acid Agonists
Metabotropic Glutamate Receptors
Pyramidal Cells
Calcium
Agatoxins
Conotoxins
3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethyl-5-nitro-4-(2-(trifluoromethyl)phenyl)-, Methyl ester
Phosphoserine
Nimodipine
Nifedipine

Keywords

  • Calcium conductances
  • Development
  • l-2-amino-4-phosphonobutyrate
  • l-serine-O-phoshate
  • Neuroprotection
  • Rat

ASJC Scopus subject areas

  • Neuroscience(all)

Cite this

Group III metabotropic glutamate receptor agonists modulate high voltage-activated Ca2+ currents in pyramidal neurons of the adult rat. / Stefani, Alessandro; Spadoni, Francesca; Bernardi, Giorgio.

In: Experimental Brain Research, Vol. 119, No. 2, 1998, p. 237-244.

Research output: Contribution to journalArticle

Stefani, Alessandro ; Spadoni, Francesca ; Bernardi, Giorgio. / Group III metabotropic glutamate receptor agonists modulate high voltage-activated Ca2+ currents in pyramidal neurons of the adult rat. In: Experimental Brain Research. 1998 ; Vol. 119, No. 2. pp. 237-244.
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