Modulation of NMDA receptor current in layer V pyramidal neurons of the rat prefrontal cortex by P2Y receptor activation

Kerstin Wirkner, Albrecht Günther, Marco Weber, Segundo J. Guzman, Thomas Krause, Jochen Fuchs, L. Köles, Wolfgang Nörenberg, Peter Illes

Research output: Contribution to journalArticle

34 Citations (Scopus)

Abstract

Current responses to N-methyl-D-aspartate (NMDA) in layer V pyramidal neurons of the rat prefrontal cortex were potentiated by the P2 receptor agonists adenosine 5′-triphosphate (ATP) and uridine 5′-triphosphate (UTP). The failure of these nucleotides to induce inward current on fast local superfusion suggested the activation of P2Y rather than P2X receptors. The potentiation by ATP persisted in a Ca2+-free superfusion medium but was abolished by 1,2-bis(2-amino-5-fluorophenoxy)ethane-N,N,N′,N′- tetraacetic acid tetrakis(acetoxymethyl) ester, cyclopiazonic acid, 7-nitroindazole, fluoroacetic acid, bafilomycin, and tetanus toxin, indicating that an astrocytic signaling molecule may participate. Because the metabotropic glutamate receptor (mGluR) agonists (1S,3R)-1-aminocyclopentane-1,3-dicarboxylic acid (ACPD) (group I/II) and (RS)-3,5-dihydroxyphenylglycine (group I) both imitated the effect of ATP and the group I mGluR antagonist 1-aminoindan-1,5- dicarboxylic acid or a combination of selective mGluR1 (7-(hydroxyimino)-cyclopropa[b]chromen-1a-carboxylate) and mGluR5 (2-methyl-6-(phenylethynyl)pyridine) antagonists abolished the facilitation by ATP, it was concluded that the signaling molecule may be glutamate. Pharmacological tools known to interfere with the transduction cascade of type I mGluRs (guanosine 5′-O-(3-thiodiphosphate), U-73122, xestospongin C, 1,2-bis(2-aminophenoxy)ethane-N,N,N′,N′-tetraacetic acid, calmodulin kinase II [CAMKII] inhibitor peptide) depressed the actions of both ATP and ACPD. Characterization of the P2Y receptor by agonists (ATP and UTP), antagonists (suramin and pyridoxal-phosphate-6-azophenyl-2′,4′- disulfonic acid), and knockout mice (P2Y2 -/-) suggested that the nucleotides act at the P2Y4 subtype. In conclusion, we propose that exogenous and probably also endogenous ATP release vesicular glutamate from astrocytes by P2Y4 receptor activation. This glutamate then stimulates type I mGluRs of layer V pyramidal neurons and via the G q/phospholipase C/inositol 1,4,5-trisphosphate/Ca2+/CAMKII transduction pathway facilitates NMDA receptor currents.

Original languageEnglish
Pages (from-to)621-631
Number of pages11
JournalCerebral Cortex
Volume17
Issue number3
DOIs
Publication statusPublished - Mar 2007

Fingerprint

Pyramidal Cells
Prefrontal Cortex
N-Methyl-D-Aspartate Receptors
Adenosine Triphosphate
Glutamic Acid
Calcium-Calmodulin-Dependent Protein Kinases
Uridine Triphosphate
Ethane
Acids
Nucleotides
Tetanus Toxin
Excitatory Amino Acid Agonists
Suramin
Excitatory Amino Acid Antagonists
Dicarboxylic Acids
Metabotropic Glutamate Receptors
Pyridoxal Phosphate
Inositol 1,4,5-Trisphosphate
Guanosine
Type C Phospholipases

Keywords

  • Astrocyte
  • NMDA receptor
  • P2 receptor
  • Pyramidal neuron
  • Rat prefrontal cortex

ASJC Scopus subject areas

  • Neuroscience(all)

Cite this

Wirkner, K., Günther, A., Weber, M., Guzman, S. J., Krause, T., Fuchs, J., ... Illes, P. (2007). Modulation of NMDA receptor current in layer V pyramidal neurons of the rat prefrontal cortex by P2Y receptor activation. Cerebral Cortex, 17(3), 621-631. https://doi.org/10.1093/cercor/bhk012

Modulation of NMDA receptor current in layer V pyramidal neurons of the rat prefrontal cortex by P2Y receptor activation. / Wirkner, Kerstin; Günther, Albrecht; Weber, Marco; Guzman, Segundo J.; Krause, Thomas; Fuchs, Jochen; Köles, L.; Nörenberg, Wolfgang; Illes, Peter.

In: Cerebral Cortex, Vol. 17, No. 3, 03.2007, p. 621-631.

Research output: Contribution to journalArticle

Wirkner, K, Günther, A, Weber, M, Guzman, SJ, Krause, T, Fuchs, J, Köles, L, Nörenberg, W & Illes, P 2007, 'Modulation of NMDA receptor current in layer V pyramidal neurons of the rat prefrontal cortex by P2Y receptor activation', Cerebral Cortex, vol. 17, no. 3, pp. 621-631. https://doi.org/10.1093/cercor/bhk012
Wirkner, Kerstin ; Günther, Albrecht ; Weber, Marco ; Guzman, Segundo J. ; Krause, Thomas ; Fuchs, Jochen ; Köles, L. ; Nörenberg, Wolfgang ; Illes, Peter. / Modulation of NMDA receptor current in layer V pyramidal neurons of the rat prefrontal cortex by P2Y receptor activation. In: Cerebral Cortex. 2007 ; Vol. 17, No. 3. pp. 621-631.
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AU - Günther, Albrecht

AU - Weber, Marco

AU - Guzman, Segundo J.

AU - Krause, Thomas

AU - Fuchs, Jochen

AU - Köles, L.

AU - Nörenberg, Wolfgang

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KW - P2 receptor

KW - Pyramidal neuron

KW - Rat prefrontal cortex

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