Interaction between P2Y and NMDA receptors in layer V pyramidal neurons of the rat prefrontal cortex

Kerstin Wirkner, L. Köles, Susanne Thümmler, Julia Luthardt, Wolfgang Poelchen, Heike Franke, S. Fürst, Peter Illes

Research output: Contribution to journalArticle

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Abstract

In the first part of this study, monosynaptic excitatory postsynaptic potentials (EPSPs) in layer V of the rat prefrontal cortex were evoked by electrical stimulation of layer I. Recordings by intracellular sharp microelectrodes showed that EPSPs were concentration-dependently facilitated by the P2 receptor antagonistic ATP analogue 2-methylthio ATP (2-MeSATP), while ATP itself depressed the synaptic potentials. The inhibitory effect of ATP turned into facilitation in the presence of the adenosine A1 receptor antagonist DPCPX. The 2-MeSATP-induced potentiation of EPSP amplitudes were prevented by the P2 receptor antagonists PPADS and Suramin. The EPSP was almost abolished by coapplication of the NMDA receptor antagonist AP-5 and the AMPA/kainate receptor antagonist CNQX. After blockade of the NMDA receptor-mediated part of the EPSP by AP-5, the stimulatory effect of 2-MeSATP disappeared. When NMDA or AMPA were pressure-applied onto pyramidal cells, only the NMDA-induced depolarization was potentiated by 2-MeSATP. In the second part of the study, NMDA-induced currents were measured by whole-cell patch-clamp pipettes. ATP, 2-MeSATP, UDP and UTP potentiated the response to NMDA, while ADP-β-S was inactive. PPADS antagonized the effect of ATP. Synaptic isolation of pyramidal neurons by a Ca2+-free medium or tetrodotoxin did not alter the effect of ATP which, however, was markedly depressed when GTP in the micropipette was replaced by GDP-β-S. These observations suggest that in layer V pyramidal neurons of the prefrontal cortex postsynaptically localized P2Y receptors interact with NMDA receptor-channels.

Original languageEnglish
Pages (from-to)476-488
Number of pages13
JournalNeuropharmacology
Volume42
Issue number4
DOIs
Publication statusPublished - 2002

Fingerprint

Pyramidal Cells
Prefrontal Cortex
N-Methyl-D-Aspartate Receptors
Excitatory Postsynaptic Potentials
N-Methylaspartate
Adenosine Triphosphate
Adenosine A1 Receptor Antagonists
6-Cyano-7-nitroquinoxaline-2,3-dione
Purinergic P2 Receptors
Kainic Acid Receptors
Suramin
Synaptic Potentials
Uridine Triphosphate
alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid
Uridine Diphosphate
AMPA Receptors
Tetrodotoxin
Microelectrodes
Guanosine Triphosphate
Electric Stimulation

Keywords

  • Intracellular recording
  • NMDA receptor
  • P2 receptor
  • Prefrontal cortex
  • Synaptic transmission
  • Voltage-clamp recording

ASJC Scopus subject areas

  • Cellular and Molecular Neuroscience
  • Drug Discovery
  • Pharmacology

Cite this

Interaction between P2Y and NMDA receptors in layer V pyramidal neurons of the rat prefrontal cortex. / Wirkner, Kerstin; Köles, L.; Thümmler, Susanne; Luthardt, Julia; Poelchen, Wolfgang; Franke, Heike; Fürst, S.; Illes, Peter.

In: Neuropharmacology, Vol. 42, No. 4, 2002, p. 476-488.

Research output: Contribution to journalArticle

Wirkner, Kerstin ; Köles, L. ; Thümmler, Susanne ; Luthardt, Julia ; Poelchen, Wolfgang ; Franke, Heike ; Fürst, S. ; Illes, Peter. / Interaction between P2Y and NMDA receptors in layer V pyramidal neurons of the rat prefrontal cortex. In: Neuropharmacology. 2002 ; Vol. 42, No. 4. pp. 476-488.
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AU - Fürst, S.

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