P2Y1 receptor activation inhibits NMDA receptor-channels in layer V pyramidal neurons of the rat prefrontal and parietal cortex

Julia Luthardt, Sebestyen J. Borvendeg, Beata Sperlagh, Wolfgang Poelchen, Kerstin Wirkner, Peter Illes

Research output: Contribution to journalArticle

46 Citations (Scopus)

Abstract

In the 1st part of this study, monosynaptic excitatory postsynaptic potentials (EPSPs) in layer V of the rat prefrontal cortex (PFC) were evoked by electrical stimulation of layer I. Recordings with intracellular sharp, microelectrodes showed a concentration-dependent inhibition of the EPSP by adenosine 5′-O-(2-thiodiphosphate) (ADP-β-S). Pyridoxal-phosphate-6-azophenyl-2′,4′-disulphonic acid (PPADS), when given alone depressed the EPSP and in addition antagonized the effect of ADP-β-S. Exclusion of the N-methyl-D-aspartate (NMDA) component of the EPSP by D(·)-amino-5-phosphonopentanoic acid (AP-5) abolished the ADP-β-S-induced depression. The pressure-application of both NMDA and α-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid (AMPA) caused reproducible depolarizations. ADP-β-S inhibited the effect of NMDA, but did not alter that of AMPA. PPADS was also under these conditions antagonistic with ADP-β-S. In the 2nd part of the study, NMDA-induced currents were measured by whole-cell patch-clamp pipettes. ADP-β-S caused a concentration-dependent inhibition of the responses to NMDA. PPADS alone did not alter the NMDA-currents but again antagonized the action of ADP-β-S; 2′-deoxy-N6-methyladenosine-3′,5′-diphosphate (MRS 2179) also abolished the NMDA effect. The ADP-β-S-induced inhibition persisted in the presence of tetrodotoxin (TTX) or guanosine 5′-O-(3-thiodiphosphate) (GDP-β-S) applied to the external medium and the pipette solution, respectively. The 8-cyclopentyl-1,3-dipropylxanthine (DPCPX) moderately decreased the ADP-β-S effect. The inhibitory function of ADP-β-S on EPSPs and the interaction with PPADS was observed also in layer V pyramidal neurons of the parietal somatosensory cortex. In conclusion, metabotropic P2Y1 receptors appear to exert a new modulatory influence on fast excitatory amino acid transmission in the cerebral cortex.

Original languageEnglish
Pages (from-to)161-172
Number of pages12
JournalNeurochemistry international
Volume42
Issue number2
DOIs
Publication statusPublished - Jan 1 2003

Keywords

  • P2Y receptor activation
  • Parietal cortex
  • Pyramidal neurons

ASJC Scopus subject areas

  • Cellular and Molecular Neuroscience
  • Cell Biology

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