Purinergic modulation of the excitatory synaptic input onto rat striatal neurons

Michael Tautenhahn, Anna Leichsenring, Ilenio Servettini, Michael Pesic, Beata Sperlagh, Wolfgang Nörenberg, Peter Illes

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Abstract

There is no in situ evidence hitherto for a modulation by ATP of the glutamatergic excitatory transmission onto medium spiny neurons (MSNs) in the rat striatum. In order to resolve this question, we used the patch-clamp technique in brain slice preparations to record excitatory postsynaptic currents (EPSCs) evoked by intrastriatal electrical stimulation and applied N-methyl-d-aspartate (NMDA) or α-amino-3-hydroxy-5-methyl-4- isoxazolepropionic acid (AMPA) to activate transmembrane currents of MSNs. In the absence of external Mg 2+, ATP caused a higher maximum inhibition of the EPSCs than adenosine. Only P1 (A 1), but not P2 receptor antagonists interfered with the effects of both ATP and adenosine. Moreover, A 1 receptor antagonists were less potent in blocking the inhibition by ATP than that by adenosine. Eventually, adenosine deaminase (ADA) almost abolished the adenosine-induced inhibition, but only moderately decreased the ATP-induced inhibition. Antagonists of A 1 receptors (but not of P2 receptors) counteracted the depression by ATP of the current responses to exogenous NMDA, without altering those to AMPA. It is suggested that ATP indirectly, via its degradation product adenosine, stimulates presynaptic inhibitory A 1 receptors situated at glutamatergic nerve terminals of striatal afferents; these nerve terminals are devoid of P2 receptors. However, ATP, in contrast to adenosine, also activates postsynaptic A 1 receptors at the MSN neurons themselves. The resulting negative interaction with NMDA receptors requires localized extracellular catabolism of ATP by ectonucleotidases.

Original languageEnglish
Pages (from-to)1756-1766
Number of pages11
JournalNeuropharmacology
Volume62
Issue number4
DOIs
Publication statusPublished - márc. 1 2012

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ASJC Scopus subject areas

  • Pharmacology
  • Cellular and Molecular Neuroscience

Cite this

Tautenhahn, M., Leichsenring, A., Servettini, I., Pesic, M., Sperlagh, B., Nörenberg, W., & Illes, P. (2012). Purinergic modulation of the excitatory synaptic input onto rat striatal neurons. Neuropharmacology, 62(4), 1756-1766. https://doi.org/10.1016/j.neuropharm.2011.12.001