Group I metabotropic glutamate receptors mediate an inward current in rat substantia nigra dopamine neurons that is independent from calcium mobilization

Ezia Guatteo, Nicola B. Mercuri, Giorgio Bernardi, Thomas Knöpfel

Research output: Contribution to journalArticlepeer-review

Abstract

Metabotropic glutamate receptors modulate neuronal excitability via a multitude of mechanisms, and they have been implicated in the pathogenesis of neurodegenerative processes. Here we investigated the responses mediated by group I metabotropic glutamate receptors (mGluRs) in dopamine neurons of the rat substantia nigra pars compacta, using whole cell patch-clamp recordings in combination with microfluorometric measurements of [Ca2+](i) and [Na+](i). The selective group I mGluR agonist (S)-3,5-dihydroxyphenylglycine (3,5-DHPG) was bath-applied (20 μM, 30 s to 2 min) or applied locally by means of short-lasting (2-4 s) pressure pulses, delivered through an agonist- containing pipette positioned close to the cell body of the neuron. 3,5-DHPG evoked an inward current characterized by a transient and a sustained component, the latter of which was uncovered only with long-lasting agonist applications. The fast component coincided with a transient elevation of [Ca2+](i), whereas the total current was associated with a rise in [Na+](i). These responses were not affected either by the superfusion of ionotropic excitatory amino acid antagonists 6-cyano-7-nitroquinoxaline-2,3- dione (CNQX) and D-2-amino-5-phosphono-pentanoic acid (D-APV), nor by the sodium channel blocker tetrodotoxin (TTX). (S)-α-methyl-4-carboxyphenyl- glycine (S-MCPG) and the more selective mGluR1 antagonist 7(hydroxyimino)cyclopropa[b]chromen-1a-carboxylate (CPCCOEt) depressed both 3,5-DHPG-induced inward current components and, although less effectively, the associated [Ca2+](i) elevations. On repeated agonist applications the inward current and the calcium transients both desensitized. The time constant of recovery from desensitization differed significantly between these two responses, being 67.4 ± 4.4 s for the inward current and 28.6 ± 2.7 s for the calcium response. Bathing the tissue in a calcium-free/EGTA medium or adding thapsigargin (1 μM) to the extracellular medium prevented the generation of the [Ca2+](i) transient, but did not prevent the activation of the inward current. These electrophysiological and fluorometric results show that the 3,5-DHPG-induced inward current and the [Ca2+](i) elevations are mediated by independent pathways downstream the activation of mGluR1.

Original languageEnglish
Pages (from-to)1974-1981
Number of pages8
JournalJournal of Neurophysiology
Volume82
Issue number4
Publication statusPublished - 1999

ASJC Scopus subject areas

  • Physiology
  • Neuroscience(all)

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