Dissociated dopaminergic neurons from substantia nigra zona compacta in young vats lack functional NMDA receptors

Jie Wu, L. Donald Partridge

Research output: Contribution to journalArticlepeer-review

13 Scopus citations


Glutamate-mediated excitotoxicity plays an important role in the degeneration of nigrostriatal dopamine (DA) neurons induced by 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP), although the role of the N-methyl D-aspartate (NMDA) receptor subtype in this process is still uncertain. We studied glutamate receptor subtype agonist-induced ionic currents in acutely dissociated DA-ergic neurons from the rat substantia nigra zona compacta (SNc) using the nystatin-perforated patch-clamp whole-cell recording technique. The results fall into four main categories. First, single neurons, freshly isolated from SNc, exhibited a large soma and multipolar morphology, responded to DA, and stained positively for tyrosine hydroxylase (TH). Second, rapid application of L-glutamate (> 10-5 M) induced an inward current with minimal desensitization at a clamp voltage of -60 mV. Third, kainic acid (KA) or α-amino-3-hydroxy-5-methyl-isoxazole (AMPA) induced an inward current that was similar to the glutamate-induced current while, in the same neuron, NMDA (10-4 M) failed to induce any current response in Mg2+-free solution that contained 10-5 M glycine at a clamp voltage of -60 mV. Under the same experimental conditions, NMDA induced a clear current response in isolated substantia nigra reticulata (SNr) neurons. Fourth, the specific NMDA receptor antagonist DL-2-amino-5-phosphonovaleric acid (APV, 10-4 M) failed to block 10-4 M glutamate-induced inward current, while the specific KA/AMPA receptor antagonist 6-cyano-7-nitroguinoxaline-2,3-dione (CNQX, 10-5 M) completely blocked the glutamate-induced current. These results indicate that in single SNc DAergic neurons of 2-week-old rats, L-glutamate-induced inward current is mediated by non-NMDA receptors rather than by NMDA receptors.

Original languageEnglish (US)
Pages (from-to)699-704
Number of pages6
JournalPflugers Archiv European Journal of Physiology
Issue number5
StatePublished - 1998
Externally publishedYes


  • Dopaminergic neuron
  • Glutamate
  • N-methyl-D-aspartate receptor
  • Patch-clamp
  • Substantia nigra zona compacta

ASJC Scopus subject areas

  • Physiology
  • Clinical Biochemistry
  • Physiology (medical)


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