Evidence that GYKI 52466, a novel non-NMDA antagonist enhances the decay of kainate-induced current in cultured chicken cortical neurons

O. Osipenko, A. Mike, A. Gyevai, E. S. Vizi

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Abstract

The effect of a novel non-competitive non-NMDA glutamate receptor antagonist, GYKI 52466 was studied on the glutamate agonist-induced currents in one month old cultured embryonal chicken brain neurons by a whole cell patch-clamp technique. AMPA, applied in different concentrations (30-1000 μM) did not evoke any current. Kainate evoked an increase of steady-state current (KA-current). NMDA induced a current with 5-10 times higher peak amplitude than KA, but GYKI 52466 failed to affect this current. It reduced the amplitude of KA-current in a concentration-dependent (1-100 μM) manner, and produced a slow decay of it. The IC50 value of GYKI 52466 against 100 μM KA was 20.4 ± 6.4 μM with a Hill coefficient of 1.12. The inhibition of KA-currents was voltage-dependent with greater inhibition between -110 to -40 mV than between -30 and +60 mV. In order to compare the effect of GYKI 52466 with a well-known competitive non-NMDA antagonist, we also studied the effect of the quinoxalinedione CNQX. When GYKI 52466 and CNQX were applied together there was only a small additive effect. Our results with GYKI 52466 on glutamate agonist-induced currents in embryonic chicken cortical neurons are similar to those observed in rat hippocampal neurons.

Original languageEnglish
Pages (from-to)257-263
Number of pages7
JournalDevelopmental Brain Research
Volume77
Issue number2
DOIs
Publication statusPublished - Feb 18 1994

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Keywords

  • Cell culture
  • Chicken cortical neuron
  • Excitatory amino acid receptor pharmacology
  • GYKI 52466
  • Non-NMDA antagonist
  • Whole-cell patch-clamp technique

ASJC Scopus subject areas

  • Developmental Neuroscience
  • Developmental Biology

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