Excitatory amino acid-evoked release of [3H]GABA from hippocampal neurons in primary culture

Katherine M. Harris, Richard J. Miller*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

65 Scopus citations


We investigated the release of γ-[2,3-3H(N)]aminobutyric acid ([3H]GABA) from hippocampal neurons in primary cell culture. [3H]GABA release was stimulated by the excitatory amino acid neurotransmitter glutamate as well as by N-methyl-D-aspartate (NMDA) and kainate. Cell depolarization induced by raising [K+]0 or by veratridine also stimulated [3H]GABA release. NMDA-induced release was completely blocked by 3-((±)-carboxypiperazin-4yl)-propyl-1-phosphonic acid (CPP+), Mg2+ and Zn2+ whereas the release induced by glutamate and kainate was much less susceptible to inhibition by these substances. Furthermore, removal of external Ca2+ inhibited NMDA-induced release, but not that induced by glutamate, kainate, veratridine or 50 mM K+. Removal of external Na+ reduced [3H]GABA release evoked by all stimuli, but to different extents. All of the excitatory amino acids tested increased [Ca2+]i within hippocampal neurons as assessed by fura-2 based microspectrofluorimetry. This increase in [Ca2+]i was completely dependent on the presence of external Ca2+. These results suggest that Ca2+-dependent and -independent forms of GABA release from hippocampal interneurons may occur. [3H]GABA release evoked by glutamate, kainate, veratridine or 50 mM K+, appeared to be mediated by the reversal of electrogenic, Na+-coupled GABA uptake. Release was inhibited by nipecotic acid, an inhibitor of the Na+-coupled GABA uptake system. However, release induced by NMDA may also include a Ca2+-dependent component.

Original languageEnglish (US)
Pages (from-to)23-33
Number of pages11
JournalBrain research
Issue number1
StatePublished - Mar 13 1989


  • Cation
  • Excitatory amino acid
  • Hippocampus
  • Primary culture
  • γ-Aminobutyric acid release

ASJC Scopus subject areas

  • Clinical Neurology
  • Molecular Biology
  • General Neuroscience
  • Developmental Biology


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