Abstract
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 language | English (US) |
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Pages (from-to) | 23-33 |
Number of pages | 11 |
Journal | Brain research |
Volume | 482 |
Issue number | 1 |
DOIs | |
State | Published - Mar 13 1989 |
Keywords
- Cation
- Excitatory amino acid
- Hippocampus
- Primary culture
- γ-Aminobutyric acid release
ASJC Scopus subject areas
- Clinical Neurology
- Molecular Biology
- General Neuroscience
- Developmental Biology