Selective enhancement of tonic inhibition by increasing ambient GABA is insufficient to suppress excitotoxicity in hippocampal neurons

Jiann Horng Yeh, Chung Jiuan Jeng, Yi Wen Chen, Huey Min Lin, Yen Sheng Wu, Chih Yung Tang*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

5 Scopus citations

Abstract

γ-Aminobutyric acid (GABA) activates synaptic GABAA receptors to generate inhibitory postsynaptic potentials. GABA also acts on extrasynaptic GABAA receptors, resulting in tonic inhibition. The physiological role of tonic inhibition, however, remains elusive. We explored the neurophysiological significance of tonic inhibition by testing whether selective activation of extrasynaptic GABAA receptors is sufficient to curb excitotoxicity. Tonic inhibition was selectively enhanced by increasing ambient GABA. In both acute hippocampal slices and cultured hippocampal neurons, boosting tonic inhibition alone is insufficient to withstand the hyper-excitability of hippocampal neurons induced by low-magnesium (Mg 2+) baths. Furthermore, selective activation of extrasynaptic GABAA receptors resulted in no significant neuroprotective effects against glutamate or low-Mg2+-induced neuronal cell deaths. These data imply that under physiological conditions extrasynaptic GABAA receptors are optimally activated by ambient GABA and that a further increase in extracellular GABA concentration will not significantly enhance the effect of tonic inhibition on neuronal excitability.

Original languageEnglish
Pages (from-to)1417-1425
Number of pages9
JournalBiochemical and Biophysical Research Communications
Volume338
Issue number3
DOIs
StatePublished - 23 Dec 2005

Keywords

  • Cultured neuron
  • Epilepsy
  • Neuronal excitability
  • Neuroprotection
  • Patch clamp

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