Feature Article: Selective modulation of tonically active GABAA receptor functional subgroups by G-proteins and protein kinase C

Nathanael O’Neill, Sergiy Sylantyev* (Corresponding Author)

*Corresponding author for this work

Research output: Contribution to journalArticle

1 Citation (Scopus)

Abstract

Ionotropic receptors of γ-aminobutyric acid (GABAARs) produce two forms of inhibitory signaling: phasic inhibition triggered by activation of synaptic GABAARs at GABAergic synapses, and tonic inhibition generated in large part through persistent activation of extrasynaptic GABAARs. It has recently been demonstrated that tonic inhibition may also involve spontaneously opening GABAARs (s-GABAARs) whose activation does not require binding of γ-aminobutyric acid (GABA). Here, we examine intracellular mechanisms modulating GABAARs’ tonic effects in rat dentate gyrus granule cells (DGCs). Cellular control of s-GABAARs-delivered tonic current appears to involve signaling inputs from G-protein-dependent and -independent molecular cascades, whereas tonic GABA-dependent current in DGCs is regulated by protein kinase C. The intracellular agents that modulate s-GABAAR-generated inhibition could thus represent a generic mechanism controlling signal integration in central neural circuits.
Original languageEnglish
Pages (from-to)1046-1055
Number of pages10
JournalExperimental Biology and Medicine
Volume243
Issue number13
Early online date11 Sep 2018
DOIs
Publication statusPublished - 11 Sep 2018

Keywords

  • Spontaneously opening GABAA receptors
  • tonic inhibitory current
  • action potential generation
  • G-proteins
  • Protein Kinase C

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