The Functional Role of Spontaneously Opening GABAA Receptors in Neural Transmission

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

*Corresponding author for this work

Research output: Contribution to journalReview article

Abstract

Ionotropic type of γ-aminobutyric acid receptors (GABAARs) produce two forms of inhibitory signaling: phasic inhibition generated by rapid efflux of neurotransmitter GABA into the synaptic cleft with subsequent binding to GABAARs, and tonic inhibition generated by persistent activation of extrasynaptic and/or perisynaptic GABAARs by GABA continuously present in the extracellular space. It is widely accepted that phasic and tonic GABAergic inhibition is mediated by receptor groups of distinct subunit composition and modulated by different cytoplasmic mechanisms. Recently, however, it has been demonstrated that spontaneously opening GABAARs (s-GABAARs), which
do not need GABA binding to enter an active state, make a significant input into tonic inhibitory signaling. Due to GABA-independent action mode, s-GABAARs promise new safer options for therapy of neural disorders (such as epilepsy) devoid of side effects connected to abnormal fluctuations of GABA concentration in the brain. However, despite the potentially important role of s-GABAARs in neural signaling, they still remain out of focus of neuroscience studies, to a large extent due to technical difficulties in their experimental research. Here, we summarize present data on s-GABAARs functional properties and experimental approaches that allow isolation of s-GABAARs effects from those of conventional (GABA-dependent) GABAARs
Original languageEnglish
Article number72
Number of pages7
JournalFrontiers in Molecular Neuroscience
Volume12
Issue number72
DOIs
Publication statusPublished - 28 Mar 2019

Keywords

  • GABA-A receptor
  • GABA-independent inhibition
  • phasic conductance
  • tonic conductance
  • G-proteins

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