The Functional Role of Spontaneously Opening GABAA Receptors in Neural Transmission
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 extrasynap...
| Main Authors: | , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Frontiers Media S.A.
2019-03-01
|
| Series: | Frontiers in Molecular Neuroscience |
| Subjects: | |
| Online Access: | https://www.frontiersin.org/article/10.3389/fnmol.2019.00072/full |
| _version_ | 1831677851300003840 |
|---|---|
| author | Nathanael O’Neill Sergiy Sylantyev |
| author_facet | Nathanael O’Neill Sergiy Sylantyev |
| author_sort | Nathanael O’Neill |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-12-20T04:48:19Z |
| format | Article |
| id | doaj.art-d94a1d5e740d44e5922beced84000e40 |
| institution | Directory Open Access Journal |
| issn | 1662-5099 |
| language | English |
| last_indexed | 2024-12-20T04:48:19Z |
| publishDate | 2019-03-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Molecular Neuroscience |
| spelling | doaj.art-d94a1d5e740d44e5922beced84000e402022-12-21T19:52:55ZengFrontiers Media S.A.Frontiers in Molecular Neuroscience1662-50992019-03-011210.3389/fnmol.2019.00072449596The Functional Role of Spontaneously Opening GABAA Receptors in Neural TransmissionNathanael O’NeillSergiy SylantyevIonotropic 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.https://www.frontiersin.org/article/10.3389/fnmol.2019.00072/fullGABA-A receptorGABA-independent inhibitionphasic conductancetonic conductanceG-proteins |
| spellingShingle | Nathanael O’Neill Sergiy Sylantyev The Functional Role of Spontaneously Opening GABAA Receptors in Neural Transmission Frontiers in Molecular Neuroscience GABA-A receptor GABA-independent inhibition phasic conductance tonic conductance G-proteins |
| title | The Functional Role of Spontaneously Opening GABAA Receptors in Neural Transmission |
| title_full | The Functional Role of Spontaneously Opening GABAA Receptors in Neural Transmission |
| title_fullStr | The Functional Role of Spontaneously Opening GABAA Receptors in Neural Transmission |
| title_full_unstemmed | The Functional Role of Spontaneously Opening GABAA Receptors in Neural Transmission |
| title_short | The Functional Role of Spontaneously Opening GABAA Receptors in Neural Transmission |
| title_sort | functional role of spontaneously opening gabaa receptors in neural transmission |
| topic | GABA-A receptor GABA-independent inhibition phasic conductance tonic conductance G-proteins |
| url | https://www.frontiersin.org/article/10.3389/fnmol.2019.00072/full |
| work_keys_str_mv | AT nathanaeloneill thefunctionalroleofspontaneouslyopeninggabaareceptorsinneuraltransmission AT sergiysylantyev thefunctionalroleofspontaneouslyopeninggabaareceptorsinneuraltransmission AT nathanaeloneill functionalroleofspontaneouslyopeninggabaareceptorsinneuraltransmission AT sergiysylantyev functionalroleofspontaneouslyopeninggabaareceptorsinneuraltransmission |