Component

Extrasynaptic GABA-A receptors mediating tonic current

Extrasynaptic GABA-A receptors mediating tonic current. Species, exposure and limitations are retained in each linked claim.

3 recorded relationships. Experimental role, claim status and evidence remain attached to each record.

Read recorded mechanisms Open recursive mind map

How nutrients influence it

Every nutrient with a recorded effect on this component, credited to the nutrient that acted rather than the chapter that recorded it. Open a nutrient to see the findings and the conditions they were measured under.

How nutrients reach it in more than one step

Chains of two or more recorded steps that end here, grouped by the nutrient they start from. Each step is a separate finding, so a chain is a route a mechanism could take, not proof that it does.

Tracing routes…

What it does

Every recorded relationship this component is part of, grouped by its role. Plain wording comes first; the technical statement follows.

Recorded relationships

What acts on it

  1. Zinc is an abundant trace metal in the hippocampus nerve terminals and blocked the GABA-evoked and ganaxolone-potentiated GABA-gated chloride currents in dentate gyrus granule cells and CA1 pyramidal cells in a concentration-dependent fashion similar to competitive GABA-A receptor antagonists, zinc completely blocked ganaxolone potentiation of extrasynaptic tonic currents but not synaptic phasic currents, systemic ganaxolone produced dose-dependent suppression of behavioral and electrographic seizures in fully-kindled mice with complete protection at 10 mg/kg, however the antiseizure effects were significantly prevented by intrahippocampal zinc with a median effective dose of 150 micromolar, and the response was reversible.

    Zinc(II) ion → Extrasynaptic GABA-A receptors mediating tonic current source_derived_draftungraded
    Experimental context and source evidence
    evidence_span
    {"source_cache": "artifacts/gaba-research/30471294.abstract.txt", "locator": "Indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "657923c781b7e3a3309235bce60303fde53f18d7a830cde050b268269f02747a", "start_char": 0, "end_char": 1814, "text_sha256": "657923c781b7e3a3309235bce60303fde53f18d7a830cde050b268269f02747a"}
    experimental_model
    Recordings of tonic and phasic currents in dissociated hippocampal neurons and slices, with a kindled seizure model
    exposure
    Zinc with the synthetic neurosteroid ganaxolone, applied to neurons and intrahippocampally in fully kindled mice
    limitations
    The separation of tonic from phasic current is what makes the subunit assignment work. Zinc was given intrahippocampally at a defined dose rather than altered nutritionally.
    nutrient_topic
    GABA research collection; topical membership is not evidence of a direct clinical effect, and the sign of a GABA response depends on the chloride gradient of the cell it was measured in. · Gamma-aminobutyric acid
    organism
    Mouse
    plain_language
    Zinc shuts down the steroid-sensitive receptors that sit outside synapses while leaving the ones inside synapses working.
    primary_references
    [gb-p30471294] Zinc reduces antiseizure activity of neurosteroids by selective blockade of extrasynaptic GABA-A receptor-mediated tonic inhibition in the hippocampus. (2019). https://pubmed.ncbi.nlm.nih.gov/30471294/ DOI: 10.1016/j.neuropharm.2018.11.031
    tissue_or_cell_type
    Dentate gyrus granule cells and CA1 pyramidal cells

    GABA: a ligand with no sign of its own, the cofactor that limits its synthesis, the barrier that keeps it out of the brain, and the immune settings where the same molecule protects and harms (2026-09-22) · lines 261–272

    AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Recordings of tonic and phasic currents in dissociated hippocampal neurons and slices, with a kindled seizure model · source_derived_draft · unverified_draft

    ### gb-zinc-blocks-only-the-tonic-receptors Zinc is an abundant trace metal in the hippocampus nerve terminals and blocked the GABA-evoked and ganaxolone-potentiated GABA-gated chloride currents in dentate gyrus granule cells and CA1 pyramidal cells in a concentration-dependent fashion similar to competitive GABA-A receptor antagonists, zinc completely blocked ganaxolone potentiation of extrasynaptic tonic currents but not synaptic phasic currents, systemic ganaxolone produced dose-dependent suppression of behavioral and electrographic seizures in fully-kindled mice with complete protection at 10 mg/kg, however the antiseizure effects were significantly prevented by intrahippocampal zinc with a median effective dose of 150 micromolar, and the response was reversible. Condition category: normal nutrient_topic: GABA research collection; topical membership is not evidence of a direct clinical effect, and the sign of a GABA response depends on the chloride gradient of the cell it was measured in. plain_language: Zinc shuts down the steroid-sensitive receptors that sit outside synapses while leaving the ones inside synapses working. organism: Mouse tissue_or_cell_type: Dentate gyrus granule cells and CA1 pyramidal cells experimental_model: Recordings of tonic and phasic currents in dissociated hippocampal neurons and slices, with a kindled seizure model limitations: The separation of tonic from phasic current is what makes the subunit assignment work. Zinc was given intrahippocampally at a defined dose rather than altered nutritionally. exposure: Zinc with the synthetic neurosteroid ganaxolone, applied to neurons and intrahippocampally in fully kindled mice evidence_span: {"source_cache": "artifacts/gaba-research/30471294.abstract.txt", "locator": "Indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "657923c781b7e3a3309235bce60303fde53f18d7a830cde050b268269f02747a", "start_char": 0, "end_char": 1814, "text_sha256": "657923c781b7e3a3309235bce60303fde53f18d7a830cde050b268269f02747a"} [gb-p30471294] Zinc reduces antiseizure activity of neurosteroids by selective blockade of extrasynaptic GABA-A receptor-mediated tonic inhibition in the hippocampus. (2019). https://pubmed.ncbi.nlm.nih.gov/30471294/ DOI: 10.1016/j.neuropharm.2018.11.031
    Complete structured claim and evidence

Where it participates (unsigned role)

  1. In two multicentre double-blind randomised placebo-controlled phase 3 trials of brexanolone injection in women with post-partum depression, the least-squares mean reduction in Hamilton Rating Scale for Depression total score at 60 hours was significantly greater with brexanolone than with placebo, the treatment was generally well tolerated and the most common adverse events included headache, dizziness and somnolence, with sedation-related events leading to dose interruption or reduction in a small number of patients.

    Brexanolone, an intravenous allopregnanolone preparation → Hamilton Rating Scale for Depression total score source_derived_draftungraded
    Experimental context and source evidence
    evidence_span
    {"source_cache": "artifacts/gaba-research/30177236.abstract.txt", "locator": "Indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "e1fe6320cb8a13ea913662a0f648ef919eecbeeb47c742242c58ed4a342b2ceb", "start_char": 0, "end_char": 4369, "text_sha256": "e1fe6320cb8a13ea913662a0f648ef919eecbeeb47c742242c58ed4a342b2ceb"}
    experimental_model
    Two multicentre double-blind randomised placebo-controlled trials of a 60-hour intravenous infusion
    exposure
    Brexanolone, an intravenous formulation of the endogenous neurosteroid allopregnanolone, in severe and moderate postpartum depression
    limitations
    Two randomised trials with a depression rating scale as the endpoint over 60 hours of infusion, in a hospital setting.
    nutrient_topic
    GABA research collection; topical membership is not evidence of a direct clinical effect, and the sign of a GABA response depends on the chloride gradient of the cell it was measured in. · Gamma-aminobutyric acid
    organism
    Human
    plain_language
    An infusion of the body own calming steroid lifted depression scores within sixty hours.
    primary_references
    [gb-p30177236] Brexanolone injection in post-partum depression: two multicentre, double-blind, randomised, placebo-controlled, phase 3 trials. (2018). https://pubmed.ncbi.nlm.nih.gov/30177236/ DOI: 10.1016/s0140-6736(18)31551-4
    tissue_or_cell_type
    Central nervous system

    GABA: a ligand with no sign of its own, the cofactor that limits its synthesis, the barrier that keeps it out of the brain, and the immune settings where the same molecule protects and harms (2026-09-22) · lines 313–324

    AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Two multicentre double-blind randomised placebo-controlled trials of a 60-hour intravenous infusion · source_derived_draft · unverified_draft

    ### gb-a-neurosteroid-works-in-postpartum-depression In two multicentre double-blind randomised placebo-controlled phase 3 trials of brexanolone injection in women with post-partum depression, the least-squares mean reduction in Hamilton Rating Scale for Depression total score at 60 hours was significantly greater with brexanolone than with placebo, the treatment was generally well tolerated and the most common adverse events included headache, dizziness and somnolence, with sedation-related events leading to dose interruption or reduction in a small number of patients. Condition category: normal nutrient_topic: GABA research collection; topical membership is not evidence of a direct clinical effect, and the sign of a GABA response depends on the chloride gradient of the cell it was measured in. plain_language: An infusion of the body own calming steroid lifted depression scores within sixty hours. organism: Human tissue_or_cell_type: Central nervous system experimental_model: Two multicentre double-blind randomised placebo-controlled trials of a 60-hour intravenous infusion limitations: Two randomised trials with a depression rating scale as the endpoint over 60 hours of infusion, in a hospital setting. exposure: Brexanolone, an intravenous formulation of the endogenous neurosteroid allopregnanolone, in severe and moderate postpartum depression evidence_span: {"source_cache": "artifacts/gaba-research/30177236.abstract.txt", "locator": "Indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "e1fe6320cb8a13ea913662a0f648ef919eecbeeb47c742242c58ed4a342b2ceb", "start_char": 0, "end_char": 4369, "text_sha256": "e1fe6320cb8a13ea913662a0f648ef919eecbeeb47c742242c58ed4a342b2ceb"} [gb-p30177236] Brexanolone injection in post-partum depression: two multicentre, double-blind, randomised, placebo-controlled, phase 3 trials. (2018). https://pubmed.ncbi.nlm.nih.gov/30177236/ DOI: 10.1016/s0140-6736(18)31551-4
    Complete structured claim and evidence

  2. We examined in encephalitogenic T cells if they expressed functional GABA channels that could be activated by the low nanomolar to 1 micromolar physiological concentrations of GABA present around neurons in the brain, the cells expressed the alpha1, alpha4, beta2, beta3, gamma1 and delta GABA-A channel subunits and formed functional extrasynaptic-like GABA channels that were activated by 1 micromolar GABA, and 100 nanomolar and higher GABA concentrations decreased T cell proliferation.

    Gamma-aminobutyric acid → T-cell proliferation, model specified source_derived_draftungraded
    Experimental context and source evidence
    evidence_span
    {"source_cache": "artifacts/gaba-research/18954912.abstract.txt", "locator": "Indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "3723b5b4b643817af252230d67dafbc0b5ca2deadb17cdbdbc9f340ddfc6a472", "start_char": 0, "end_char": 728, "text_sha256": "3723b5b4b643817af252230d67dafbc0b5ca2deadb17cdbdbc9f340ddfc6a472"}
    experimental_model
    Patch clamp and proliferation assays on encephalitogenic T cells at physiological GABA concentrations
    exposure
    GABA at nanomolar to micromolar concentrations, the range present around neurons
    limitations
    A small subunit and function study in one T cell type. It measures the concentration range that matters rather than assuming it.
    nutrient_topic
    GABA research collection; topical membership is not evidence of a direct clinical effect, and the sign of a GABA response depends on the chloride gradient of the cell it was measured in. · Gamma-aminobutyric acid
    organism
    Rat
    plain_language
    These cells carry the kind of channel built for a steady background level rather than a synaptic pulse, and that background level slows them down.
    primary_references
    [gb-p18954912] GABA, a natural immunomodulator of T lymphocytes. (2008). https://pubmed.ncbi.nlm.nih.gov/18954912/ DOI: 10.1016/j.jneuroim.2008.08.017
    tissue_or_cell_type
    Encephalitogenic T cell

    GABA: a ligand with no sign of its own, the cofactor that limits its synthesis, the barrier that keeps it out of the brain, and the immune settings where the same molecule protects and harms (2026-09-22) · lines 508–519

    AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Patch clamp and proliferation assays on encephalitogenic T cells at physiological GABA concentrations · source_derived_draft · unverified_draft

    ### gb-t-cells-read-ambient-gaba We examined in encephalitogenic T cells if they expressed functional GABA channels that could be activated by the low nanomolar to 1 micromolar physiological concentrations of GABA present around neurons in the brain, the cells expressed the alpha1, alpha4, beta2, beta3, gamma1 and delta GABA-A channel subunits and formed functional extrasynaptic-like GABA channels that were activated by 1 micromolar GABA, and 100 nanomolar and higher GABA concentrations decreased T cell proliferation. Condition category: normal nutrient_topic: GABA research collection; topical membership is not evidence of a direct clinical effect, and the sign of a GABA response depends on the chloride gradient of the cell it was measured in. plain_language: These cells carry the kind of channel built for a steady background level rather than a synaptic pulse, and that background level slows them down. organism: Rat tissue_or_cell_type: Encephalitogenic T cell experimental_model: Patch clamp and proliferation assays on encephalitogenic T cells at physiological GABA concentrations limitations: A small subunit and function study in one T cell type. It measures the concentration range that matters rather than assuming it. exposure: GABA at nanomolar to micromolar concentrations, the range present around neurons evidence_span: {"source_cache": "artifacts/gaba-research/18954912.abstract.txt", "locator": "Indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "3723b5b4b643817af252230d67dafbc0b5ca2deadb17cdbdbc9f340ddfc6a472", "start_char": 0, "end_char": 728, "text_sha256": "3723b5b4b643817af252230d67dafbc0b5ca2deadb17cdbdbc9f340ddfc6a472"} [gb-p18954912] GABA, a natural immunomodulator of T lymphocytes. (2008). https://pubmed.ncbi.nlm.nih.gov/18954912/ DOI: 10.1016/j.jneuroim.2008.08.017
    Complete structured claim and evidence

In the sources

Preserved passages that mention this component, quoted exactly. Open one to read it in context.

    This is a research prototype built from draft material. It is not medical advice, and its statements still await verification against the original studies.

    Evidence, AI assistance and curation standards