G-protein-gated inwardly rectifying potassium (GIRK) channels

evidence_span

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experimental_model

Heterologous expression and immunoprecipitation of two GABA-B polypeptides with potassium channel readout

exposure

GABA-B R1 and R2 expressed alone and together, with GIRK-type potassium channel activity as the readout

limitations

Heterologous expression. The functional claim rests on channel activation in transfected cells rather than in native tissue.

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 and human genes

plain_language

Two proteins that each do almost nothing on their own make a working receptor only when put together.

primary_references

[gb-p9872315] GABA(B) receptors function as a heteromeric assembly of the subunits GABA(B)R1 and GABA(B)R2. (1998). https://pubmed.ncbi.nlm.nih.gov/9872315/ DOI: 10.1038/25348

tissue_or_cell_type

Transfected cells and neurons

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 274–285

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Heterologous expression and immunoprecipitation of two GABA-B polypeptides with potassium channel readout · source_derived_draft · unverified_draft

### gb-neither-half-works-alone Cells heterologously expressing the cloned DNA encoding the GABA-B R1 protein exhibit high-affinity antagonist-binding sites but produce little of the functional activity expected from studies of endogenous GABA-B receptors in the brain, neither GABA-B R1 nor GABA-B R2 when expressed individually activates GIRK-type potassium channels, however the combination of the two confers robust stimulation of channel activity, both genes are co-expressed in individual neurons and both proteins co-localize in transfected cells, and immunoprecipitation indicates that the two polypeptides associate with each other probably as heterodimers. 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: Two proteins that each do almost nothing on their own make a working receptor only when put together. organism: Rat and human genes tissue_or_cell_type: Transfected cells and neurons experimental_model: Heterologous expression and immunoprecipitation of two GABA-B polypeptides with potassium channel readout limitations: Heterologous expression. The functional claim rests on channel activation in transfected cells rather than in native tissue. exposure: GABA-B R1 and R2 expressed alone and together, with GIRK-type potassium channel activity as the readout evidence_span: {"source_cache": "artifacts/gaba-research/9872315.abstract.txt", "locator": "Indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "c6687fd9eb8b7ebcc0496a2385b0201b02662a5fe8da87a0089650a150f00613", "start_char": 0, "end_char": 1473, "text_sha256": "c6687fd9eb8b7ebcc0496a2385b0201b02662a5fe8da87a0089650a150f00613"} [gb-p9872315] GABA(B) receptors function as a heteromeric assembly of the subunits GABA(B)R1 and GABA(B)R2. (1998). https://pubmed.ncbi.nlm.nih.gov/9872315/ DOI: 10.1038/25348

evidence_span

{"source_cache": "artifacts/gaba-research/9872317.abstract.txt", "locator": "Indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "6a3eefc95d36d31151d094326c5d7f6dedd19b335dee29442de15b4b37ad9cfb", "start_char": 0, "end_char": 1620, "text_sha256": "6a3eefc95d36d31151d094326c5d7f6dedd19b335dee29442de15b4b37ad9cfb"}

experimental_model

Cloning of a second GABA-B subtype with binding potency and Kir3 channel coupling

exposure

GABA-B R1a, R1b and R2 expressed alone and in combination

limitations

A companion study reaching the same conclusion by a different route, including colocalisation at dendritic spines in vivo.

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

Put the two subunits together and the receptor not only works but binds its agonist far better than either part did.

primary_references

[gb-p9872317] GABA(B)-receptor subtypes assemble into functional heteromeric complexes. (1998). https://pubmed.ncbi.nlm.nih.gov/9872317/ DOI: 10.1038/25360

tissue_or_cell_type

Transfected cells and dendritic spines

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 287–298

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Cloning of a second GABA-B subtype with binding potency and Kir3 channel coupling · source_derived_draft · unverified_draft

### gb-the-pair-binds-better-than-either A new GABA-B receptor subtype GABA-B R2 does not bind available GABA-B antagonists with measurable potency, GABA-B R1a, R1b and R2 alone do not activate Kir3-type potassium channels efficiently but co-expression yields a robust coupling to activation of Kir3 channels, there is evidence for assembly of heteromeric GABA-B receptors in vivo with the proteins immunoprecipitating and localizing together at dendritic spines, and the heteromeric receptor complexes exhibit a significant increase in agonist- and partial-agonist-binding potencies as compared with individual receptors and probably represent the predominant native GABA-B receptor. 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: Put the two subunits together and the receptor not only works but binds its agonist far better than either part did. organism: Rat tissue_or_cell_type: Transfected cells and dendritic spines experimental_model: Cloning of a second GABA-B subtype with binding potency and Kir3 channel coupling limitations: A companion study reaching the same conclusion by a different route, including colocalisation at dendritic spines in vivo. exposure: GABA-B R1a, R1b and R2 expressed alone and in combination evidence_span: {"source_cache": "artifacts/gaba-research/9872317.abstract.txt", "locator": "Indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "6a3eefc95d36d31151d094326c5d7f6dedd19b335dee29442de15b4b37ad9cfb", "start_char": 0, "end_char": 1620, "text_sha256": "6a3eefc95d36d31151d094326c5d7f6dedd19b335dee29442de15b4b37ad9cfb"} [gb-p9872317] GABA(B)-receptor subtypes assemble into functional heteromeric complexes. (1998). https://pubmed.ncbi.nlm.nih.gov/9872317/ DOI: 10.1038/25360

evidence_span

{"source_cache": "artifacts/acetate-research/12496283.abstract.txt", "locator": "Indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "83f7777cab02a7c69f063d21e26f895884724f46ad539ebc767d9e6f371bf64f", "start_char": 0, "end_char": 1291, "text_sha256": "83f7777cab02a7c69f063d21e26f895884724f46ad539ebc767d9e6f371bf64f"}

experimental_model

Ligand bank screening in yeast, confirmed by calcium mobilisation, GTP-gamma-S binding and oocyte coexpression

exposure

Short chain carboxylic acid anions applied to recombinant GPR41 and GPR43

limitations

The deorphanising paper. Potencies come from recombinant systems, not from tissue, and the authors state plainly that the cognate physiological ligands are not clear.

nutrient_topic

Acetic acid research collection; topical membership is not evidence of a direct clinical effect, and the ingested acid is recorded separately from the circulating acetate anion. · Acetic acid

organism

Human and mouse receptors

plain_language

Acetate is not only fuel; it is the signal that identified this receptor.

primary_references

[acetate-p12496283] The Orphan G protein-coupled receptors GPR41 and GPR43 are activated by propionate and other short chain carboxylic acids. (2003). https://pubmed.ncbi.nlm.nih.gov/12496283/ DOI: 10.1074/jbc.m211609200

tissue_or_cell_type

Transfected mammalian cells and Xenopus oocytes

Acetic acid: the ingested acid, the receptors acetate binds, the acetyl-CoA it becomes, and the acetyl groups that reach histones (2026-09-21) · lines 225–236

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Ligand bank screening in yeast, confirmed by calcium mobilisation, GTP-gamma-S binding and oocyte coexpression · source_derived_draft · unverified_draft

### acetate-acetate-activates-ffar2 The acetate anion was identified as an agonist of human GPR43 during ligand bank screening in yeast and confirmed after transient transfection using calcium mobilisation and GTP-gamma-S binding assays and by coexpression with GIRK potassium channels in Xenopus oocytes, with formate, propionate, butyrate and pentanoate also showing agonist activity. Condition category: normal nutrient_topic: Acetic acid research collection; topical membership is not evidence of a direct clinical effect, and the ingested acid is recorded separately from the circulating acetate anion. plain_language: Acetate is not only fuel; it is the signal that identified this receptor. organism: Human and mouse receptors tissue_or_cell_type: Transfected mammalian cells and Xenopus oocytes experimental_model: Ligand bank screening in yeast, confirmed by calcium mobilisation, GTP-gamma-S binding and oocyte coexpression limitations: The deorphanising paper. Potencies come from recombinant systems, not from tissue, and the authors state plainly that the cognate physiological ligands are not clear. exposure: Short chain carboxylic acid anions applied to recombinant GPR41 and GPR43 evidence_span: {"source_cache": "artifacts/acetate-research/12496283.abstract.txt", "locator": "Indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "83f7777cab02a7c69f063d21e26f895884724f46ad539ebc767d9e6f371bf64f", "start_char": 0, "end_char": 1291, "text_sha256": "83f7777cab02a7c69f063d21e26f895884724f46ad539ebc767d9e6f371bf64f"} [acetate-p12496283] The Orphan G protein-coupled receptors GPR41 and GPR43 are activated by propionate and other short chain carboxylic acids. (2003). https://pubmed.ncbi.nlm.nih.gov/12496283/ DOI: 10.1074/jbc.m211609200

evidence_span

{"source_cache": "artifacts/alcohol-research/19561601.abstract.txt", "locator": "Indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "6aa4c10bd615439d1b5e008da1031a4ed244aeef6a0be4764930a7f183778428", "start_char": 0, "end_char": 1103, "text_sha256": "6aa4c10bd615439d1b5e008da1031a4ed244aeef6a0be4764930a7f183778428"}

experimental_model

Mutagenesis and structural mapping of the GIRK cytoplasmic domain

exposure

Alcohol binding to a defined hydrophobic pocket

limitations

Locates the site to a discrete pocket, which supports direct binding over a bulk membrane effect.

nutrient_topic

Alcohol research collection; topical membership is not evidence of a direct clinical effect, and ethanol is recorded separately from the acetaldehyde it becomes. · Ethanol

organism

Recombinant channels

plain_language

The same picture again: a specific pocket, not a general softening of the membrane.

primary_references

[alcohol-p19561601] A discrete alcohol pocket involved in GIRK channel activation. (2009). https://pubmed.ncbi.nlm.nih.gov/19561601/ DOI: 10.1038/nn.2358

tissue_or_cell_type

GIRK cytoplasmic domain

Alcohol: ethanol clearance, acetaldehyde, the channels it binds, organ injury and nutrient collisions (2026-09-21) · lines 397–408

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Mutagenesis and structural mapping of the GIRK cytoplasmic domain · source_derived_draft · unverified_draft

### alcohol-girk-pocket A discrete alcohol pocket in the channel cytoplasmic domain was shown to be involved in GIRK channel activation. Condition category: normal nutrient_topic: Alcohol research collection; topical membership is not evidence of a direct clinical effect, and ethanol is recorded separately from the acetaldehyde it becomes. plain_language: The same picture again: a specific pocket, not a general softening of the membrane. organism: Recombinant channels tissue_or_cell_type: GIRK cytoplasmic domain experimental_model: Mutagenesis and structural mapping of the GIRK cytoplasmic domain limitations: Locates the site to a discrete pocket, which supports direct binding over a bulk membrane effect. exposure: Alcohol binding to a defined hydrophobic pocket evidence_span: {"source_cache": "artifacts/alcohol-research/19561601.abstract.txt", "locator": "Indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "6aa4c10bd615439d1b5e008da1031a4ed244aeef6a0be4764930a7f183778428", "start_char": 0, "end_char": 1103, "text_sha256": "6aa4c10bd615439d1b5e008da1031a4ed244aeef6a0be4764930a7f183778428"} [alcohol-p19561601] A discrete alcohol pocket involved in GIRK channel activation. (2009). https://pubmed.ncbi.nlm.nih.gov/19561601/ DOI: 10.1038/nn.2358

evidence_span

{"source_cache": "artifacts/alcohol-research/10570485.abstract.txt", "locator": "Indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "42da0b6588f0ec74c04be8d7a13a0aec3d34ed9e01b92af9cfad92eb3e79714b", "start_char": 0, "end_char": 827, "text_sha256": "42da0b6588f0ec74c04be8d7a13a0aec3d34ed9e01b92af9cfad92eb3e79714b"}

experimental_model

Heterologous expression of GIRK channels with alcohol application

exposure

Intoxicating alcohol concentrations

limitations

Establishes the channel family as a direct target. Recombinant expression, not native neurons.

nutrient_topic

Alcohol research collection; topical membership is not evidence of a direct clinical effect, and ethanol is recorded separately from the acetaldehyde it becomes. · Ethanol

organism

Recombinant channels

plain_language

Alcohol opens a potassium channel that quietens neurons.

primary_references

[alcohol-p10570485] G-protein-coupled inwardly rectifying potassium channels are targets of alcohol action. (1999). https://pubmed.ncbi.nlm.nih.gov/10570485/ DOI: 10.1038/16012

tissue_or_cell_type

Neuronal potassium channels

Alcohol: ethanol clearance, acetaldehyde, the channels it binds, organ injury and nutrient collisions (2026-09-21) · lines 384–395

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Heterologous expression of GIRK channels with alcohol application · source_derived_draft · unverified_draft

### alcohol-girk-target G-protein-gated inwardly rectifying potassium channels are targets of alcohol action, activated at intoxicating concentrations. Condition category: normal nutrient_topic: Alcohol research collection; topical membership is not evidence of a direct clinical effect, and ethanol is recorded separately from the acetaldehyde it becomes. plain_language: Alcohol opens a potassium channel that quietens neurons. organism: Recombinant channels tissue_or_cell_type: Neuronal potassium channels experimental_model: Heterologous expression of GIRK channels with alcohol application limitations: Establishes the channel family as a direct target. Recombinant expression, not native neurons. exposure: Intoxicating alcohol concentrations evidence_span: {"source_cache": "artifacts/alcohol-research/10570485.abstract.txt", "locator": "Indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "42da0b6588f0ec74c04be8d7a13a0aec3d34ed9e01b92af9cfad92eb3e79714b", "start_char": 0, "end_char": 827, "text_sha256": "42da0b6588f0ec74c04be8d7a13a0aec3d34ed9e01b92af9cfad92eb3e79714b"} [alcohol-p10570485] G-protein-coupled inwardly rectifying potassium channels are targets of alcohol action. (1999). https://pubmed.ncbi.nlm.nih.gov/10570485/ DOI: 10.1038/16012