Component
The alpha-1 subunit histidine-101-to-arginine point mutation
The alpha-1 subunit histidine-101-to-arginine point mutation. Species, exposure and limitations are retained in each linked claim.
1 recorded relationships. Experimental role, claim status and evidence remain attached to each record.
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.
Other things that act on it
Enzymes, hormones, genes, and other components with a recorded effect. These are not nutrients, so they do not count toward the arrows above. Each finding names the chapter that recorded it.
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.
What it acts on
By introducing a histidine-to-arginine point mutation at position 101 of the murine alpha1-subunit gene, alpha1-type GABA-A receptors which are mainly expressed in cortical areas and thalamus are rendered insensitive to allosteric modulation by benzodiazepine-site ligands whilst regulation by the physiological neurotransmitter GABA is preserved, alpha1(H101R) mice failed to show the sedative, amnesic and partly the anticonvulsant action of diazepam, in contrast the anxiolytic-like, myorelaxant, motor-impairing and ethanol-potentiating effects were fully retained and are attributed to the nonmutated receptors found in the limbic system, in monoaminergic neurons and in motoneurons.
Experimental context and source evidence
- evidence_span
- {"source_cache": "artifacts/gaba-research/10548105.abstract.txt", "locator": "Indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "73f8793d4606905cc7330c56b3345629a48e652c824f1dfecc9c4670c3c9b74b", "start_char": 0, "end_char": 1270, "text_sha256": "73f8793d4606905cc7330c56b3345629a48e652c824f1dfecc9c4670c3c9b74b"}
- experimental_model
- Knock-in mice carrying a point mutation that removes benzodiazepine sensitivity from one subunit
- exposure
- A histidine-to-arginine point mutation at position 101 of the alpha-1 subunit, with diazepam
- limitations
- A single-residue knock-in that separates drug actions by subunit. GABA regulation of the mutated receptor is preserved, which is what makes the dissociation clean.
- 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
- Change one amino acid and the same drug stops sedating the animal while still calming it, because different effects run through different subunits.
- primary_references
- [gb-p10548105] Benzodiazepine actions mediated by specific gamma-aminobutyric acid(A) receptor subtypes. (1999). https://pubmed.ncbi.nlm.nih.gov/10548105/ DOI: 10.1038/44579
- tissue_or_cell_type
- Cortex, thalamus and limbic system
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Knock-in mice carrying a point mutation that removes benzodiazepine sensitivity from one subunit · source_derived_draft · unverified_draft
### gb-one-subunit-carries-the-sedation By introducing a histidine-to-arginine point mutation at position 101 of the murine alpha1-subunit gene, alpha1-type GABA-A receptors which are mainly expressed in cortical areas and thalamus are rendered insensitive to allosteric modulation by benzodiazepine-site ligands whilst regulation by the physiological neurotransmitter GABA is preserved, alpha1(H101R) mice failed to show the sedative, amnesic and partly the anticonvulsant action of diazepam, in contrast the anxiolytic-like, myorelaxant, motor-impairing and ethanol-potentiating effects were fully retained and are attributed to the nonmutated receptors found in the limbic system, in monoaminergic neurons and in motoneurons. 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: Change one amino acid and the same drug stops sedating the animal while still calming it, because different effects run through different subunits. organism: Mouse tissue_or_cell_type: Cortex, thalamus and limbic system experimental_model: Knock-in mice carrying a point mutation that removes benzodiazepine sensitivity from one subunit limitations: A single-residue knock-in that separates drug actions by subunit. GABA regulation of the mutated receptor is preserved, which is what makes the dissociation clean. exposure: A histidine-to-arginine point mutation at position 101 of the alpha-1 subunit, with diazepam evidence_span: {"source_cache": "artifacts/gaba-research/10548105.abstract.txt", "locator": "Indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "73f8793d4606905cc7330c56b3345629a48e652c824f1dfecc9c4670c3c9b74b", "start_char": 0, "end_char": 1270, "text_sha256": "73f8793d4606905cc7330c56b3345629a48e652c824f1dfecc9c4670c3c9b74b"} [gb-p10548105] Benzodiazepine actions mediated by specific gamma-aminobutyric acid(A) receptor subtypes. (1999). https://pubmed.ncbi.nlm.nih.gov/10548105/ DOI: 10.1038/44579
Complete structured claim and evidence
The events it takes part in
A mechanism often involves more than two components. These are the full events, with every participant and its role.
Situations it appears in
Low-supply and faulty-machinery situations recorded in the chapters where this component plays a part.
In the sources
Preserved passages that mention this component, quoted exactly. Open one to read it in context.
Open hypotheses
Proposed ideas that involve this component. They are labeled as hypotheses and do not change any recorded statement.
This is a research prototype built from draft material. It is not medical advice, and its statements still await verification against the original studies.