ArticleProceedings of the National Academy of Sciences of the United States of America2013
Molecular mechanism underlying ethanol activation of G-protein-gated inwardly rectifying potassium channels.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 49 papers.
What it found
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Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
49 citing papers in PubMed, 67 citations in OpenAlex.
- A randomized controlled study of the effect of ifenprodil on alcohol use in patients with alcohol dependence.Neuropsychopharmacology reports · 2018Trial
- Alcohol and Hypertension-A Fresh Look on the Mechanistic Aspects of a Fatal Epidemiologic Relationship.Biomolecules · 2026Review
- Naltrexone and Nalmefene as Modern Psychopharmacotherapy for Alcohol Use Disorder: Modulation of Opioid Receptors and Neurobiological Pathways of Alcohol Action.Biomedicines · 2026Review
- Heavy adolescent drinking makes the adult brain more vulnerable to ethanol by permanently altering the age-dependent interplay between alcohol, GIRK channels and activin.Molecular psychiatry · 2026Article
- A critical residue mediates proper assembly and gating of GIRK2 channels.The Journal of general physiology · 2026Article
- G protein-gated inwardly rectifying KHistology and histopathology · 2025Review
- Invasion of glioma cells through confined space requires membrane tension regulation and mechano-electrical coupling via Plexin-B2.Nature communications · 2025Article
- Synaptic Effects Induced by Alcohol.Current topics in behavioral neurosciences · 2025Review
- Chronic ethanol exposure in mice evokes pre- and postsynaptic deficits in GABAergic transmission in ventral tegmental area GABA neurons.British journal of pharmacology · 2025Article
- A neurodevelopmental disorder mutation locks G proteins in the transitory pre-activated state.Nature communications · 2024Article
- Direct modulation of G protein-gated inwardly rectifying potassium (GIRK) channels.Frontiers in physiology · 2024Review
- Dual regulation of Kv7.2/7.3 channels by long-chain n-alcohols.The Journal of general physiology · 2023Article
- Alcohol reverses the effects of KCNJ6 (GIRK2) noncoding variants on excitability of human glutamatergic neurons.Molecular psychiatry · 2023Article
- Evaluation of Candidates for Systemic Analgesia and General Anesthesia in the Emerging Model Cephalopod,Biology · 2023Article
- The Relevance of GIRK Channels in Heart Function.Membranes · 2022Review
- Neuronal G protein-gated KAmerican journal of physiology. Cell physiology · 2022Review
- A novel small-molecule selective activator of homomeric GIRK4 channels.The Journal of biological chemistry · 2022Article
- Article
- Alcohol Use Disorder: Neurobiology and Therapeutics.Biomedicines · 2022Review
- Aminophylline at clinically relevant concentrations affects inward rectifier potassium current in a dual way.Pflugers Archiv : European journal of physiology · 2022Article
Corrections and comments
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Authors and funding
2 authors at 1 institution in 1 country.
Funding
Abstract
Alcohol (ethanol) produces a wide range of pharmacological effects on the nervous system through its actions on ion channels. The molecular mechanism underlying ethanol modulation of ion channels is poorly understood. Here we used a unique method of alcohol-tagging to demonstrate that alcohol activation of a G-protein-gated inwardly rectifying potassium (GIRK or Kir3) channel is mediated by a defined alcohol pocket through changes in affinity for the membrane phospholipid signaling molecule phosphatidylinositol 4,5-bisphosphate. Surprisingly, hydrophobicity and size, but not the canonical hydroxyl, were important determinants of alcohol-dependent activation. Altering levels of G protein Gβγ subunits, conversely, did not affect alcohol-dependent activation, suggesting a fundamental distinction between receptor and alcohol gating of GIRK channels. The chemical properties of the alcohol pocket revealed here might extend to other alcohol-sensitive proteins, revealing a unique protein microdomain for targeting alcohol-selective therapeutics in the treatment of alcoholism and addiction.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.