ArticleThe Journal of neuroscience : the official journal of the Society for Neuroscience2009
Mapping a barbiturate withdrawal locus to a 0.44 Mb interval and analysis of a novel null mutant identify a role for Kcnj9 (GIRK3) in withdrawal from pentobarbital, zolpidem, and ethanol.
Article in The Journal of neuroscience : the official journal of the Society for Neuroscience, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 42 papers.
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Who cites it
42 citing papers in PubMed, 58 citations in OpenAlex.
- A randomized controlled study of the effect of ifenprodil on alcohol use in patients with alcohol dependence.Neuropsychopharmacology reports · 2018Trial
- Atp1a2 and Kcnj9 Are Candidate Genes Underlying Sensitivity to Oxycodone-Induced Locomotor Activation and Withdrawal-Induced Anxiety-Like Behaviors in C57BL/6 Substrains.Genes, brain, and behavior · 2025Article
- Chronic ethanol exposure in mice evokes pre- and postsynaptic deficits in GABAergic transmission in ventral tegmental area GABA neurons.British journal of pharmacology · 2025Article
- Article
- A critical review of ethanol effects on neuronal firing: A metabolic perspective.Alcohol, clinical & experimental research · 2024Review
- Identification of common core ion channel genes in epilepsy and Alzheimer's disease.Irish journal of medical science · 2024Review
- Direct modulation of G protein-gated inwardly rectifying potassium (GIRK) channels.Frontiers in physiology · 2024Review
- Ethanol-Induced Suppression of G Protein-Gated Inwardly Rectifying KBiological psychiatry · 2023Article
- Review
- Neuronal G protein-gated KAmerican journal of physiology. Cell physiology · 2022Review
- G Protein-Gated Inwardly Rectifying Potassium Channel Subunit 3 is Upregulated in Rat DRGs and Spinal Cord After Peripheral Nerve Injury.Journal of pain research · 2020Article
- Genome-wide association study of alcohol use disorder identification test (AUDIT) scores in 20 328 research participants of European ancestry.Addiction biology · 2019Article
- Distinct Roles for Two Chromosome 1 Loci in Ethanol Withdrawal, Consumption, and Conditioned Place Preference.Frontiers in genetics · 2018Article
- Genetic studies of alcohol dependence in the context of the addiction cycle.Neuropharmacology · 2017Review
- G Protein-Gated Potassium Channels: A Link to Drug Addiction.Trends in pharmacological sciences · 2017Review
- Limbic circuitry activation in ethanol withdrawal is regulated by a chromosome 1 locus.Alcohol (Fayetteville, N.Y.) · 2017Article
- Differential potassium channel gene regulation in BXD mice reveals novel targets for pharmacogenetic therapies to reduce heavy alcohol drinking.Alcohol (Fayetteville, N.Y.) · 2017Article
- G Protein-Gated Inwardly Rectifying Potassium Channel Subunit 3 Knock-Out Mice Show Enhanced Ethanol Reward.Alcoholism, clinical and experimental research · 2016Article
- A Role for the GIRK3 Subunit in Methamphetamine-Induced Attenuation of GABAB Receptor-Activated GIRK Currents in VTA Dopamine Neurons.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2016Article
- A Systems Approach Implicates a Brain Mitochondrial Oxidative Homeostasis Co-expression Network in Genetic Vulnerability to Alcohol Withdrawal.Frontiers in genetics · 2016Article
Corrections and comments
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Authors and funding
5 authors at 2 institutions in 1 country.
Funding
Abstract
Here, we map a quantitative trait locus (QTL) with a large effect on predisposition to barbiturate (pentobarbital) withdrawal to a 0.44 Mb interval of mouse chromosome 1 syntenic with human 1q23.2. We report a detailed analysis of the genes within this interval and show that it contains 15 known and predicted genes, 12 of which demonstrate validated genotype-dependent transcript expression and/or nonsynonymous coding sequence variation that may underlie the influence of the QTL on withdrawal. These candidates are involved in diverse cellular functions including intracellular trafficking, potassium conductance and spatial buffering, and multimolecular complex dynamics, and indicate both established and novel aspects of neurobiological response to sedative-hypnotics. This work represents a substantial advancement toward identification of the gene(s) that underlie the phenotypic effects of the QTL. We identify Kcnj9 as a particularly promising candidate and report the development of a Kcnj9-null mutant model that exhibits significantly less severe withdrawal from pentobarbital as well as other sedative-hypnotics (zolpidem and ethanol) versus wild-type littermates. Reduced expression of Kcnj9, which encodes GIRK3 (Kir3.3), is associated with less severe sedative-hypnotic withdrawal. A multitude of QTLs for a variety of complex traits, including diverse responses to sedative-hypnotics, have been detected on distal chromosome 1 in mice, and as many as four QTLs on human chromosome 1q have been implicated in human studies of alcohol dependence. Thus, our results will be primary to additional efforts to identify genes involved in a wide variety of behavioral responses to sedative-hypnotics and may directly facilitate progress in human genetics.
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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.