ArticleProceedings of the National Academy of Sciences of the United States of America2008
Identification of a BK channel auxiliary protein controlling molecular and behavioral tolerance to alcohol.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2008. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 62 papers.
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Who cites it
62 citing papers in PubMed, 86 citations in OpenAlex.
- Pharmacological Relevance of β-, γ-, and LINGO Auxiliary Subunits in BK Channel Modulation.ChemMedChem · 2026Review
- Paraoxonase 3 regulates the pore-forming α subunit of the large-conductance KBiochimica et biophysica acta. Molecular cell research · 2025Article
- Hispidol Regulates Behavioral Responses to Ethanol through Modulation of BK Channels: A Novel Candidate for the Treatment of Alcohol Use Disorder.Molecules (Basel, Switzerland) · 2024Article
- Article
- Ethanol's interaction with BK channel α subunit residue K361 does not mediate behavioral responses to alcohol in mice.Molecular psychiatry · 2024Article
- Ethanol Metabolite, Acetate, Increases Excitability of the Central Nucleus of Amygdala Neurons through Activation of NMDA Receptors.ACS chemical neuroscience · 2023Article
- KCurrent neuropharmacology · 2023Review
- Alcohol Sensitivity as an Endophenotype of Alcohol Use Disorder: Exploring Its Translational Utility between Rodents and Humans.Brain sciences · 2020Review
- Molecular structures of the human Slo1 KeLife · 2019Article
- Ethanol Elevates Excitability of Superior Cervical Ganglion Neurons by Inhibiting Kv7 Channels in a Cell Type-Specific and PI(4,5)PInternational journal of molecular sciences · 2019Article
- A Novel Peptide Restricts Ethanol Modulation of the BK Channel In Vitro and In Vivo.The Journal of pharmacology and experimental therapeutics · 2018Article
- Review
- BK β1 subunit-dependent facilitation of ethanol inhibition of BK current and cerebral artery constriction is mediated by the β1 transmembrane domain 2.British journal of pharmacology · 2017Article
- Behavioral Deficits Following Withdrawal from Chronic Ethanol Are Influenced by SLO Channel Function inGenetics · 2017Article
- Titrating Tipsy Targets: The Neurobiology of Low-Dose Alcohol.Trends in pharmacological sciences · 2017Review
- Genomewide Association Study of Alcohol Dependence Identifies Risk Loci Altering Ethanol-Response Behaviors in Model Organisms.Alcoholism, clinical and experimental research · 2017Article
- Ethanol-Sensitive Pacemaker Neurons in the Mouse External Globus Pallidus.Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology · 2017Article
- Alcohol modulation of BK channel gating depends on β subunit composition.The Journal of general physiology · 2016Article
- Alcohol Regulates BK Surface Expression via Wnt/β-Catenin Signaling.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2016Article
- Modulation of BK Channels by Ethanol.International review of neurobiology · 2016Review
2 more citing papers are in PubMed but not listed here.
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Authors and funding
7 authors at 1 institution in 1 country.
Funding
Abstract
Tolerance, described as the loss of drug effectiveness over time, is an important component of addiction. The degree of acute behavioral tolerance to alcohol exhibited by a naïve subject can predict the likelihood of alcohol abuse. Thus, the determinants of acute tolerance are important to understand. Calcium- and voltage-gated (BK) potassium channels, consisting of pore forming alpha and modulatory beta subunits, are targets of ethanol (EtOH) action. Here, we examine the role, at the molecular, cellular, and behavioral levels, of the BK beta4 subunit in acute tolerance. Single channel recordings in HEK-293 cells show that, in the absence of beta4, EtOH potentiation of activity exhibits acute tolerance, which is blocked by coexpressing the beta4 subunit. BK channels in acutely isolated medium spiny neurons from WT mice (in which the beta4 subunit is well-represented) exhibit little tolerance. In contrast, neuronal BK channels from beta4 knockout (KO) mice do display acute tolerance. Brain slice recordings showed tolerance to EtOH's effects on spike patterning in KO but not in WT mice. In addition, beta4 KO mice develop rapid tolerance to EtOH's locomotor effects, whereas WT mice do not. Finally, in a restricted access ethanol self-administration assay, beta4 KO mice drink more than their WT counterparts. Taken together, these data indicate that the beta4 subunit controls ethanol tolerance at the molecular, cellular, and behavioral levels, and could determine individual differences in alcohol abuse and alcoholism, as well as represent a therapeutic target for alcoholism.
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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.