ArticleMolecular pharmacology2008
Ethanol modulates BKCa channels by acting as an adjuvant of calcium.
Article in Molecular pharmacology, 2008. 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, 55 citations in OpenAlex.
- Molecular determinants of cholesterol binding to BK channel-forming slo1 subunits.Archives of biochemistry and biophysics · 2026Article
- Potential therapeutic targeting of BKMolecular oncology · 2026Review
- Ethanol alters mechanosensory habituation in C. elegans by way of the BK potassium channel through a novel mechanism.PloS one · 2025Article
- Ethanol's interaction with BK channel α subunit residue K361 does not mediate behavioral responses to alcohol in mice.Molecular psychiatry · 2024Article
- Aging in nucleus accumbens and its impact on alcohol use disorders.Alcohol (Fayetteville, N.Y.) · 2023Review
- Alcohol and pregnenolone interaction on cerebral arteries through targeting of vascular smooth muscleAdvances in drug and alcohol research · 2023Article
- Cholesterol and PIPAdvances in experimental medicine and biology · 2023Article
- Cholesterol Inhibition of Slo1 Channels Is Calcium-Dependent and Can Be Mediated by Either High-Affinity Calcium-Sensing Site in the Slo1 Cytosolic Tail.Molecular pharmacology · 2022Article
- BK channel clustering is required for normal behavioral alcohol sensitivity in C. elegans.Scientific reports · 2019Article
- Cross-species molecular dissection across alcohol behavioral domains.Alcohol (Fayetteville, N.Y.) · 2018Review
- 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
- Genomewide Association Study of Alcohol Dependence Identifies Risk Loci Altering Ethanol-Response Behaviors in Model Organisms.Alcoholism, clinical and experimental research · 2017Article
- Low-Dose Ethanol Preconditioning Protects Against Oxygen-Glucose Deprivation/Reoxygenation-Induced Neuronal Injury By Activating Large Conductance, CaNeuroscience bulletin · 2017Article
- Distinct mechanisms underlying cholesterol protection against alcohol-induced BK channel inhibition and resulting vasoconstriction.Biochimica et biophysica acta · 2016Article
- Alcohol modulation of BK channel gating depends on β subunit composition.The Journal of general physiology · 2016Article
- Functional Interactions between BKOxidative medicine and cellular longevity · 2016Article
- Modulation of BK Channels by Ethanol.International review of neurobiology · 2016Review
- Ethanol Effect on BK Channels is Modulated by Magnesium.Alcoholism, clinical and experimental research · 2015Article
- Putative calcium-binding domains of the Caenorhabditis elegans BK channel are dispensable for intoxication and ethanol activation.Genes, brain, and behavior · 2015Article
- Simulation of alcohol action upon a detailed Purkinje neuron model and a simpler surrogate model that runs >400 times faster.BMC neuroscience · 2015Article
Corrections and comments
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Authors and funding
5 authors at 3 institutions in 1 country.
Funding
Abstract
Ethanol modulation of calcium- and voltage-gated potassium (slo1) channels alters neuronal excitability, cerebrovascular tone, brain function, and behavior, yet the mechanism of this modulation remains unknown. Using patch-clamp electrophysiology on recombinant BK(Ca) channels cloned from mouse brain and expressed in Xenopus laevis oocytes, we demonstrate that ethanol, even at concentrations maximally effective to modulate BK(Ca) channel function (100 mM), fails to gate the channel in absence of activating calcium. Moreover, ethanol does not modify intrinsic, voltage- or physiological magnesium-driven gating. The alcohol works as an adjuvant of calcium by selectively facilitating calcium-driven gating. This facilitation, however, renders differential ethanol effects on channel activity: potentiation at low (<10 microM) and inhibition at high (>10 microM) calcium, this dual pattern remaining largely unmodified by coexpression of brain slo1 channels with the neuronally abundant BK(Ca) channel beta(4) subunit. Calcium recognition by either of the slo1 high-affinity sensors (calcium bowl and RCK1 Asp362/Asp367) is required for ethanol to amplify channel activation by calcium. The Asp362/Asp367 site, however, is necessary and sufficient to sustain ethanol inhibition. This inhibition also results from ethanol facilitation of calcium action; in this case, ethanol favors channel dwelling in a calcium-driven, low-activity mode. The agonist-adjuvant mechanism that we advance from the calcium-ethanol interaction on slo1 might be applicable to data of ethanol action on a wide variety of ligand-gated channels.
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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.