ArticleFrontiers in neuroscience2011
Bestrophin1 Channels are Insensitive to Ethanol and Do not Mediate Tonic GABAergic Currents in Cerebellar Granule Cells.
Article in Frontiers in neuroscience, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 23 papers.
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Who cites it
23 citing papers in PubMed, 30 citations in OpenAlex.
- Suppression of In Vitro Epileptiform Activity by GABA Transaminase Inhibition Is Dependent on GABAThe Journal of neuroscience : the official journal of the Society for Neuroscience · 2026Article
- The pentameric chloride channel BEST1 is activated by extracellular GABA.Proceedings of the National Academy of Sciences of the United States of America · 2025Article
- GABA, but Not Bestrophin-1, Is Localized in Astroglial Processes in the Mouse Hippocampus and the Cerebellum.Frontiers in molecular neuroscience · 2020Article
- Diverse Actions of Astrocytes in GABAergic Signaling.International journal of molecular sciences · 2019Review
- Control of motor coordination by astrocytic tonic GABA release through modulation of excitation/inhibition balance in cerebellum.Proceedings of the National Academy of Sciences of the United States of America · 2018Article
- The Cerebellar GABAHandbook of experimental pharmacology · 2018Article
- Physiology of Astroglia.Physiological reviews · 2018Review
- Modulation of Tonic GABA Currents by Anion Channel and Connexin Hemichannel Antagonists.Neurochemical research · 2017Article
- Distribution and Function of the Bestrophin-1 (Best1) Channel in the Brain.Experimental neurobiology · 2017Review
- Sensitivity of GABAergic Tonic Currents to Acute Ethanol in Cerebellar Granule Neurons is Not Age- or δ Subunit-Dependent in Developing Rats.Alcoholism, clinical and experimental research · 2016Article
- Ethanol-Induced Cerebellar Ataxia: Cellular and Molecular Mechanisms.Cerebellum (London, England) · 2015Article
- Enhanced astroglial GABA uptake attenuates tonic GABAA inhibition of the presympathetic hypothalamic paraventricular nucleus neurons in heart failure.Journal of neurophysiology · 2015Article
- Mini-Review: Effects of Ethanol on GABAA Receptor-Mediated Neurotransmission in the Cerebellar Cortex--Recent Advances.Cerebellum (London, England) · 2015Review
- Repeated intermittent alcohol exposure during the third trimester-equivalent increases expression of the GABA(A) receptor δ subunit in cerebellar granule neurons and delays motor development in rats.Neuropharmacology · 2014Article
- GABA as a rising gliotransmitter.Frontiers in neural circuits · 2014Review
- Integration and regulation of glomerular inhibition in the cerebellar granular layer circuit.Frontiers in cellular neuroscience · 2014Review
- Acute ethanol exposure inhibits silencing of cerebellar Golgi cell firing induced by granule cell axon input.Frontiers in integrative neuroscience · 2014Article
- Neurosteroid interactions with synaptic and extrasynaptic GABA(A) receptors: regulation of subunit plasticity, phasic and tonic inhibition, and neuronal network excitability.Psychopharmacology · 2013Review
- A functional role for both -aminobutyric acid (GABA) transporter-1 and GABA transporter-3 in the modulation of extracellular GABA and GABAergic tonic conductances in the rat hippocampus.The Journal of physiology · 2013Article
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Authors and funding
5 authors at 2 institutions in 1 country.
Funding
Abstract
The granule cell layer of the cerebellum functions in spatio-temporal encoding of information. Granule cells (GCs) are tonically inhibited by spillover of GABA released from Golgi cells and this tonic inhibition is facilitated by acute ethanol. Recently, it was demonstrated that a specialized Ca(2+)-activated anion-channel, bestrophin1 (Best1), found on glial cells, can release GABA that contributes up to 50-75% of the tonic GABAergic current. However, it is unknown if ethanol has any actions on Best1 function. Using whole-cell electrophysiology, we found that recombinant Best1 channels expressed in HEK-293 cells were insensitive to 40 and 80 mM ethanol. We attempted to measure the Best1-mediated component of the tonic current in slices using 5-nitro-2-(3-phenylpropylamino)benzoic acid (NPPB). We confirmed that this agent blocks recombinant Best1 channels. Unexpectedly, we found that NPPB significantly potentiated the tonic current and the area and decay of GABA(A)-mediated spontaneous inhibitory post-synaptic currents (IPSCs) in GCs in rodent slices under two different recording conditions. To better isolate the Best1-dependent tonic current component, we blocked the Golgi cell component of the tonic current with tetrodotoxin and found that NPPB similarly and significantly potentiated the tonic current amplitude and decay time of miniature IPSCs. Two other Cl(-)-channel blockers were also tested: 4'-diisothiocyanatostilbene-2,2'-disulfonic acid disodium salt hydrate (DIDS) showed no effect on GABAergic transmission, while niflumic acid (NFA) significantly suppressed the tonic current noise, as well as the mIPSC frequency, amplitude, and area. These data suggest that acute ethanol exposure does not modulate Best1 channels and these findings serve to challenge recent data indicating that these channels participate in the generation of tonic GABAergic currents in cerebellar GCs.
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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.