ArticleThe Journal of neuroscience : the official journal of the Society for Neuroscience2009
Bestrophin-1 encodes for the Ca2+-activated anion channel in hippocampal astrocytes.
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 67 papers.
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Who cites it
67 citing papers in PubMed, 109 citations in OpenAlex.
- Astrocytes mediate the dopaminergic modulation of tonic GABAergic signaling in substantia nigra.Science advances · 2026Article
- Glial Ion Channels in Myelin Pathophysiology: Insights from Leukodystrophies.Life (Basel, Switzerland) · 2025Review
- A functional perspective on astrocyte heterogeneity.Trends in neurosciences · 2025Review
- Astrocytic BEST1 can serve as a target for functional recovery after ischemic stroke.Molecular therapy : the journal of the American Society of Gene Therapy · 2025Article
- Cryo-EM structures of mouse bestrophin 1 channel in closed and partially open conformations.Molecules and cells · 2025Article
- The pentameric chloride channel BEST1 is activated by extracellular GABA.Proceedings of the National Academy of Sciences of the United States of America · 2025Article
- A quantitative analysis of bestrophin 1 cellular localization in mouse cerebral cortex.Acta physiologica (Oxford, England) · 2025Article
- GAD65 tunes the functions of Best1 as a GABA receptor and a neurotransmitter conducting channel.Nature communications · 2024Article
- Generation of Astrocyte-specific BEST1 Conditional Knockout Mouse with Reduced Tonic GABA Inhibition in the Brain.Experimental neurobiology · 2024Article
- Astrocytes phenomics as new druggable targets in healthy aging and Alzheimer's disease progression.Frontiers in cellular neuroscience · 2024Review
- Repetitive pulsed-wave ultrasound stimulation suppresses neural activity by modulating ambient GABA levels via effects on astrocytes.Frontiers in cellular neuroscience · 2024Article
- Glutamate-releasing BEST1 channel is a new target for neuroprotection against ischemic stroke with wide time window.Acta pharmaceutica Sinica. B · 2023Article
- Synapse Dysfunctions in Multiple Sclerosis.International journal of molecular sciences · 2023Review
- Pharmacological modulation of chloride channels as a therapeutic strategy for neurological disorders.Frontiers in physiology · 2023Review
- GABA Release from Astrocytes in Health and Disease.International journal of molecular sciences · 2022Review
- Differential Proximity of Perisynaptic Astrocytic Best1 at the Excitatory and Inhibitory Tripartite Synapses in APP/PS1 and MAOB-KO Mice Revealed by Lattice Structured Illumination Microscopy.Experimental neurobiology · 2021Article
- Astrocytes respond to a neurotoxic Aβ fragment with state-dependent CaActa neuropathologica communications · 2021Article
- Glial Chloride Channels in the Function of the Nervous System Across Species.Advances in experimental medicine and biology · 2021Article
- Evaluating BEST1 mutations in pluripotent stem cell-derived retinal pigment epithelial cells.Methods in enzymology · 2021Article
- Macular dystrophies: clinical and imaging features, molecular genetics and therapeutic options.The British journal of ophthalmology · 2020Review
7 more citing papers are in PubMed but not listed here.
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Authors and funding
8 authors at 5 institutions in 3 countries.
Funding
Abstract
In mammalian brain, neurons and astrocytes are reported to express various chloride and anion channels, but the evidence for functional expression of Ca(2+)-activated anion channel (CAAC) and its molecular identity have been lacking. Here we report electrophysiological evidence for the CAAC expression and its molecular identity by mouse Bestrophin 1 (mBest1) in astrocytes of the mouse brain. Using Ca(2+) imaging and perforated-patch-clamp analysis, we demonstrate that astrocytes displayed an inward current at holding potential of -70 mV that was dependent on an increase in intracellular Ca(2+) after G(alphaq)-coupled receptor activation. This current was mediated mostly by anions and was sensitive to well known anion channel blockers such as niflumic acid, 5-nitro-2(3-phenylpropylamino)-benzoic acid, and flufenamic acid. To find the molecular identity of the anion channel responsible for the CAAC current, we analyzed the expression of candidate genes and found that the mRNA for mouse mBest1 is predominantly expressed in acutely dissociated or cultured astrocytes. Whole-cell patch-clamp analysis using HEK293T cells heterologously expressing full-length mBest1 showed a Ca(2+)-dependent current mediated by mBest1, with a complete impairment of the current by a putative pore mutation, W93C. Furthermore, mBest1-mediated CAAC from cultured astrocytes was significantly reduced by expression of mBest1-specific short hairpin RNA (shRNA), suggesting that the CAAC is mediated by a channel encoded by mBest1. Finally, hippocampal CA1 astrocytes in hippocampal slice also showed mBest1-mediated CAAC because it was inhibited by mBest1-specific shRNA. Collectively, these data provide molecular evidence that the mBest1 channel is responsible for CAAC function in astrocytes.
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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.