ArticleThe Journal of neuroscience : the official journal of the Society for Neuroscience2003
Functional hemichannels in astrocytes: a novel mechanism of glutamate release.
Article in The Journal of neuroscience : the official journal of the Society for Neuroscience, 2003. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 320 papers.
What it found
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The trial behind it
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Who cites it
320 citing papers in PubMed.
- High levels of nitric oxide and peroxynitrite with protein nitration: a new therapeutic target for gliomas.Medical gas research · 2027Review
- Subunit-specific roles of LRRC8 proteins in determining glutamate permeability of astrocytic volume-regulated anion channels.American journal of physiology. Cell physiology · 2026Article
- When the gatekeeper falls: developmental vulnerability of the thalamic reticular nucleus in neonatal and pediatric hypoxic-ischemic brain injury.Frontiers in systems neuroscience · 2026Review
- Heterogeneity of astrocyte density, morphology and connexins in the mouse hippocampus.Frontiers in neuroanatomy · 2026Article
- Cannabinoid Ligand-Mediated Glycogen Depletion in Astrocytes Is Associated With Increased Intracellular Calcium, Energy Metabolism, and Membrane Dynamics.Journal of neurochemistry · 2025Article
- Connexin hemichannel blockade by abEC1.1 disrupts glioblastoma progression, suppresses invasiveness, and reduces hyperexcitability in preclinical models.Cell communication and signaling : CCS · 2025Article
- Neurotropic Murine β-Coronavirus Infection Causes Differential Expression of Connexin 47 in Oligodendrocyte Subpopulations Associated with Demyelination.Molecular neurobiology · 2025Article
- The Unexplored Role of Connexin Hemichannels in Promoting Facioscapulohumeral Muscular Dystrophy Progression.International journal of molecular sciences · 2025Review
- Progress of Astrocyte-Neuron Crosstalk in Central Nervous System Diseases.Neurochemical research · 2024Review
- The role of astrocytes in depression, its prevention, and treatment by targeting astroglial gliotransmitter release.Proceedings of the National Academy of Sciences of the United States of America · 2024Article
- Changes in Cx43 and AQP4 Proteins, and the Capture of 3 kDa Dextran in Subpial Astrocytes of the Rat Medial Prefrontal Cortex after Both Sham Surgery and Sciatic Nerve Injury.International journal of molecular sciences · 2024Article
- The SWELL1 Channel Promotes Ischemic Brain Damage by Mediating Neuronal Swelling and Glutamate Toxicity.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2024Article
- CaProceedings of the National Academy of Sciences of the United States of America · 2024Article
- Calcium Regulation of Connexin Hemichannels.International journal of molecular sciences · 2024Review
- Microglia in morphine tolerance: cellular and molecular mechanisms and therapeutic potential.Frontiers in pharmacology · 2024Review
- Repetitive pulsed-wave ultrasound stimulation suppresses neural activity by modulating ambient GABA levels via effects on astrocytes.Frontiers in cellular neuroscience · 2024Article
- Measuring Connexin Hemichannel Opening in Response to an InsP3-Mediated Cytosolic CaMethods in molecular biology (Clifton, N.J.) · 2024Article
- Vascular Endothelial Barrier Protection Prevents Atrial Fibrillation by Preserving Cardiac Nanostructure.JACC. Clinical electrophysiology · 2023Article
- The Key Role of Astrocytes in Amyotrophic Lateral Sclerosis and Their Commitment to Glutamate Excitotoxicity.International journal of molecular sciences · 2023Review
- Connexins in Cancer, the Possible Role of Connexin46 as a Cancer Stem Cell-Determining Protein.Biomolecules · 2023Review
260 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
4 authors.
Funding
Abstract
Little is known about the expression and possible functions of unopposed gap junction hemichannels in the brain. Emerging evidence suggests that gap junction hemichannels can act as stand-alone functional channels in astrocytes. With immunocytochemistry, dye uptake, and HPLC measurements, we show that astrocytes in vitro express functional hemichannels that can mediate robust efflux of glutamate and aspartate. Functional hemichannels were confirmed by passage of extracellular lucifer yellow (LY) into astrocytes in nominal divalent cation-free solution (DCFS) and the ability to block this passage with gap junction blocking agents. Glutamate/aspartate release (or LY loading) in DCFS was blocked by multivalent cations (Ca2+, Ba2+, Sr2+, Mg2+, and La3+) and by gap junction blocking agents (carbenoxolone, octanol, heptanol, flufenamic acid, and 18alpha-glycyrrhetinic acid) with affinities close to those reported for blockade of gap junction intercellular communication. Glutamate efflux via hemichannels was also accompanied by greatly reduced glutamate uptake. Glutamate release in DCFS, however, was not significantly mediated by reversal of the glutamate transporter: release did not saturate and was not blocked by glutamate transporter blockers. Control experiments in DCFS precluded glutamate release by volume-sensitive anion channels, P2X7 purinergic receptor pores, or general purinergic receptor activation. Blocking intracellular Ca2+ mobilization by BAPTA-AM or thapsigargin did not inhibit glutamate release in DCFS. Divalent cation removal also induced glutamate release from intact CNS white matter (acutely isolated optic nerve) that was blocked by carbenoxolone, suggesting the existence of functional hemichannels in situ. Our results indicated that astrocyte hemichannels could influence CNS levels of extracellular glutamate with implications for normal and pathological brain function.
Indexed as
Identifiers
12736329PMC6742182What OpenQuestion holds
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.