ArticleGlia2009
Pharmacological "cross-inhibition" of connexin hemichannels and swelling activated anion channels.
Article in Glia, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 65 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
65 citing papers in PubMed, 111 citations in OpenAlex.
- Mechanism of action of two potent LRRC8/VRAC channel inhibitors.Research square · 2026Article
- Contractions of ex-vivo mouse bladder driven by activation of channelrhodopsin-2 expressed in urothelial cells.Scientific reports · 2025Article
- The SWELL1 Channel Promotes Ischemic Brain Damage by Mediating Neuronal Swelling and Glutamate Toxicity.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2024Article
- Article
- Astroglial connexin 43 is a novel therapeutic target for chronic multiple sclerosis model.Scientific reports · 2024Article
- VRAC channel inhibition as a novel strategy for the treatment of ischemia-reperfusion injury.Frontiers in cell and developmental biology · 2024Review
- ATP-releasing SWELL1 channel in spinal microglia contributes to neuropathic pain.Science advances · 2023Article
- Somatic GJA4 gain-of-function mutation in orbital cavernous venous malformations.Angiogenesis · 2023Article
- Structure-based discovery and in vitro validation of inhibitors of chloride intracellular channel 4 protein.Computational and structural biotechnology journal · 2023Article
- NF-κB and AP-1 are required for the lipopolysaccharide-induced expression of MCP-1, CXCL1, and Cx43 in cultured rat dorsal spinal cord astrocytes.Frontiers in molecular neuroscience · 2022Article
- Chloride transport modulators as drug candidates.American journal of physiology. Cell physiology · 2021Review
- Expression and Functionality of Connexin-Based Channels in Human Liver Cancer Cell Lines.International journal of molecular sciences · 2021Article
- NMDARs, Coincidence Detectors of Astrocytic and Neuronal Activities.International journal of molecular sciences · 2021Review
- Compromised Astrocyte Swelling/Volume Regulation in the Hippocampus of the Triple Transgenic Mouse Model of Alzheimer's Disease.Frontiers in aging neuroscience · 2021Article
- Analysing Intercellular Communication in Astrocytic Networks Using "Astral".Frontiers in cellular neuroscience · 2021Article
- The LRRC8 volume-regulated anion channel inhibitor, DCPIB, inhibits mitochondrial respiration independently of the channel.Physiological reports · 2019Article
- Structural determinants underlying permeant discrimination of the Cx43 hemichannel.The Journal of biological chemistry · 2019Article
- Metabolic constraints of swelling-activated glutamate release in astrocytes and their implication for ischemic tissue damage.Journal of neurochemistry · 2019Article
- CysLT1 receptor antagonists pranlukast and zafirlukast inhibit LRRC8-mediated volume regulated anion channels independently of the receptor.American journal of physiology. Cell physiology · 2019Article
- Chloride Channels in Astrocytes: Structure, Roles in Brain Homeostasis and Implications in Disease.International journal of molecular sciences · 2019Review
5 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
4 authors at 3 institutions in 2 countries.
Funding
Abstract
The study of ion channels has relied heavily on the use of pharmacological blocking agents. However, many of these agents have multiple effects, which may compromise interpretation of results when the affected mechanisms/pathways mediate similar functions. Volume regulated anion channels (VRAC) and connexin hemichannels can both mediate the release of glutamate and taurine, although these channels have distinct activation stimuli and hemichannels, but not VRAC, are permeable to Lucifer Yellow (LY). It has been reported that some anion channel blockers may inhibit connexin hemichannels. We further examined the effects of classic gap junction/hemichannel blockers and anion channel blockers on these channels. The typical VRAC blockers, NPPB, IAA-94, and tamoxifen blocked low divalent cation-induced glutamate and taurine release and LY loading, presumed due to hemichannel opening. The blocking action of these compounds on hemichannels was concentration dependent and fell within the same range where the drugs classically block VRACs. Conversely, carbenoxolone (CBX), the most widely used gap junction/hemichannel blocker, was an effective blocker of VRAC-mediated glutamate and taurine release, and blocked these channels at similar concentrations at which it blocked hemichannels. The CBX effect on VRACs was verified using astrocytes from connexin 43 knock out (Cx43 KO) animals. In these cells, the hypotonic induced amino acid flux was retained whereas the low divalent cation solution-induced flux was lost. These results extend our knowledge about "cross-inhibition" of VRACs and gap junctions/hemichannels by certain pharmacological agents. Given the overlap in function of these two types of channels, great care must be exerted in using pharmacological blockers to identify one channel from the other.
Indexed as
Identifiers
What 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.