ArticleThe Journal of neuroscience : the official journal of the Society for Neuroscience2015
Selective inhibition of KCC2 leads to hyperexcitability and epileptiform discharges in hippocampal slices and in vivo.
Article in The Journal of neuroscience : the official journal of the Society for Neuroscience, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 60 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
60 citing papers in PubMed.
- WNK-SPAK/OSR1 signaling pathway facilitates ictal activity via reduced neuronal chloride extrusion rate.bioRxiv : the preprint server for biology · 2026Article
- Molecular pathways underlying amyloid precursor protein-mediated regulation of adult-born neurons.Neural regeneration research · 2026Article
- GABACellular and molecular neurobiology · 2026Review
- KCC2 activation during postnatal development alleviates long-term deficits in CDKL5-deficient mice.Experimental & molecular medicine · 2026Article
- Article
- Dynamic changes in chloride homeostasis coordinate midbrain inhibitory network activity during reward learning.Nature communications · 2025Article
- Sleep-wake-related changes in intracellular chloride regulate plasticity at glutamatergic cortical synapses.Current biology : CB · 2025Article
- KCC2 inhibition and neuronal hyperexcitability promote extrinsic apoptosis dependent upon C1q.Frontiers in molecular neuroscience · 2025Article
- Article
- Midbrain KCC2 downregulation: Implications for stress-related and substance use behaviors.Current opinion in neurobiology · 2024Review
- The brain-specific kinase LMTK3 regulates neuronal excitability by decreasing KCC2-dependent neuronal CliScience · 2024Article
- Constitutive KCC2 Cell- and Synapse-Specifically Regulates NMDA Receptor Activity in the Spinal Cord.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2024Article
- High Doses of ANA12 Improve Phenobarbital Efficacy in a Model of Neonatal Post-Ischemic Seizures.International journal of molecular sciences · 2024Article
- Neuronal KActa pharmacologica Sinica · 2024Review
- The role ofJournal of pharmaceutical analysis · 2023Review
- Angiotensin ATCell reports · 2023Article
- KCC2 reverse mode helps to clear postsynaptically released potassium at glutamatergic synapses.Cell reports · 2023Article
- Delaying the GABA Shift Indirectly Affects Membrane Properties in the Developing Hippocampus.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2023Article
- Article
- Molecular Mechanisms of Epilepsy: The Role of the Chloride Transporter KCC2.Journal of molecular neuroscience : MN · 2022Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
15 authors.
Funding
Abstract
GABA(A) receptors form Cl(-) permeable channels that mediate the majority of fast synaptic inhibition in the brain. The K(+)/Cl(-) cotransporter KCC2 is the main mechanism by which neurons establish low intracellular Cl(-) levels, which is thought to enable GABAergic inhibitory control of neuronal activity. However, the widely used KCC2 inhibitor furosemide is nonselective with antiseizure efficacy in slices and in vivo, leading to a conflicting scheme of how KCC2 influences GABAergic control of neuronal synchronization. Here we used the selective KCC2 inhibitor VU0463271 [N-cyclopropyl-N-(4-methyl-2-thiazolyl)-2-[(6-phenyl-3-pyridazinyl)thio]acetamide] to investigate the influence of KCC2 function. Application of VU0463271 caused a reversible depolarizing shift in E(GABA) values and increased spiking of cultured hippocampal neurons. Application of VU0463271 to mouse hippocampal slices under low-Mg(2+) conditions induced unremitting recurrent epileptiform discharges. Finally, microinfusion of VU0463271 alone directly into the mouse dorsal hippocampus rapidly caused epileptiform discharges. Our findings indicated that KCC2 function was a critical inhibitory factor ex vivo and in vivo.
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.