ArticleThe Journal of physiology2010
The K+-Cl cotransporter KCC2 promotes GABAergic excitation in the mature rat hippocampus.
Article in The Journal of physiology, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 114 papers, 1 of them a synthesis that pooled it.
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Who cites it
114 citing papers in PubMed, 1 synthesis or guideline pooled it, 202 citations in OpenAlex.
- GABAFrontiers in neural circuits · 2022Pooled it
- WNK-SPAK/OSR1 signaling pathway facilitates ictal activity via reduced neuronal chloride extrusion rate.bioRxiv : the preprint server for biology · 2026Article
- Neuron-derived neurotrophic factor-positive interneurons: a cellular target for anti-seizure therapies.EBioMedicine · 2026Article
- NKCC1: A key regulator of glioblastoma progression.Molecular oncology · 2026Article
- 4-Aminopyridine induced hyperpolarizing oscillations in pediatric human epileptic tissue are network-driven potassium currents that are abolished by activation of KCNQ2-5 (Kv7.2-Kv7.5) channels.Neurobiology of disease · 2026Article
- Applications of Carbonic Anhydrase Inhibitors in Neurological Disorders, Mechanisms and Therapeutic Potential.Sub-cellular biochemistry · 2026Review
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- WONOEP XVII appraisal: Targeting network excitability beyond the synapse -Neurotransmitter, ionic, and electro -diffusions.Epilepsia · 2025Review
- Hippocampal Interneurons Shape Spatial Coding Alterations in Neurological Disorders.Molecular neurobiology · 2025Review
- Interneuron-Driven Ictogenesis in the 4-Aminopyridine Model: Depolarization Block and Potassium Accumulation Initiate Seizure-like Activity.International journal of molecular sciences · 2025Article
- Modulation ofCurrent neuropharmacology · 2025Article
- Rate-Dependent Depression of the Hoffmann Reflex: Practical Applications in Painful Diabetic Neuropathy.Diabetes & metabolism journal · 2024Review
- Brainstem depolarization-induced lethal apnea associated with gain-of-functionProceedings of the National Academy of Sciences of the United States of America · 2024Article
- Extracellular glutamate and GABA transients at the transition from interictal spiking to seizures.Brain : a journal of neurology · 2024Article
- Review
- Ion Channels and Ionotropic Receptors in Astrocytes: Physiological Functions and Alterations in Alzheimer's Disease and Glioblastoma.Life (Basel, Switzerland) · 2023Review
- Optogenetic stimulation reveals a latent tipping point in cortical networks during ictogenesis.Brain : a journal of neurology · 2023Article
- Indirect Effects of Halorhodopsin Activation: Potassium Redistribution, Nonspecific Inhibition, and Spreading Depolarization.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2023Article
- High and Low-Frequency Stimulation Effect on Epileptiform Activity in Brain Slices.Medical journal of the Islamic Republic of Iran · 2023Article
54 more citing papers are in PubMed but not listed here.
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Authors and funding
4 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
GABAergic excitatory [K(+)](o) transients can be readily evoked in the mature rat hippocampus by intense activation of GABA(A) receptors (GABA(A)Rs). Here we show that these [K(+)](o) responses induced by high-frequency stimulation or GABA(A) agonist application are generated by the neuronal K(+)-Cl() cotransporter KCC2 and that the transporter-mediated KCl extrusion is critically dependent on the bicarbonate-driven accumulation of Cl() in pyramidal neurons. The mechanism underlying GABAergic [K(+)](o) transients was studied in CA1 stratum pyramidale using intracellular sharp microelectrodes and extracellular ion-sensitive microelectrodes. The evoked [K(+)](o) transients, as well as the associated afterdischarges, were strongly suppressed by 0.5-1 mm furosemide, a KCl cotransport inhibitor. Importantly, the GABA(A)R-mediated intrapyramidal accumulation of Cl(), as measured by monitoring the reversal potential of fused IPSPs, was unaffected by the drug. It was further confirmed that the reduction in the [K(+)](o) transients was not due to effects of furosemide on the Na(+)-dependent K(+)-Cl() cotransporter NKCC1 or on intraneuronal carbonic anhydrase activity. Blocking potassium channels by Ba(2+) enhanced [K(+)](o) transients whereas pyramidal cell depolarizations were attenuated in further agreement with a lack of contribution by channel-mediated K(+) efflux. The key role of the GABA(A)R channel-mediated anion fluxes in the generation of the [K(+)](o) transients was examined in experiments where bicarbonate was replaced with formate. This anion substitution had no significant effect on the rate of Cl() accumulation, [K(+)](o) response or afterdischarges. Our findings reveal a novel excitatory mode of action of KCC2 that can have substantial implications for the role of GABAergic transmission during ictal epileptiform activity.
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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.