ArticleFrontiers in cellular neuroscience2011
Enhanced Synaptic Activity and Epileptiform Events in the Embryonic KCC2 Deficient Hippocampus.
Article in Frontiers in cellular neuroscience, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers.
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Who cites it
21 citing papers in PubMed, 40 citations in OpenAlex.
- Functional KCC2 expression marks an evolutionarily conserved population of early-maturing interneurons in the perinatal cortex.Nature communications · 2025Article
- Sex-specific differences in KCC2 localisation and inhibitory synaptic transmission in the rat hippocampus.Scientific reports · 2022Article
- The role of KCC2 in hyperexcitability of the neonatal brain.Neuroscience letters · 2020Article
- Regulation of Thyroid-disrupting Chemicals to Protect the Developing Brain.Endocrinology · 2020Review
- Loss of non-canonical KCC2 functions promotes developmental apoptosis of cortical projection neurons.EMBO reports · 2020Article
- KCC2-Mediated ClCell reports · 2019Article
- KCC2 Regulates Dendritic Spine Formation in a Brain-Region Specific and BDNF Dependent Manner.Cerebral cortex (New York, N.Y. : 1991) · 2018Article
- ASTN2 modulates synaptic strength by trafficking and degradation of surface proteins.Proceedings of the National Academy of Sciences of the United States of America · 2018Article
- Regulating the Efficacy of Inhibition Through Trafficking of γ-Aminobutyric Acid Type A Receptors.Anesthesia and analgesia · 2016Review
- Disruption of Kcc2-dependent inhibition of olfactory bulb output neurons suggests its importance in odour discrimination.Nature communications · 2016Article
- Kinase-KCC2 coupling: Cl- rheostasis, disease susceptibility, therapeutic target.Journal of neurophysiology · 2016Review
- Homeostatic regulation of KCC2 activity by the zinc receptor mZnR/GPR39 during seizures.Neurobiology of disease · 2015Article
- Expanding Spectrum of Sodium Potassium Chloride Co-transporters in the Pathophysiology of Diseases.Current neuropharmacology · 2015Review
- Cation-chloride cotransporters in neuronal development, plasticity and disease.Nature reviews. Neuroscience · 2014Review
- A variant of KCC2 from patients with febrile seizures impairs neuronal Cl- extrusion and dendritic spine formation.EMBO reports · 2014Article
- Current view on the functional regulation of the neuronal K(+)-Cl(-) cotransporter KCC2.Frontiers in cellular neuroscience · 2014Review
- Activity-dependent cleavage of the K-Cl cotransporter KCC2 mediated by calcium-activated protease calpain.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2012Article
- Raising cytosolic Cl- in cerebellar granule cells affects their excitability and vestibulo-ocular learning.The EMBO journal · 2012Article
- Refuting the challenges of the developmental shift of polarity of GABA actions: GABA more exciting than ever!Frontiers in cellular neuroscience · 2012Article
- The Yin and Yen of GABA in Brain Development and Operation in Health and Disease.Frontiers in cellular neuroscience · 2012Article
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Authors and funding
15 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The neuronal potassium-chloride co-transporter 2 [indicated thereafter as KCC2 (for protein) and Kcc2 (for gene)] is thought to play an important role in the post natal excitatory to inhibitory switch of GABA actions in the rodent hippocampus. Here, by studying hippocampi of wild-type (Kcc2(+/+)) and Kcc2 deficient (Kcc2(-/-)) mouse embryos, we unexpectedly found increased spontaneous neuronal network activity at E18.5, a developmental stage when KCC2 is thought not to be functional in the hippocampus. Embryonic Kcc2(-/-) hippocampi have also an augmented synapse density and a higher frequency of spontaneous glutamatergic and GABA-ergic postsynaptic currents than naïve age matched neurons. However, intracellular chloride concentration ([Cl(-)](i)) and the reversal potential of GABA-mediated currents (E(GABA)) were similar in embryonic Kcc2(+/+) and Kcc2(-/-) CA3 neurons. In addition, KCC2 immunolabeling was cytoplasmic in the majority of neurons suggesting that the molecule is not functional as a plasma membrane chloride co-transporter. Collectively, our results show that already at an embryonic stage, KCC2 controls the formation of synapses and, when deleted, the hippocampus has a higher density of GABA-ergic and glutamatergic synapses and generates spontaneous and evoked epileptiform activities. These results may be explained either by a small population of orchestrating neurons in which KCC2 operates early as a chloride exporter or by transporter independent actions of KCC2 that are instrumental in synapse formation and networks construction.
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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.