ArticleProceedings of the National Academy of Sciences of the United States of America2006
Anomalous levels of Cl- transporters in the hippocampal subiculum from temporal lobe epilepsy patients make GABA excitatory.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2006. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 147 papers.
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Who cites it
147 citing papers in PubMed, 304 citations in OpenAlex.
- A Preliminary Study Evaluating the Safety and Efficacy of Bumetanide, an NKCC1 Inhibitor, in Patients with Drug-Resistant Epilepsy.CNS drugs · 2019Trial
- WNK-SPAK/OSR1 signaling pathway facilitates ictal activity via reduced neuronal chloride extrusion rate.bioRxiv : the preprint server for biology · 2026Article
- Abnormal KCC2 expression and function in a mouse model of epilepsy and tuberous sclerosis complex.Epilepsia · 2026Article
- GABACellular and molecular neurobiology · 2026Review
- Plasma KCC2, NKCC1, and GABA as peripheral biomarkers in autism spectrum disorder: a combined ROC analysis.Metabolic brain disease · 2026Article
- Presynaptic chloride-dependent regulation of spontaneous glutamate release in the rat medial preoptic nucleus.Frontiers in cellular neuroscience · 2026Article
- Article
- Bezafibrate treatment rescues neurodevelopmental and neurodegenerative defects in 3D cortical organoid model of MAPT frontotemporal dementia.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2025Article
- An Evaluation of Cation-Chloride Cotransporters NKCC1 and KCC2 in Carbamazepine-Resistant Rats.International journal of molecular sciences · 2025Article
- The Bidirectional Relationship Between Epilepsy and Alzheimer's Disease.Current neurology and neuroscience reports · 2025Review
- Circuit Reorganization of Subicular Cell-Type-Specific Interneurons in Temporal Lobe Epilepsy.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2025Article
- Article
- Excitatory-inhibitory imbalance in temporal lobe epilepsy: a 5T multimodal MRI biomarker for focus localization and drug resistance stratification.Frontiers in aging neuroscience · 2025Article
- Specific and Plastic: Chandelier Cell-to-Axon Initial Segment Connections in Shaping Functional Cortical Network.Neuroscience bulletin · 2024Review
- Excitatory neurons and oligodendrocyte precursor cells are vulnerable to focal cortical dysplasia type IIIa as suggested by single-nucleus multiomics.Clinical and translational medicine · 2024Article
- Multiple layers of diversity govern the cell type specificity of GABAergic input received by mouse subicular pyramidal neurons.The Journal of physiology · 2024Article
- Seizures exacerbate excitatory: inhibitory imbalance in Alzheimer's disease and 5XFAD mice.Brain : a journal of neurology · 2024Article
- Impaired GABAergic regulation and developmental immaturity in interneurons derived from the medial ganglionic eminence in the tuberous sclerosis complex.Acta neuropathologica · 2024Article
- Membranes and Synaptosomes Used to Investigate Synaptic GABAergic Currents in Epileptic Patients.Membranes · 2024Article
- Development of KCC2 therapeutics to treat neurological disorders.Frontiers in molecular neuroscience · 2024Article
87 more citing papers are in PubMed but not listed here.
Corrections and comments
- Commented on by
- Erratum issued
Authors and funding
11 authors at 3 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The mRNA levels of NKCC1, an inwardly directed Na(+), K(+)-2Cl(-) cotransporter that facilitates the accumulation of intracellular Cl(-), and of KCC2, an outwardly directed K(+)-Cl(-) cotransporter that extrudes Cl(-), were studied in surgically resected brain specimens from drug-resistant temporal lobe (TL) epilepsy (TLE) patients. Quantitative RT-PCR analyses of the mRNAs extracted from the human TLE-associated brain regions revealed an up-regulation of NKCC1 mRNA and a down-regulation of KCC2 mRNA in the hippocampal subiculum, compared with the hippocampus proper or the TL neocortex, suggesting an abnormal transcription of Cl(-) transporters in the TLE subiculum. In parallel experiments, cell membranes isolated from the same TLE-associated brain regions were injected into Xenopus oocytes that rapidly incorporated human GABA(A) receptors into their surface membrane. The GABA currents elicited in oocytes injected with membranes from the subiculum had a more depolarized reversal potential (E(GABA)) compared with the hippocampus proper or the neocortex. The NKCC1 blocker bumetanide or a temperature decrease of 10 degrees C shifted the GABA-current E(GABA) more negative in oocytes injected with membranes from TLE hippocampal subiculum, matching the E(GABA) of TL neocortex-injected oocytes. We conclude that the anomalous expression of both Cl(-) transporters, NKCC1 and KCC2 [corrected] in TLE hippocampal subiculum probably causes altered Cl(-) transport in the "epileptic" neurons, as revealed in the microtransplanted Xenopus oocytes, and renders GABA aberrantly "exciting," a feature that may contribute to the precipitation of epileptic seizures.
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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.