ArticleThe Journal of neuroscience : the official journal of the Society for Neuroscience2012
Activity-dependent cleavage of the K-Cl cotransporter KCC2 mediated by calcium-activated protease calpain.
Article in The Journal of neuroscience : the official journal of the Society for Neuroscience, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 88 papers.
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Who cites it
88 citing papers in PubMed, 167 citations in OpenAlex.
- Regulated degradation of KCC2, a potassium-chloride co-transporter required for synaptic transmission and neurodevelopment.Channels (Austin, Tex.) · 2026Review
- WNK-SPAK/OSR1 signaling pathway facilitates ictal activity via reduced neuronal chloride extrusion rate.bioRxiv : the preprint server for biology · 2026Article
- Differential isoform-specific control of KCC2 function in developing and mature cortical neurons.EMBO reports · 2026Article
- Potential Role of Mitochondria-Associated Endoplasmic Reticulum Membranes (MAMs) Abnormalities in Epileptogenesis: Multimodal Mechanisms and Therapeutic Targets.Molecular neurobiology · 2026Review
- KCC2 phosphorylation dynamics relate to oligomerization during development and after spinal cord injury.Frontiers in molecular neuroscience · 2026Article
- Exploring the Cell Biological and Functional Effects of the First Disease Associated KCC1 Genetic Variant.Journal of cellular physiology · 2025Article
- Review
- Etomidate-Induced myoclonus in Sprague‒Dawley rats involves the activation of neocortical Calpain-2 and its decrement on KCC2 protein.BMC anesthesiology · 2025Article
- Article
- Knockdown of calpain1 in lumbar motoneurons reduces spasticity after spinal cord injury in adult rats.Molecular therapy : the journal of the American Society of Gene Therapy · 2024Article
- The expression system influences stability, maturation efficiency, and oligomeric properties of the potassium-chloride co-transporter KCC2.Neurochemistry international · 2024Article
- Uncovering novel KCC2 regulatory motifs through a comprehensive transposon-based mutant library.Frontiers in molecular neuroscience · 2024Article
- Development of KCC2 therapeutics to treat neurological disorders.Frontiers in molecular neuroscience · 2024Article
- NKCC1 and KCC2 Chloride Transporters Have Different Membrane Dynamics on the Surface of Hippocampal Neurons.Cells · 2023Article
- Emergence of consciousness from anesthesia through ubiquitin degradation of KCC2 in the ventral posteromedial nucleus of the thalamus.Nature neuroscience · 2023Article
- Article
- The amygdala lesioning due to status epilepticus - Changes in mechanisms controlling chloride homeostasis.Clinics (Sao Paulo, Brazil) · 2023Article
- Article
- Molecular Mechanisms of Epilepsy: The Role of the Chloride Transporter KCC2.Journal of molecular neuroscience : MN · 2022Review
- Furosemide prevents membrane KCC2 downregulation during convulsant stimulation in the hippocampus.IBRO neuroscience reports · 2022Article
28 more citing papers are in PubMed but not listed here.
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Authors and funding
4 authors at 1 institution in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The K-Cl cotransporter KCC2 plays a crucial role in neuronal chloride regulation. In mature central neurons, KCC2 is responsible for the low intracellular Cl(-) concentration ([Cl(-)](i)) that forms the basis for hyperpolarizing GABA(A) receptor-mediated responses. Fast changes in KCC2 function and expression have been observed under various physiological and pathophysiological conditions. Here, we show that the application of protein synthesis inhibitors cycloheximide and emetine to acute rat hippocampal slices have no effect on total KCC2 protein level and K-Cl cotransporter function. Furthermore, blocking constitutive lysosomal degradation with leupeptin did not induce significant changes in KCC2 protein levels. These findings indicate a low basal turnover rate of the total KCC2 protein pool. In the presence of the glutamate receptor agonist NMDA, the total KCC2 protein level decreased to about 30% within 4 h, and this effect was blocked by calpeptin and MDL-28170, inhibitors of the calcium-activated protease calpain. Interictal-like activity induced by incubation of hippocampal slices in an Mg(2+)-free solution led to a fast reduction in KCC2-mediated Cl(-) transport efficacy in CA1 pyramidal neurons, which was paralleled by a decrease in both total and plasmalemmal KCC2 protein. These effects were blocked by the calpain inhibitor MDL-28170. Taken together, these findings show that calpain activation leads to cleavage of KCC2, thereby modulating GABAergic signaling.
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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.