ReviewFrontiers in cellular neuroscience2014
Current view on the functional regulation of the neuronal K(+)-Cl(-) cotransporter KCC2.
Review in Frontiers in cellular neuroscience, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 107 papers, 1 of them a synthesis that pooled it.
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Who cites it
107 citing papers in PubMed, 1 synthesis or guideline pooled it.
- Neural Stimulation and Molecular Mechanisms of Plasticity and Regeneration: A Review.Frontiers in cellular neuroscience · 2020Pooled it
- Abnormal KCC2 expression and function in a mouse model of epilepsy and tuberous sclerosis complex.Epilepsia · 2026Article
- KCC2 phosphorylation dynamics relate to oligomerization during development and after spinal cord injury.Frontiers in molecular neuroscience · 2026Article
- Synaptic-immune interactions in neuropathic pain: complement-mediated remodeling of spinal dorsal horn microcircuits.Frontiers in cell and developmental biology · 2026Review
- Exploring the Cell Biological and Functional Effects of the First Disease Associated KCC1 Genetic Variant.Journal of cellular physiology · 2025Article
- KCC2 enhancers normalize reflex responses and improve locomotor function after chronic spinal cord injury.The Journal of physiology · 2025Article
- Chloride Homeostasis in Neuronal Disorders: Bridging Measurement to Therapy.Life (Basel, Switzerland) · 2025Review
- Biophysical characterization and ion transport with cell-based and proteoliposome reconstitution assays of invertebrate KFEBS open bio · 2025Article
- Ectopic expression of the cation-chloride cotransporter KCC2 in blood exosomes as a biomarker for functional rehabilitation.Frontiers in molecular neuroscience · 2025Article
- Altered GABAergic signaling and chloride homeostasis in eye movement circuits during late neurodevelopment: implications for Alzheimer's disease therapy.Frontiers in pharmacology · 2025Review
- In vivo dynamic tracking of cerebral chloride regulation using molecularly tailored liquid/liquid interfacial ultramicro iontronics.Science advances · 2024Article
- Loss of the zinc receptor ZnR/GPR39 in mice enhances anxiety-related behavior and motor deficits, and modulates KCC2 expression in the amygdala.Behavioral and brain functions : BBF · 2024Article
- Article
- Regulation of Neuronal Chloride Homeostasis by Pro- and Mature Brain-Derived Neurotrophic Factor (BDNF) via KCC2 Cation-Chloride Cotransporters in Rat Cortical Neurons.International journal of molecular sciences · 2024Article
- The expression system influences stability, maturation efficiency, and oligomeric properties of the potassium-chloride co-transporter KCC2.Neurochemistry international · 2024Article
- Neuronal KActa pharmacologica Sinica · 2024Review
- Early establishment of chloride homeostasis in CRH neurons is altered by prenatal stress leading to fetal HPA axis dysregulation.Frontiers in molecular neuroscience · 2024Article
- Updating perspectives on spinal cord function: motor coordination, timing, relational processing, and memory below the brain.Frontiers in systems neuroscience · 2024Review
- Serine 937 phosphorylation enhances KCC2 activity and strengthens synaptic inhibition.Scientific reports · 2023Article
- The role ofJournal of pharmaceutical analysis · 2023Review
47 more citing papers are in PubMed but not listed here.
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Authors and funding
7 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
In the mammalian central nervous system (CNS), the inhibitory strength of chloride (Cl(-))-permeable GABAA and glycine receptors (GABAAR and GlyR) depends on the intracellular Cl(-) concentration ([Cl(-)]i). Lowering [Cl(-)]i enhances inhibition, whereas raising [Cl(-)]i facilitates neuronal activity. A neuron's basal level of [Cl(-)]i, as well as its Cl(-) extrusion capacity, is critically dependent on the activity of the electroneutral K(+)-Cl(-) cotransporter KCC2, a member of the SLC12 cation-Cl(-) cotransporter (CCC) family. KCC2 deficiency compromises neuronal migration, formation and the maturation of GABAergic and glutamatergic synaptic connections, and results in network hyperexcitability and seizure activity. Several neurological disorders including multiple epilepsy subtypes, neuropathic pain, and schizophrenia, as well as various insults such as trauma and ischemia, are associated with significant decreases in the Cl(-) extrusion capacity of KCC2 that result in increases of [Cl(-)]i and the subsequent hyperexcitability of neuronal networks. Accordingly, identifying the key upstream molecular mediators governing the functional regulation of KCC2, and modifying these signaling pathways with small molecules, might constitute a novel neurotherapeutic strategy for multiple diseases. Here, we discuss recent advances in the understanding of the mechanisms regulating KCC2 activity, and of the role these mechanisms play in neuronal Cl(-) homeostasis and GABAergic neurotransmission. As KCC2 mediates electroneutral transport, the experimental recording of its activity constitutes an important research challenge; we therefore also, provide an overview of the different methodological approaches utilized to monitor function of KCC2 in both physiological and pathological conditions.
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