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CIP1 is an activator of the K+–Cl− cotransporter KCC2
Biochemical and Biophysical Research Communications, 2009In most neurons, efficient setting of the intracellular Cl(-)-concentration requires the coordinated regulation of the Cl(-)-inward transporter NKCC1 and the Cl(-)-outward transporter KCC2. Previously, the cation-chloride cotransporter interacting protein 1 (CIP1) was shown to inactivate NKCC1. Here, we investigated its role for KCC2 activity. After co-
Anna-Maria Hartmann +3 more
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VCP controls KCC2 degradation through FAF1 recruitment and accelerates emergence from anesthesia.
Proceedings of the National Academy of Sciences of the United States of AmericaUbiquitin-proteasomal degradation of K+/Cl- cotransporter 2 (KCC2) in the ventral posteromedial nucleus (VPM) has been demonstrated to serve as a common mechanism by which the brain emerges from anesthesia and regains consciousness. Ubiquitin-proteasomal
Peng Chen +4 more
semanticscholar +1 more source
The KCC2 Cotransporter and Human Epilepsy
The Neuroscientist, 2016The cation-Cl− cotransporter KCC2, encoded by SLC12A5, is required for the emergence and maintenance of GABAergic fast synaptic inhibition in organisms across evolution. These findings have suggested that KCC2 deficiency might play a role in the pathogenesis human epilepsy, but this has only recently been substantiated by two lines of genetic evidence.
Arjun Khanna +5 more
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Implication of KCC2 in the sensitization to morphine by chronic ethanol treatment in mice
Synapse, 2013Chronic consumption of ethanol has been reported to modify several molecular events in the central nervous system (CNS). Ethanol directly or indirectly stimulates mesolimbic dopaminergic neurons and increases the release of dopamine in the nucleus accumbens (NAc; Xiao et al., 2007).
Tomohisa Tsuyuki +8 more
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Benzyl prolinate derivatives as novel selective KCC2 blockers
Bioorganic & Medicinal Chemistry Letters, 2010The discovery and optimization of a novel class of selective submicromolar KCC2 blockers is described. Details of synthesis and SAR are given together with ADME properties of selected compounds. A methylsulfone residue on the R(1) phenyl group improved the overall general profile of these prolinate derivatives.
Cecile Pegurier +12 more
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Seizing Control of KCC2: A New Therapeutic Target for Epilepsy
Trends in Neurosciences, 2017Deficits in GABAergic inhibition result in the abnormal neuronal activation and synchronization that underlies seizures. However, the molecular mechanisms responsible for transforming a normal brain into an epileptic one remain largely unknown. Hyperpolarizing inhibition mediated by type A GABA (GABAA) receptors is dependent on chloride extrusion by ...
Stephen J. Moss +6 more
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Genetic and environmental regulators of Kcc2/KCC2 gene expression
2020Michele Yeo, Wolfgang Liedtke
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