Gene Symbol: KCC2
Description: solute carrier family 12, member 5
Alias: KCC2, mKIAA1176, solute carrier family 12 member 5, K-Cl cotransporter 2, KCC2a variant 1, KCC2a-S25 variant 1, KCC2b variant 2, electroneutral potassium-chloride cotransporter 2, mKCC2, neuronal K-Cl cotransporter
Species: mouse
Products:     KCC2

Top Publications

  1. Bortone D, Polleux F. KCC2 expression promotes the termination of cortical interneuron migration in a voltage-sensitive calcium-dependent manner. Neuron. 2009;62:53-71 pubmed publisher
    ..Once in the cortex, upregulation of the potassium-chloride cotransporter KCC2 is both necessary and sufficient to reduce interneuron motility through its ability to reduce membrane potential ..
  2. Boulenguez P, Liabeuf S, Bos R, Bras H, Jean Xavier C, Brocard C, et al. Down-regulation of the potassium-chloride cotransporter KCC2 contributes to spasticity after spinal cord injury. Nat Med. 2010;16:302-7 pubmed publisher
    ..of low intracellular chloride (Cl-) concentration, which is maintained by the potassium-chloride cotransporter KCC2 (encoded by Slc12a5)...
  3. Rivera C, Voipio J, Thomas Crusells J, Li H, Emri Z, Sipilä S, et al. Mechanism of activity-dependent downregulation of the neuron-specific K-Cl cotransporter KCC2. J Neurosci. 2004;24:4683-91 pubmed
    ..fast-hyperpolarizing inhibition depends on extrusion of chloride by the neuron-specific K-Cl cotransporter, KCC2. Here we show that sustained interictal-like activity in hippocampal slices downregulates KCC2 mRNA and protein ..
  4. Li H, Khirug S, Cai C, Ludwig A, Blaesse P, Kolikova J, et al. KCC2 interacts with the dendritic cytoskeleton to promote spine development. Neuron. 2007;56:1019-33 pubmed
    The neuron-specific K-Cl cotransporter, KCC2, induces a developmental shift to render GABAergic transmission from depolarizing to hyperpolarizing...
  5. Blaesse P, Airaksinen M, Rivera C, Kaila K. Cation-chloride cotransporters and neuronal function. Neuron. 2009;61:820-38 pubmed publisher
    ..The rapidly expanding work on CCCs promotes our understanding of fundamental mechanisms that control brain development and functions under normal and pathophysiological conditions. ..
  6. Aguado F, Carmona M, Pozas E, Aguiló A, Martinez Guijarro F, Alcantara S, et al. BDNF regulates spontaneous correlated activity at early developmental stages by increasing synaptogenesis and expression of the K+/Cl- co-transporter KCC2. Development. 2003;130:1267-80 pubmed
    ..of GABA and glutamate ionotropic receptors, it does raise the expression of the recently cloned K(+)/Cl(-) KCC2 co-transporter, which is responsible for the conversion of GABA responses from depolarizing to inhibitory, through ..
  7. Ludwig A, Uvarov P, Soni S, Thomas Crusells J, Airaksinen M, Rivera C. Early growth response 4 mediates BDNF induction of potassium chloride cotransporter 2 transcription. J Neurosci. 2011;31:644-9 pubmed publisher
    ..of potassium chloride cotransporter 2b (KCC2b), the main isoform of the neuron-specific K-Cl cotransporter KCC2. We have previously shown that transcription factor early growth response 4 (Egr4) can activate the KCC2b promoter...
  8. Stein V, Hermans Borgmeyer I, Jentsch T, Hübner C. Expression of the KCl cotransporter KCC2 parallels neuronal maturation and the emergence of low intracellular chloride. J Comp Neurol. 2004;468:57-64 pubmed
    ..This switch is correlated with upregulation of KCC2, the neuronal isoform of the potassium-chloride cotransporter family...
  9. Bos R, Sadlaoud K, Boulenguez P, Buttigieg D, Liabeuf S, Brocard C, et al. Activation of 5-HT2A receptors upregulates the function of the neuronal K-Cl cotransporter KCC2. Proc Natl Acad Sci U S A. 2013;110:348-53 pubmed publisher
    ..low intracellular chloride concentration ([Cl(-)](i)), which is maintained by the potassium-chloride cotransporter KCC2. A reduction of KCC2 expression or function is implicated in the pathogenesis of several neurological disorders, ..

More Information


  1. Ludwig A, Li H, Saarma M, Kaila K, Rivera C. Developmental up-regulation of KCC2 in the absence of GABAergic and glutamatergic transmission. Eur J Neurosci. 2003;18:3199-206 pubmed
    ..in the concentration of intracellular chloride set by the expression of the neuron-specific K+-Cl- co-transporter, KCC2. A recent in vitro study [Ganguly et al...
  2. Rinehart J, Maksimova Y, Tanis J, Stone K, Hodson C, Zhang J, et al. Sites of regulated phosphorylation that control K-Cl cotransporter activity. Cell. 2009;138:525-36 pubmed publisher
    ..Homologous sites are phosphorylated in all human KCCs. KCC2 is partially phosphorylated in neonatal mouse brain and dephosphorylated in parallel with KCC2 activation...
  3. Uvarov P, Ludwig A, Markkanen M, Rivera C, Airaksinen M. Upregulation of the neuron-specific K+/Cl- cotransporter expression by transcription factor early growth response 4. J Neurosci. 2006;26:13463-73 pubmed
    The expression of the neuron-specific K+/Cl- cotransporter (KCC2) is restricted to the CNS and is strongly upregulated during neuronal maturation, yielding a low intracellular chloride concentration that is required for fast synaptic ..
  4. Balakrishnan V, Becker M, Löhrke S, Nothwang H, Güresir E, Friauf E. Expression and function of chloride transporters during development of inhibitory neurotransmission in the auditory brainstem. J Neurosci. 2003;23:4134-45 pubmed
    ..Here, we investigated the temporal expression of the K-Cl cotransporter KCC2 and the Na-K-Cl cotransporter NKCC1 in the lateral superior olive (LSO) of rats and mice...
  5. Lee H, Jurd R, Moss S. Tyrosine phosphorylation regulates the membrane trafficking of the potassium chloride co-transporter KCC2. Mol Cell Neurosci. 2010;45:173-9 pubmed publisher
    The activity of the neuronal-specific potassium chloride co-transporter KCC2 allows neurons to maintain low intracellular Cl(-) concentrations...
  6. Khirug S, Huttu K, Ludwig A, Smirnov S, Voipio J, Rivera C, et al. Distinct properties of functional KCC2 expression in immature mouse hippocampal neurons in culture and in acute slices. Eur J Neurosci. 2005;21:899-904 pubmed
    ..concentration of chloride caused by the functional expression of the neuron-specific K-Cl cotransporter KCC2. Whether a mere increase in the amount of KCC2 protein is the rate-limiting step in vivo, or a further activation ..
  7. Horn Z, Ringstedt T, Blaesse P, Kaila K, Herlenius E. Premature expression of KCC2 in embryonic mice perturbs neural development by an ion transport-independent mechanism. Eur J Neurosci. 2010;31:2142-55 pubmed publisher
    During neuronal maturation, the neuron-specific K-Cl co-transporter KCC2 lowers the intracellular chloride and thereby renders GABAergic transmission hyperpolarizing...
  8. Hübner C, Stein V, Hermans Borgmeyer I, Meyer T, Ballanyi K, Jentsch T. Disruption of KCC2 reveals an essential role of K-Cl cotransport already in early synaptic inhibition. Neuron. 2001;30:515-24 pubmed
    ..cotransporters can lower the intracellular chloride concentration [Cl(-)](i), including the neuronal isoform KCC2. We show that KCC2 knockout mice died immediately after birth due to severe motor deficits that also abolished ..
  9. Zhu L, Polley N, Mathews G, Delpire E. NKCC1 and KCC2 prevent hyperexcitability in the mouse hippocampus. Epilepsy Res. 2008;79:201-12 pubmed publisher
    ..We also show that expression of the outward K-Cl cotransporter, KCC2, prevents the development of hyperexcitability, as a reduction of KCC2 expression by half results in increased ..
  10. Shibasaki M, Masukawa D, Ishii K, Yamagishi Y, Mori T, Suzuki T. Involvement of the K+-Cl- co-transporter KCC2 in the sensitization to morphine-induced hyperlocomotion under chronic treatment with zolpidem in the mesolimbic system. J Neurochem. 2013;125:747-55 pubmed publisher
    ..This study investigated the involvement of K(+) -Cl(-) co-transporter 2 (KCC2) in the sensitization to morphine-induced hyperlocomotion after chronic treatment with zolpidem [a selective ..
  11. Uvarov P, Ludwig A, Markkanen M, Soni S, Hübner C, Rivera C, et al. Coexpression and heteromerization of two neuronal K-Cl cotransporter isoforms in neonatal brain. J Biol Chem. 2009;284:13696-704 pubmed publisher
    The neuron-specific K-Cl cotransporter KCC2 maintains the low intracellular chloride concentration required for the fast hyperpolarizing actions of inhibitory neurotransmitters...
  12. Vilen H, Eerikäinen S, Tornberg J, Airaksinen M, Savilahti H. Construction of gene-targeting vectors: a rapid Mu in vitro DNA transposition-based strategy generating null, potentially hypomorphic, and conditional alleles. Transgenic Res. 2001;10:69-80 pubmed
    ..utilizes a highly efficient in vitro transposition reaction of phage Mu, and tested it in a targeting of the mouse Kcc2 gene locus...
  13. Woo N, Lu J, England R, McClellan R, Dufour S, Mount D, et al. Hyperexcitability and epilepsy associated with disruption of the mouse neuronal-specific K-Cl cotransporter gene. Hippocampus. 2002;12:258-68 pubmed
    Four genes encode electroneutral, Na+-independent, K-Cl cotransporters. KCC2, is exclusively expressed in neurons where it is thought to drive intracellular Cl- to low concentrations and shift the reversal potential for Cl- conductances ..
  14. Stil A, Jean Xavier C, Liabeuf S, Brocard C, Delpire E, Vinay L, et al. Contribution of the potassium-chloride co-transporter KCC2 to the modulation of lumbar spinal networks in mice. Eur J Neurosci. 2011;33:1212-22 pubmed publisher
    ..The up-regulation of the outward-directed Cl(-) pump, the neuron-specific potassium-chloride co-transporter type 2 KCC2, has been shown to underlie this shift...
  15. Ikeda K, Onimaru H, Yamada J, Inoue K, Ueno S, Onaka T, et al. Malfunction of respiratory-related neuronal activity in Na+, K+-ATPase alpha2 subunit-deficient mice is attributable to abnormal Cl- homeostasis in brainstem neurons. J Neurosci. 2004;24:10693-701 pubmed
    ..The alpha2 subunit and a neuron-specific K-Cl cotransporter KCC2 were coimmunoprecipitated in a purified synaptic membrane fraction of wild-type fetuses...
  16. Pressey J, Mahadevan V, Khademullah C, Dargaei Z, Chevrier J, Ye W, et al. A kainate receptor subunit promotes the recycling of the neuron-specific K+-Cl- co-transporter KCC2 in hippocampal neurons. J Biol Chem. 2017;292:6190-6201 pubmed publisher
    ..transmembrane gradient of chloride, which is set by the neuron-specific K+-Cl- co-transporter KCC2. Reduced KCC2 levels in the neuronal membrane contribute to the generation of epilepsy, neuropathic pain, and ..
  17. Saadi R, He K, Hartnett K, Kandler K, Hershfinkel M, Aizenman E. SNARE-dependent upregulation of potassium chloride co-transporter 2 activity after metabotropic zinc receptor activation in rat cortical neurons in vitro. Neuroscience. 2012;210:38-46 pubmed publisher
    The major outward chloride transporter in neurons is the potassium chloride co-transporter 2 (KCC2), critical for maintaining an inhibitory reversal potential for GABA(A) receptor channels...
  18. Kosaka Y, Kin H, Tatetsu M, Uema I, Takayama C. Distinct development of GABA system in the ventral and dorsal horns in the embryonic mouse spinal cord. Brain Res. 2012;1486:39-52 pubmed publisher
  19. Denaxa M, Kalaitzidou M, Garefalaki A, Achimastou A, Lasrado R, Maes T, et al. Maturation-promoting activity of SATB1 in MGE-derived cortical interneurons. Cell Rep. 2012;2:1351-62 pubmed publisher
  20. Deidda G, Parrini M, Naskar S, Bozarth I, Contestabile A, Cancedda L. Reversing excitatory GABAAR signaling restores synaptic plasticity and memory in a mouse model of Down syndrome. Nat Med. 2015;21:318-26 pubmed publisher
    ..Our findings demonstrate that GABA is excitatory in adult DS mice and identify a new therapeutic approach for the potential rescue of cognitive disabilities in individuals with DS. ..
  21. Zhao B, Wong A, Murshid A, Bowie D, Presley J, Bedford F. Identification of a novel di-leucine motif mediating K(+)/Cl(-) cotransporter KCC2 constitutive endocytosis. Cell Signal. 2008;20:1769-79 pubmed publisher
    The neuron-specific potassium-chloride cotransporter 2 (KCC2) plays a crucial role, by controlling chloride extrusion, in the development and maintenance of inhibitory neurotransmission...
  22. Taylor Burds C, Cheng P, Wray S. Chloride Accumulators NKCC1 and AE2 in Mouse GnRH Neurons: Implications for GABAA Mediated Excitation. PLoS ONE. 2015;10:e0131076 pubmed publisher
    ..In contrast, KCC2 is the primary chloride extruder in neurons, expressed at high levels in the adult and contributes to ..
  23. Li X, Zhou J, Chen Z, Chen S, Zhu F, Zhou L. Long-term expressional changes of Na+ -K+ -Cl- co-transporter 1 (NKCC1) and K+ -Cl- co-transporter 2 (KCC2) in CA1 region of hippocampus following lithium-pilocarpine induced status epilepticus (PISE). Brain Res. 2008;1221:141-6 pubmed publisher
    NKCC1 and KCC2 are encoded by slc12 gene family and involved in the maintenance of intracellular chloride concentration which may be associated with epileptogenesis...
  24. Markkanen M, Karhunen T, Llano O, Ludwig A, Rivera C, Uvarov P, et al. Distribution of neuronal KCC2a and KCC2b isoforms in mouse CNS. J Comp Neurol. 2014;522:1897-914 pubmed publisher
    The neuronal K-Cl cotransporter KCC2 maintains the low intracellular chloride concentration required for the fast hyperpolarizing actions of inhibitory neurotransmitters in mature central nervous system (CNS)...
  25. Frederikse P, Kasinathan C. KCC2 expression supersedes NKCC1 in mature fiber cells in mouse and rabbit lenses. Mol Vis. 2015;21:1142-50 pubmed
    Na-K-Cl cotransporter 1 (NKCC1) and K-Cl cotransporter 2 (KCC2) have fundamental roles in neuron differentiation that are integrated with gamma-aminobutyric acid (GABA) and glutamate receptors, GABA synthesized by GAD25/65/67 encoded by ..
  26. Asiedu M, Mejia G, Ossipov M, Malan T, Kaila K, Price T. Modulation of spinal GABAergic analgesia by inhibition of chloride extrusion capacity in mice. J Pain. 2012;13:546-54 pubmed publisher
    ..Changes in K(+)-Cl(-) cotransporter isoform 2 (KCC2) expression or function that occur after peripheral nerve injury can result in an impairment in the Cl(-) extrusion ..
  27. Shulga A, Thomas Crusells J, Sigl T, Blaesse A, Mestres P, Meyer M, et al. Posttraumatic GABA(A)-mediated [Ca2+]i increase is essential for the induction of brain-derived neurotrophic factor-dependent survival of mature central neurons. J Neurosci. 2008;28:6996-7005 pubmed publisher
    ..corticospinal neurons in vivo that posttraumatic downregulation of the neuron-specific K-Cl cotransporter KCC2 leads to intracellular chloride accumulation by the Na-K-2Cl cotransporter NKCC1, resulting in GABA-induced [Ca2+](..
  28. Delpy A, Allain A, Meyrand P, Branchereau P. NKCC1 cotransporter inactivation underlies embryonic development of chloride-mediated inhibition in mouse spinal motoneuron. J Physiol. 2008;586:1059-75 pubmed
    ..action that turns to inhibition due to modification of the chloride equilibrium potential (E(Cl)) controlled by the KCC2 and NKCC1 transporters...
  29. Banke T, Gegelashvili G. Tonic activation of group I mGluRs modulates inhibitory synaptic strength by regulating KCC2 activity. J Physiol. 2008;586:4925-34 pubmed publisher
    The furosemide-sensitive potassium-chloride cotransporter (KCC2) plays an important role in establishing the intracellular chloride concentration in many neurons within the central nervous system...
  30. Takayama C, Inoue Y. Developmental localization of potassium chloride co-transporter 2 in granule cells of the early postnatal mouse cerebellum with special reference to the synapse formation. Neuroscience. 2006;143:757-67 pubmed
    ..chloride ion (Cl(-)) concentration ([Cl(-)](i)) which is regulated by the potassium (K(+))-Cl(-) co-transporter 2 (KCC2)...
  31. Jung G, Jeon J, Jung Y, Choi Y, Kim H, Kim J, et al. Clusterin/apolipoprotein J attenuates angiotensin II-induced renal fibrosis. PLoS ONE. 2014;9:e105635 pubmed publisher
    ..This study raises the possibility that clusterin could be used as a therapeutic target for Ang II-induced renal diseases. ..
  32. Tornberg J, Voikar V, Savilahti H, Rauvala H, Airaksinen M. Behavioural phenotypes of hypomorphic KCC2-deficient mice. Eur J Neurosci. 2005;21:1327-37 pubmed
    ..A major effector of this task in adult animals is the potassium-chloride co-transporter KCC2 that is selectively and abundantly expressed postsynaptically in most CNS neurons...
  33. Yousuf M, Zubkow K, Tenorio G, Kerr B. The chloride co-transporters, NKCC1 and KCC2, in experimental autoimmune encephalomyelitis (EAE). Neuroscience. 2017;344:178-186 pubmed publisher
    ..Na+-K+-2Cl- co-transporter 1 (NKCC1) and K+-Cl- co-transporter 2 (KCC2) generally dictate the tone of GABA/glycine inhibition by regulating intracellular chloride concentrations...
  34. Sallinen R, Tornberg J, Putkiranta M, Horelli Kuitunen N, Airaksinen M, Wessman M. Chromosomal localization of SLC12A5/Slc12a5, the human and mouse genes for the neuron-specific K(+)-Cl(-) cotransporter (KCC2) defines a new region of conserved homology. Cytogenet Cell Genet. 2001;94:67-70 pubmed
    ..b>KCC2 (gene symbol SLC12A5) is expressed exclusively in neurons within the central nervous system and abnormalities in ..
  35. Wojcik S, Katsurabayashi S, Guillemin I, Friauf E, Rosenmund C, Brose N, et al. A shared vesicular carrier allows synaptic corelease of GABA and glycine. Neuron. 2006;50:575-87 pubmed
    ..and glycinergic synaptic transmission does not impair the development of inhibitory synapses or the expression of KCC2, the K+ -Cl- cotransporter known to be essential for the establishment of inhibitory neurotransmission...
  36. Kitayama T, Morita K, Sultana R, Kikushige N, Mgita K, Ueno S, et al. Phospholipase C-related but catalytically inactive protein modulates pain behavior in a neuropathic pain model in mice. Mol Pain. 2013;9:23 pubmed publisher
    ..pattern was similar between PRIP-1 KO and DKO spinal cord, while expression of K(+)-Cl(-)-cotransporter-2 (KCC2), which controls the balance of neuronal excitation and inhibition, was significantly upregulated in DKO mice...
  37. Leupen S, Tobet S, Crowley W, Kaila K. Heterogeneous expression of the potassium-chloride cotransporter KCC2 in gonadotropin-releasing hormone neurons of the adult mouse. Endocrinology. 2003;144:3031-6 pubmed
    In mature central neurons, chloride extrusion mediated by the K-Cl cotransporter KCC2 appears to be largely responsible for the Cl(-) driving force that allows gamma-aminobutyric acid(A) (GABA(A)) receptor activation to trigger a ..
  38. Uvarov P, Pruunsild P, Timmusk T, Airaksinen M. Neuronal K+/Cl- co-transporter (KCC2) transgenes lacking neurone restrictive silencer element recapitulate CNS neurone-specific expression and developmental up-regulation of endogenous KCC2 gene. J Neurochem. 2005;95:1144-55 pubmed
    The K+/Cl- co-transporter KCC2 maintains the low intracellular chloride concentration required for fast synaptic inhibition and is exclusively expressed in neurones of the CNS...
  39. Clopath C, Badura A, De Zeeuw C, Brunel N. A cerebellar learning model of vestibulo-ocular reflex adaptation in wild-type and mutant mice. J Neurosci. 2014;34:7203-15 pubmed publisher
    ..The detailed model reproduces both the behavioral and electrophysiological data of both the wild-type and mutant mice and allows for experimentally testable predictions. ..
  40. Furukawa M, Tsukahara T, Tomita K, Iwai H, Sonomura T, Miyawaki S, et al. Neonatal maternal separation delays the GABA excitatory-to-inhibitory functional switch by inhibiting KCC2 expression. Biochem Biophys Res Commun. 2017;493:1243-1249 pubmed publisher
    ..Histological quantification of K+-Cl- co-transporter (KCC2) and Ca2+ imaging were performed to examine the timing of the GABA switch during the MS period...
  41. Liu Z, Neff R, Berg D. Sequential interplay of nicotinic and GABAergic signaling guides neuronal development. Science. 2006;314:1610-3 pubmed
    ..Synergistic with nicotinic excitation, GABAergic inhibition constrains neuronal morphology and innervation. The results reveal a multitiered activity-dependent strategy controlling neuronal development. ..
  42. Leonzino M, Busnelli M, Antonucci F, Verderio C, Mazzanti M, Chini B. The Timing of the Excitatory-to-Inhibitory GABA Switch Is Regulated by the Oxytocin Receptor via KCC2. Cell Rep. 2016;15:96-103 pubmed publisher
    ..Oxtr is necessary for the correct timing of the GABA switch by upregulating activity of the chloride cotransporter KCC2, (2) Oxtr, in a very early and narrow time window, directly modulates the functional activity of KCC2 by promoting ..
  43. Uvarov P, Ludwig A, Markkanen M, Pruunsild P, Kaila K, Delpire E, et al. A novel N-terminal isoform of the neuron-specific K-Cl cotransporter KCC2. J Biol Chem. 2007;282:30570-6 pubmed
    The neuronal K-Cl cotransporter KCC2 maintains the low intracellular chloride concentration required for the hyperpolarizing actions of inhibitory neurotransmitters gamma-aminobutyric acid and glycine in the central nervous system...
  44. Haapa S, Suomalainen S, Eerikäinen S, Airaksinen M, Paulin L, Savilahti H. An efficient DNA sequencing strategy based on the bacteriophage mu in vitro DNA transposition reaction. Genome Res. 1999;9:308-15 pubmed
    ..overlapping minicontigs, the sequence of the entire 10,288-bp region of mouse genome including six exons of mouse Kcc2 gene was obtained...
  45. MacKenzie G, O Toole K, Moss S, Maguire J. Compromised GABAergic inhibition contributes to tumor-associated epilepsy. Epilepsy Res. 2016;126:185-96 pubmed publisher
    ..of glutamate have been shown to dephosphorylate and downregulate the potassium chloride cotransporter KCC2, we hypothesized that glioma-induced alterations in KCC2 in the peritumoral region may play a role in tumor-..
  46. Gödde K, Gschwend O, Puchkov D, Pfeffer C, Carleton A, Jentsch T. Disruption of Kcc2-dependent inhibition of olfactory bulb output neurons suggests its importance in odour discrimination. Nat Commun. 2016;7:12043 pubmed publisher
    ..tufted cells (M/T cells), the principal neurons of the OB, by disrupting their potassium-chloride cotransporter 2 (Kcc2). Roughly, 70% of mice died around 3 weeks, but surviving mice appeared normal...
  47. Zechel S, Nakagawa Y, Ibanez C. Thalamo-cortical axons regulate the radial dispersion of neocortical GABAergic interneurons. elife. 2016;5: pubmed publisher
    ..Expression of the KCC2 cotransporter was elevated in interneurons of denervated cortex, and KCC2 deletion restored normal interneuron ..
  48. Kakizawa K, Watanabe M, Mutoh H, Okawa Y, Yamashita M, Yanagawa Y, et al. A novel GABA-mediated corticotropin-releasing hormone secretory mechanism in the median eminence. Sci Adv. 2016;2:e1501723 pubmed publisher
    ..The GABAA receptor (GABAAR) and the Na(+)-K(+)-2Cl(-) cotransporter (NKCC1), but not the K(+)-Cl(-) cotransporter (KCC2), were expressed in the terminals of the CRH neurons at the median eminence (ME)...
  49. Campbell S, Robel S, Cuddapah V, Robert S, Buckingham S, Kahle K, et al. GABAergic disinhibition and impaired KCC2 cotransporter activity underlie tumor-associated epilepsy. Glia. 2015;63:23-36 pubmed publisher
    ..In these neurons, the plasmalemmal expression of KCC2, which establishes the low [Cl(-) ]i required for GABAA R-mediated inhibition, is significantly decreased...
  50. Gackière F, Vinay L. Contribution of the potassium-chloride cotransporter KCC2 to the strength of inhibition in the neonatal rodent spinal cord in vitro. J Neurosci. 2015;35:5307-16 pubmed publisher
    In healthy mature motoneurons (MNs), KCC2 cotransporters maintain the intracellular chloride concentration at low levels, a prerequisite for postsynaptic inhibition mediated by GABA and glycine...
  51. Boettger T, Rust M, Maier H, Seidenbecher T, Schweizer M, Keating D, et al. Loss of K-Cl co-transporter KCC3 causes deafness, neurodegeneration and reduced seizure threshold. EMBO J. 2003;22:5422-34 pubmed
    ..These cells slowly degenerated, as did sensory hair cells. The present mouse model has revealed important cellular and systemic functions of KCC3 and is highly relevant for Anderman syndrome. ..
  52. Silayeva L, Deeb T, Hines R, Kelley M, Munoz M, Lee H, et al. KCC2 activity is critical in limiting the onset and severity of status epilepticus. Proc Natl Acad Sci U S A. 2015;112:3523-8 pubmed publisher
    The K(+)/Cl(-) cotransporter (KCC2) allows adult neurons to maintain low intracellular Cl(-) levels, which are a prerequisite for efficient synaptic inhibition upon activation of γ-aminobutyric acid receptors...
  53. Takayama C, Inoue Y. Developmental localization of potassium chloride co-transporter 2 (KCC2) in the Purkinje cells of embryonic mouse cerebellum. Neurosci Res. 2007;57:322-5 pubmed
    ..occurs as a result of decreasing the intracellular Cl(-) concentration regulated by K(+)-Cl(-) co-transporter 2 (KCC2)...
  54. Mahadevan V, Dargaei Z, Ivakine E, Hartmann A, Ng D, Chevrier J, et al. Neto2-null mice have impaired GABAergic inhibition and are susceptible to seizures. Front Cell Neurosci. 2015;9:368 pubmed publisher
    Neto2 is a transmembrane protein that interacts with the neuron-specific K(+)-Cl(-) cotransporter (KCC2) in the central nervous system (CNS)...
  55. Chapuis C, Autran S, Fortin G, Simmers J, Thoby Brisson M. Emergence of sigh rhythmogenesis in the embryonic mouse. J Physiol. 2014;592:2169-81 pubmed publisher
    ..either by pharmacological blockade, functional perturbation or natural maturation of the chloride co-transporters KCC2 or NKCC1 selectively, and in an age-dependent manner, altered the bi-phasic nature of sigh bursts and their ..
  56. Puskarjov M, Seja P, Heron S, Williams T, Ahmad F, Iona X, et al. A variant of KCC2 from patients with febrile seizures impairs neuronal Cl- extrusion and dendritic spine formation. EMBO Rep. 2014;15:723-9 pubmed publisher
    Genetic variation in SLC12A5 which encodes KCC2, the neuron-specific cation-chloride cotransporter that is essential for hyperpolarizing GABAergic signaling and formation of cortical dendritic spines, has not been reported in human ..
  57. Zhu L, Lovinger D, Delpire E. Cortical neurons lacking KCC2 expression show impaired regulation of intracellular chloride. J Neurophysiol. 2005;93:1557-68 pubmed
    ..In this study, we have used gene-targeted KCC2-/- mice to provide strong evidence that KCC2, the neuronal-specific K-Cl co-transporter, drives neuronal Cl- to low ..
  58. Khalilov I, Chazal G, Chudotvorova I, Pellegrino C, Corby S, Ferrand N, et al. Enhanced Synaptic Activity and Epileptiform Events in the Embryonic KCC2 Deficient Hippocampus. Front Cell Neurosci. 2011;5:23 pubmed publisher
    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 ..
  59. Roussa E, Speer J, Chudotvorova I, Khakipoor S, Smirnov S, Rivera C, et al. The membrane trafficking and functionality of the K+-Cl- co-transporter KCC2 is regulated by TGF-?2. J Cell Sci. 2016;129:3485-98 pubmed publisher
    Functional activation of the neuronal K(+)-Cl(-) co-transporter KCC2 (also known as SLC12A5) is a prerequisite for shifting GABAA responses from depolarizing to hyperpolarizing during development...
  60. Toda T, Ishida K, Kiyama H, Yamashita T, Lee S. Down-regulation of KCC2 expression and phosphorylation in motoneurons, and increases the number of in primary afferent projections to motoneurons in mice with post-stroke spasticity. PLoS ONE. 2014;9:e114328 pubmed publisher
    ..immunohistochemical and western blot analyses to examine the expression of the potassium-chloride cotransporter 2 (KCC2) and phosphorylation of the KCC2 serine residue, 940 (S940), since this is the main chloride extruder that affects ..
  61. Yeo M, Berglund K, Augustine G, Liedtke W. Novel repression of Kcc2 transcription by REST-RE-1 controls developmental switch in neuronal chloride. J Neurosci. 2009;29:14652-62 pubmed publisher
    Transcriptional upregulation of Kcc2b, the gene variant encoding the major isoform of the KCC2 chloride transporter, underlies a rapid perinatal decrease in intraneuronal chloride concentration (chloride shift), which is necessary for ..
  62. Hübner C, Hentschke M, Jacobs S, Hermans Borgmeyer I. Expression of the sodium-driven chloride bicarbonate exchanger NCBE during prenatal mouse development. Gene Expr Patterns. 2004;5:219-23 pubmed
    ..The ongoing expression of the KCl-co-transporter KCC2 eventually lowers [Cl(-)](i) in most CNS neurons and thus renders GABA hyperpolarizing...
  63. Acton B, Mahadevan V, Mercado A, Uvarov P, Ding Y, Pressey J, et al. Hyperpolarizing GABAergic transmission requires the KCC2 C-terminal ISO domain. J Neurosci. 2012;32:8746-51 pubmed publisher
    b>KCC2 is the neuron-specific member of the of K(+)-Cl(-) cotransporter gene family. It is also the only member of its family that is active under physiologically normal conditions, in the absence of osmotic stress...
  64. Friedel P, Kahle K, Zhang J, Hertz N, Pisella L, Buhler E, et al. WNK1-regulated inhibitory phosphorylation of the KCC2 cotransporter maintains the depolarizing action of GABA in immature neurons. Sci Signal. 2015;8:ra65 pubmed publisher
    ..switch" in the GABA function depends on a postnatal decrease in intraneuronal Cl(-) concentration mediated by KCC2, a Cl(-)-extruding K(+)-Cl(-) cotransporter...
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    The K-Cl cotransporter KCC2 plays a crucial role in the functional development of GABA(A)-mediated responses rendering GABA hyperpolarizing in adult neurons...
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    b>KCC2 is the neuron-specific K+-Cl(-) cotransporter required for maintaining low intracellular Cl(-), which is essential for fast inhibitory synaptic transmission in the mature CNS...
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    Cation chloride co-transporters, including K(+)-Cl(-) co-transporter 2 (KCC2) and Na(+)-K(+)-Cl(-) co-transporter 1 (NKCC1), are of particular importance to GABAergic transmission and thus involved in the development of hyperalgesia at ..
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    ..This GABA functional switch is mainly mediated by the up-regulation of KCC2, a potassium-chloride cotransporter that pumps Cl- outside neurons...
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    ..by a very low intracellular chloride concentration, generated by the neuronal potassium chloride co-transporter (KCC2) expressed in the postsynaptic neurons...
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    ..We now disrupted the Kcc2 K-Cl cotransporter specifically in either cell type to manipulate their excitability and inhibition by GABA(A)-..