Slc12a5

Summary

Gene Symbol: Slc12a5
Description: solute carrier family 12 member 5
Alias: Kcc2, solute carrier family 12 member 5, K-Cl cotransporter 2, electroneutral potassium-chloride cotransporter 2, furosemide-sensitive K-Cl cotransporter, neuronal K-Cl cotransporter, neuronal-specific K-Cl cotransporter, rKCC2, solute carrier family 12 (potassium-chloride transporter), member 5
Species: rat
Products:     Slc12a5

Top Publications

  1. Bartho P, Payne J, Freund T, Acsady L. Differential distribution of the KCl cotransporter KCC2 in thalamic relay and reticular nuclei. Eur J Neurosci. 2004;20:965-75 pubmed
    ..The distribution of KCl cotransporter type 2 (KCC2), the major neuronal chloride transporter that may underlie this effect, is unknown in the thalamus...
  2. Hasbargen T, Ahmed M, Miranpuri G, Li L, Kahle K, Resnick D, et al. Role of NKCC1 and KCC2 in the development of chronic neuropathic pain following spinal cord injury. Ann N Y Acad Sci. 2010;1198:168-72 pubmed publisher
    ..Na(+)-K(+)-Cl(-) cotransporter isoform 1 (NKCC1) and outwardly directed K(+)-Cl(-) cotransporter isoform 2 (KCC2). Inhibition of NKCC1 with its potent antagonist bumetanide reduces pain behavior in rats following SCI...
  3. Pellegrino C, Gubkina O, Schaefer M, Becq H, Ludwig A, Mukhtarov M, et al. Knocking down of the KCC2 in rat hippocampal neurons increases intracellular chloride concentration and compromises neuronal survival. J Physiol. 2011;589:2475-96 pubmed publisher
    b>KCC2 is a neuron-specific potassium-chloride co-transporter controlling intracellular chloride homeostasis in mature and developing neurons...
  4. Papp E, Rivera C, Kaila K, Freund T. Relationship between neuronal vulnerability and potassium-chloride cotransporter 2 immunoreactivity in hippocampus following transient forebrain ischemia. Neuroscience. 2008;154:677-89 pubmed publisher
    ..The neuron-specific K-Cl cotransporter 2 (KCC2) is necessary for maintaining the low intracellular chloride concentration required for the hyperpolarizing actions ..
  5. 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
    ..This study shows that the mammalian KCC2 gene (alias Slc12a5) generates two neuron-specific isoforms by using alternative promoters and first exons...
  6. Fiumelli H, Briner A, Puskarjov M, Blaesse P, Belem B, Dayer A, et al. An ion transport-independent role for the cation-chloride cotransporter KCC2 in dendritic spinogenesis in vivo. Cereb Cortex. 2013;23:378-88 pubmed publisher
    The neuron-specific K-Cl cotransporter, KCC2, is highly expressed in the vicinity of excitatory synapses in pyramidal neurons, and recent in vitro data suggest that this protein plays a role in the development of dendritic spines...
  7. Lee H, Deeb T, Walker J, Davies P, Moss S. NMDA receptor activity downregulates KCC2 resulting in depolarizing GABAA receptor-mediated currents. Nat Neurosci. 2011;14:736-43 pubmed publisher
    b>KCC2 is a neuron-specific K(+)-Cl(-) co-transporter that maintains a low intracellular Cl(-) concentration that is essential for hyperpolarizing inhibition mediated by GABA(A) receptors...
  8. Coull J, Boudreau D, Bachand K, Prescott S, Nault F, Sik A, et al. Trans-synaptic shift in anion gradient in spinal lamina I neurons as a mechanism of neuropathic pain. Nature. 2003;424:938-42 pubmed
    ..It involves a trans-synaptic reduction in the expression of the potassium-chloride exporter KCC2, and the consequent disruption of anion homeostasis in neurons of lamina I of the superficial dorsal horn, one of ..
  9. 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 ..

More Information

Publications74

  1. Jaenisch N, Witte O, Frahm C. Downregulation of potassium chloride cotransporter KCC2 after transient focal cerebral ischemia. Stroke. 2010;41:e151-9 pubmed publisher
    The potassium chloride cotransporter 2 (KCC2) is the main neuronal chloride extruder in the adult nervous system...
  2. Rivera C, Voipio J, Payne J, Ruusuvuori E, Lahtinen H, Lamsa K, et al. The K+/Cl- co-transporter KCC2 renders GABA hyperpolarizing during neuronal maturation. Nature. 1999;397:251-5 pubmed
    ..is coupled to a developmental induction of the expression of the neuronal (Cl-)-extruding K+/Cl- co-transporter, KCC2. Antisense oligonucleotide inhibition of KCC2 expression produces a marked positive shift in the reversal potential ..
  3. Cramer S, Baggott C, Cain J, Tilghman J, Allcock B, Miranpuri G, et al. The role of cation-dependent chloride transporters in neuropathic pain following spinal cord injury. Mol Pain. 2008;4:36 pubmed publisher
    ..of two major intracellular Cl- regulatory proteins, Na+-K+-Cl- cotransporter 1 (NKCC1) and K+-Cl- cotransporter 2 (KCC2), in neuropathic pain following spinal cord injury (SCI)...
  4. Payne J, Stevenson T, Donaldson L. Molecular characterization of a putative K-Cl cotransporter in rat brain. A neuronal-specific isoform. J Biol Chem. 1996;271:16245-52 pubmed
    ..polymerase chain reaction, and library screening, we have identified a putative K-Cl cotransporter isoform (KCC2) in rat brain that is specifically localized in neurons...
  5. Wang C, Shimizu Okabe C, Watanabe K, Okabe A, Matsuzaki H, Ogawa T, et al. Developmental changes in KCC1, KCC2, and NKCC1 mRNA expressions in the rat brain. Brain Res Dev Brain Res. 2002;139:59-66 pubmed
    We investigated the expressions of KCC1, KCC2 and NKCC1 mRNAs in the developing rat brain. The neuroepithelium showed abundant KCC1 and NKCC1 mRNA expressions, while KCC2 mRNA was not detected there...
  6. Toyoda H, Ohno K, Yamada J, Ikeda M, Okabe A, Sato K, et al. Induction of NMDA and GABAA receptor-mediated Ca2+ oscillations with KCC2 mRNA downregulation in injured facial motoneurons. J Neurophysiol. 2003;89:1353-62 pubmed
    ..A downregulation of K(+)-Cl(-) cotransporter (KCC2) mRNA, an increase in intracellular Cl(-) concentration ([Cl(-)](i)), and transformation of GABAergic ..
  7. Baldi R, Varga C, Tamas G. Differential distribution of KCC2 along the axo-somato-dendritic axis of hippocampal principal cells. Eur J Neurosci. 2010;32:1319-25 pubmed publisher
    The neuron-specific potassium-chloride cotransporter 2 (KCC2) plays a crucial role in adjusting intracellular Cl(-) concentrations...
  8. Lu Y, Zheng J, Xiong L, Zimmermann M, Yang J. Spinal cord injury-induced attenuation of GABAergic inhibition in spinal dorsal horn circuits is associated with down-regulation of the chloride transporter KCC2 in rat. J Physiol. 2008;586:5701-15 pubmed publisher
    ..b>KCC2 is an isoform of the K(+)-Cl(-) cotransporter that contributes to the regulation of transmembrane anion gradient ..
  9. Nabekura J, Ueno T, Okabe A, Furuta A, Iwaki T, Shimizu Okabe C, et al. Reduction of KCC2 expression and GABAA receptor-mediated excitation after in vivo axonal injury. J Neurosci. 2002;22:4412-7 pubmed
    ..In situ hybridization revealed that neuron-specific K(+)-Cl(-) cotransporter (KCC2) mRNA was significantly reduced in the DMV after axotomy compared with that in control neurons...
  10. Miletic G, Miletic V. Loose ligation of the sciatic nerve is associated with TrkB receptor-dependent decreases in KCC2 protein levels in the ipsilateral spinal dorsal horn. Pain. 2008;137:532-9 pubmed
    Significant decreases in the protein levels of potassium-chloride co-transporter 2 (KCC2) were detected in the ipsilateral spinal dorsal horn 4h following loose ligation of the sciatic nerve...
  11. Watanabe M, Wake H, Moorhouse A, Nabekura J. Clustering of neuronal K+-Cl- cotransporters in lipid rafts by tyrosine phosphorylation. J Biol Chem. 2009;284:27980-8 pubmed publisher
    The neuronal K(+)-Cl(-) cotransporter (KCC2) is a membrane transport protein that extrudes Cl(-) from neurons and helps maintain low intracellular [Cl(-)] and hyperpolarizing GABAergic synaptic potentials...
  12. Inoue K, Yamada J, Ueno S, Fukuda A. Brain-type creatine kinase activates neuron-specific K+-Cl- co-transporter KCC2. J Neurochem. 2006;96:598-608 pubmed
    ..This functional switch is primarily attributable to the K+-Cl- co-transporter KCC2, the expression of which is developmentally regulated in neurons...
  13. Mao X, Ma P, Cao D, Sun C, Ji Z, Min D, et al. Altered expression of GABAA receptors (?4, ?2 subunit), potassium chloride cotransporter 2 and astrogliosis in tremor rat hippocampus. Brain Res Bull. 2011;86:373-9 pubmed publisher
    ..GABA(A) receptor (GABA(A)R), potassium chloride cotransporter 2 (KCC2) and astrocytes are of particular importance to GABAergic transmission and thus involved in the development of ..
  14. Choe K, Han S, Gaub P, Shell B, Voisin D, Knapp B, et al. High salt intake increases blood pressure via BDNF-mediated downregulation of KCC2 and impaired baroreflex inhibition of vasopressin neurons. Neuron. 2015;85:549-60 pubmed publisher
    ..through a brain-derived neurotrophic factor (BDNF)-dependent activation of TrkB receptors and downregulation of KCC2 expression, which prevents inhibitory GABAergic signaling...
  15. Hershfinkel M, Kandler K, Knoch M, Dagan Rabin M, Aras M, Abramovitch Dahan C, et al. Intracellular zinc inhibits KCC2 transporter activity. Nat Neurosci. 2009;12:725-7 pubmed publisher
    We found that K(+)/Cl(-) co-transporter 2 (KCC2) activity, monitored with wide-field fluorescence, was inhibited by intracellular Zn(2+), a major component of neuronal injury...
  16. Zhou H, Chen S, Byun H, Chen H, Li L, Han H, et al. N-methyl-D-aspartate receptor- and calpain-mediated proteolytic cleavage of K+-Cl- cotransporter-2 impairs spinal chloride homeostasis in neuropathic pain. J Biol Chem. 2012;287:33853-64 pubmed
    Loss of synaptic inhibition by ?-aminobutyric acid and glycine due to potassium chloride cotransporter-2 (KCC2) down-regulation in the spinal cord is a critical mechanism of synaptic plasticity in neuropathic pain...
  17. Song L, Mercado A, Vazquez N, Xie Q, Desai R, George A, et al. Molecular, functional, and genomic characterization of human KCC2, the neuronal K-Cl cotransporter. Brain Res Mol Brain Res. 2002;103:91-105 pubmed
    The expression level of the neuronal-specific K-Cl cotransporter KCC2 (SLC12A5) is a major determinant of whether neurons will respond to GABA with a depolarizing, excitatory response or a hyperpolarizing, inhibitory response...
  18. 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 ..
  19. Awad P, Sanon N, Chattopadhyaya B, Carriço J, Ouardouz M, Gagné J, et al. Reducing premature KCC2 expression rescues seizure susceptibility and spine morphology in atypical febrile seizures. Neurobiol Dis. 2016;91:10-20 pubmed publisher
    ..The mechanisms linking these events are currently poorly understood. Potassium-chloride cotransporter KCC2 affects several aspects of neuronal circuit development and function, by modulating GABAergic transmission and ..
  20. Zhang Z, Wang X, Wang W, Lu Y, Pan Z. Brain-derived neurotrophic factor-mediated downregulation of brainstem K+-Cl- cotransporter and cell-type-specific GABA impairment for activation of descending pain facilitation. Mol Pharmacol. 2013;84:511-20 pubmed publisher
    ..inflammatory pain induced by complete Freund's adjuvant decreased the protein level of K(+)-Cl(-) cotransporter (KCC2) in both total and synaptosomal preparations...
  21. Kovacs K, Basu K, Rouiller I, Sik A. Regional differences in the expression of K(+)-Cl(-) 2 cotransporter in the developing rat cortex. Brain Struct Funct. 2014;219:527-38 pubmed publisher
    The type 2 potassium-chloride cotransporter (KCC2) is the main regulator of intracellular chloride concentration in CNS neurons, and plays a crucial role in spine development that is independent of its ion cotransport function...
  22. Liu C, Liao W, Chu Y, Yang C, Chen K, Wu C, et al. Pulsed Radiofrequency Attenuates Complete Freund's Adjuvant-Induced Epigenetic Suppression of Potassium Chloride Cotransporter 2 Expression. Pain Med. 2017;18:807-813 pubmed publisher
    ..Epigenetic modification of potassium-chloride cotransporter 2 (KCC2) gene expression was examined to elucidate the potential contributing mechanism...
  23. Chevy Q, Heubl M, Goutierre M, Backer S, Moutkine I, Eugène E, et al. KCC2 Gates Activity-Driven AMPA Receptor Traffic through Cofilin Phosphorylation. J Neurosci. 2015;35:15772-86 pubmed publisher
    Expression of the neuronal K/Cl transporter KCC2 is tightly regulated throughout development and by both normal and pathological neuronal activity...
  24. Hamidi S, Avoli M. KCC2 function modulates in vitro ictogenesis. Neurobiol Dis. 2015;79:51-8 pubmed publisher
    ..The efficacy of inhibition relies on low levels of intracellular Cl(-), which are controlled by KCC2 activity...
  25. Titz S, Sammler E, Hormuzdi S. Could tuning of the inhibitory tone involve graded changes in neuronal chloride transport?. Neuropharmacology. 2015;95:321-31 pubmed publisher
    ..through GABAA and glycine receptors depends on the presence of the neuronal cation-chloride-cotransporter protein, KCC2. Several transcriptional and post-transcriptional mechanisms have been shown to regulate KCC2 and thereby influence ..
  26. Côté M, Gandhi S, Zambrotta M, Houle J. Exercise modulates chloride homeostasis after spinal cord injury. J Neurosci. 2014;34:8976-87 pubmed publisher
    ..chloride concentration, which is determined largely by the expression of two cation-chloride cotransporters (CCCs), KCC2 and NKCC1, which serve as chloride exporters and importers, respectively...
  27. Yeo M, Berglund K, Hanna M, Guo J, Kittur J, Torres M, et al. Bisphenol A delays the perinatal chloride shift in cortical neurons by epigenetic effects on the Kcc2 promoter. Proc Natl Acad Sci U S A. 2013;110:4315-20 pubmed publisher
    ..led to delay in the perinatal chloride shift caused by significant decrease in potassium chloride cotransporter 2 (Kcc2) mRNA expression in developing rat, mouse, and human cortical neurons. Neuronal chloride increased correspondingly...
  28. Gillen C, Brill S, Payne J, Forbush B. Molecular cloning and functional expression of the K-Cl cotransporter from rabbit, rat, and human. A new member of the cation-chloride cotransporter family. J Biol Chem. 1996;271:16237-44 pubmed
    ..These data demonstrate that the KCC1 cDNAs encode a widely expressed K-Cl cotransporter with the characteristics of the K-Cl transporter that has been characterized in red cells...
  29. Tang D, Qian A, Song D, Ben Q, Yao W, Sun J, et al. Role of the potassium chloride cotransporter isoform 2-mediated spinal chloride homeostasis in a rat model of visceral hypersensitivity. Am J Physiol Gastrointest Liver Physiol. 2015;308:G767-78 pubmed publisher
    ..of WAS exposure, levels of both total protein and the oligomeric form of the K(+)-Cl(-) cotransporter isoform 2 (KCC2), but not Na(+)-K(+)-2Cl(-) transporter isoform 1 (NKCC1), were significantly decreased in the dorsal horn of the ..
  30. 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...
  31. Titz S, Hormuzdi S, Lewen A, Monyer H, Misgeld U. Intracellular acidification in neurons induced by ammonium depends on KCC2 function. Eur J Neurosci. 2006;23:454-64 pubmed
    The Cl(-)-extruding neuron-specific K(+)-Cl(-) cotransporter KCC2, which establishes hyperpolarizing inhibition, can transport NH(4) (+) instead of K(+)...
  32. Garbarini N, Delpire E. The RCC1 domain of protein associated with Myc (PAM) interacts with and regulates KCC2. Cell Physiol Biochem. 2008;22:31-44 pubmed publisher
    ..The neuron-specific electroneutral potassium (K(+)) and chloride (Cl(-)) cotransporter (KCC2), is a key regulator of neuronal Cl(-), yet little is known about KCC2 regulation...
  33. Liu Q, Wong Riley M. Postnatal development of Na(+)-K(+)-2Cl(-) co-transporter 1 and K(+)-Cl(-) co-transporter 2 immunoreactivity in multiple brain stem respiratory nuclei of the rat. Neuroscience. 2012;210:1-20 pubmed publisher
    ..Since Na(+)-K(+)-2Cl(-) co-transporter 1 (NKCC1) and K(+)-Cl(-) co-transporter 2 (KCC2) play pivotal roles in determining the responses of GABA(A) and glycine receptors, we hypothesized that NKCC1 and ..
  34. 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
    ..chloride (Cl-) concentration, which is maintained by the potassium-chloride cotransporter KCC2 (encoded by Slc12a5)...
  35. Sterley T, Howells F, Dimatelis J, Russell V. Genetic predisposition and early life experience interact to determine glutamate transporter (GLT1) and solute carrier family 12 member 5 (KCC2) levels in rat hippocampus. Metab Brain Dis. 2016;31:169-82 pubmed
    ..Our findings show that solute carrier family 12 member 5 (KCC2) is increased in SHR hippocampus...
  36. Williams J, Payne J. Cation transport by the neuronal K(+)-Cl(-) cotransporter KCC2: thermodynamics and kinetics of alternate transport modes. Am J Physiol Cell Physiol. 2004;287:C919-31 pubmed
    ..We hypothesized that these two cations altered the operation of the neuronal K(+)-Cl(-) cotransporter (KCC2)...
  37. Hartmann A, Blaesse P, Kranz T, Wenz M, Schindler J, Kaila K, et al. Opposite effect of membrane raft perturbation on transport activity of KCC2 and NKCC1. J Neurochem. 2009;111:321-31 pubmed publisher
    ..is set by the activity of the Na(+)-K(+)-2Cl(-) cotransporter (NKCC1) and the K(+)-Cl(-) cotransporter (KCC2). Here, we investigated the cotransporters' functional dependence on membrane rafts...
  38. Gulacsi A, Lee C, Sik A, Viitanen T, Kaila K, Tepper J, et al. Cell type-specific differences in chloride-regulatory mechanisms and GABA(A) receptor-mediated inhibition in rat substantia nigra. J Neurosci. 2003;23:8237-46 pubmed
    ..Light-microscopic immunocytochemistry revealed that the potassium-chloride cotransporter 2 (KCC2) was localized only in the dendrites of nondopaminergic (primarily GABAergic) neurons in the substantia nigra, ..
  39. Murguía Castillo J, Beas Zarate C, Rivera Cervantes M, Feria Velasco A, Ureña Guerrero M. NKCC1 and KCC2 protein expression is sexually dimorphic in the hippocampus and entorhinal cortex of neonatal rats. Neurosci Lett. 2013;552:52-7 pubmed publisher
    ..GABA-mediated excitation has been observed when the NKCC1 (chloride importer) expression level is higher than KCC2 (chloride exporter)...
  40. Inoue K, Furukawa T, Kumada T, Yamada J, Wang T, Inoue R, et al. Taurine inhibits K+-Cl- cotransporter KCC2 to regulate embryonic Cl- homeostasis via with-no-lysine (WNK) protein kinase signaling pathway. J Biol Chem. 2012;287:20839-50 pubmed publisher
    GABA inhibits mature neurons and conversely excites immature neurons due to lower K(+)-Cl(-) cotransporter 2 (KCC2) expression...
  41. Gauvain G, Chamma I, Chevy Q, Cabezas C, Irinopoulou T, Bodrug N, et al. The neuronal K-Cl cotransporter KCC2 influences postsynaptic AMPA receptor content and lateral diffusion in dendritic spines. Proc Natl Acad Sci U S A. 2011;108:15474-9 pubmed publisher
    The K-Cl cotransporter KCC2 plays an essential role in neuronal chloride homeostasis, and thereby influences the efficacy and polarity of GABA signaling...
  42. Morgado C, Pinto Ribeiro F, Tavares I. Diabetes affects the expression of GABA and potassium chloride cotransporter in the spinal cord: a study in streptozotocin diabetic rats. Neurosci Lett. 2008;438:102-6 pubmed publisher
    ..of GABA, its synthesizing enzyme glutamic acid decarboxylase (GAD) and the potassium chloride cotransporter (KCC2), in the spinal dorsal horn of streptozotocin (STZ)-induced diabetic rats...
  43. Winkelmann A, Semtner M, Meier J. Chloride transporter KCC2-dependent neuroprotection depends on the N-terminal protein domain. Cell Death Dis. 2015;6:e1776 pubmed publisher
    ..Downregulation of the chloride transporter KCC2 in the epileptic tissue may not only affect regulation of the polarity of GABAergic synaptic transmission but also ..
  44. Döding A, Hartmann A, Beyer T, Nothwang H. KCC2 transport activity requires the highly conserved L??? in the C-terminal ?1 strand. Biochem Biophys Res Commun. 2012;420:492-7 pubmed publisher
    The activity of the neuron-specific K(+), Cl(-) co-transporter 2 (KCC2) is required for hyperpolarizing action of GABA and glycine. KCC2-mediated transport therefore plays a pivotal role in neuronal inhibition...
  45. Casula S, Shmukler B, Wilhelm S, Stuart Tilley A, Su W, Chernova M, et al. A dominant negative mutant of the KCC1 K-Cl cotransporter: both N- and C-terminal cytoplasmic domains are required for K-Cl cotransport activity. J Biol Chem. 2001;276:41870-8 pubmed
    ..Delta(N)117 also exhibited dominant negative inhibition of human KCC1 and KCC3 and, with lower potency, mouse KCC4 and rat KCC2.
  46. Bergeron M, Gagnon E, Wallendorff B, Lapointe J, Isenring P. Ammonium transport and pH regulation by K(+)-Cl(-) cotransporters. Am J Physiol Renal Physiol. 2003;285:F68-78 pubmed
    ..Indeed, NKCC2, KCC1, KCC2, and KCC3 are inhibited at intracellular pH <7.5, whereas KCC4 is activated...
  47. de los Heros P, Alessi D, Gourlay R, Campbell D, Deak M, MacArtney T, et al. The WNK-regulated SPAK/OSR1 kinases directly phosphorylate and inhibit the K+-Cl- co-transporters. Biochem J. 2014;458:559-73 pubmed publisher
    ..also observe that KCCs are directly phosphorylated by SPAK/OSR1, at a novel Site-3 (Thr5 in KCC1/KCC3 and Thr6 in KCC2/KCC4), and a previously recognized KCC3-specific residue, Site-4 (Ser96)...
  48. Galanopoulou A, Kyrozis A, Claudio O, Stanton P, Moshe S. Sex-specific KCC2 expression and GABA(A) receptor function in rat substantia nigra. Exp Neurol. 2003;183:628-37 pubmed
    ..neurons depending upon the level of expression of the neuronal specific potassium chloride contransporter KCC2. We studied KCC2 mRNA expression in the SNR as a function of sex and age and correlated KCC2 expression with the in ..
  49. Shimizu Okabe C, Okabe A, Kilb W, Sato K, Luhmann H, Fukuda A. Changes in the expression of cation-Cl- cotransporters, NKCC1 and KCC2, during cortical malformation induced by neonatal freeze-lesion. Neurosci Res. 2007;59:288-95 pubmed
    ..situ hybridization histochemistry for cation-Cl(-) cotrtansporters, that NKCC1 mRNA expression was upregulated and KCC2 mRNA expression downregulated at P4 in "bridge" structure (formed in lesion site across the gap in intact ..
  50. Perrot Sinal T, Sinal C, Reader J, Speert D, McCarthy M. Sex differences in the chloride cotransporters, NKCC1 and KCC2, in the developing hypothalamus. J Neuroendocrinol. 2007;19:302-8 pubmed
    ..Here, we investigate the expression of the chloride cotransporters, NKCC1 (Na-K-2Cl(-)) and KCC2 (K-Cl(-)) in neonate mediobasal hypothalamus of male and female rats...
  51. 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...
  52. Ouardouz M, Sastry B. Activity-mediated shift in reversal potential of GABA-ergic synaptic currents in immature neurons. Brain Res Dev Brain Res. 2005;160:78-84 pubmed
    ..Thus, maturation of the GABA response may rely on an activity-dependent up-regulation of KCC-2. ..
  53. Wu H, Shao A, Zhao M, Chen S, Yu J, Zhou J, et al. Melatonin attenuates neuronal apoptosis through up-regulation of K(+) -Cl(-) cotransporter KCC2 expression following traumatic brain injury in rats. J Pineal Res. 2016;61:241-50 pubmed publisher
    ..The neuron-specific K(+) -Cl(-) cotransporter-2 (KCC2), the principal Cl(-) extruder in adult neurons, plays an important role in Cl(-) homeostasis and neuronal function...
  54. Fiumelli H, Cancedda L, Poo M. Modulation of GABAergic transmission by activity via postsynaptic Ca2+-dependent regulation of KCC2 function. Neuron. 2005;48:773-86 pubmed
    ..Activity- and Ca2+-induced E(Cl) shifts were larger in mature neurons, which express the K-Cl cotransporter KCC2 at high levels, and inhibition of KCC2 occluded the shifts...
  55. Inoue K, Ueno S, Fukuda A. Interaction of neuron-specific K+-Cl- cotransporter, KCC2, with brain-type creatine kinase. FEBS Lett. 2004;564:131-5 pubmed
    ..This functional change is primarily attributable to a K(+)-Cl(-) cotransporter, KCC2, the expression of which is developmentally regulated in neurons...
  56. Yang K, Huang Z, Huang J, Zhang X, Xiao B. Expression of the neuron-specific potassium chloride cotransporter KCC2 in adult rat cochlear. Neurosci Lett. 2008;441:205-9 pubmed publisher
    ..GABA is a proven inhibitory neurotransmitter in the efferent systems in mammalian cochlear. KCC2 is a neuron-specific potassium chloride cotransporter whose role in mature central neurons is to maintain the low ..
  57. 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, ..
  58. Stödberg T, McTague A, Ruiz A, Hirata H, Zhen J, Long P, et al. Mutations in SLC12A5 in epilepsy of infancy with migrating focal seizures. Nat Commun. 2015;6:8038 pubmed publisher
    The potassium-chloride co-transporter KCC2, encoded by SLC12A5, plays a fundamental role in fast synaptic inhibition by maintaining a hyperpolarizing gradient for chloride ions...
  59. 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...
  60. Baroncelli L, Cenni M, Melani R, Deidda G, Landi S, Narducci R, et al. Early IGF-1 primes visual cortex maturation and accelerates developmental switch between NKCC1 and KCC2 chloride transporters in enriched animals. Neuropharmacology. 2017;113:167-177 pubmed publisher
    ..Early IGF-1 decreased the ratio between the expression of NKCC1 and KCC2 cation/chloride transporters, and the reversal potential for GABAAR-driven Cl- currents (E<..
  61. Toyoda H, Yamada J, Ueno S, Okabe A, Kato H, Sato K, et al. Differential functional expression of cation-Cl- cotransporter mRNAs (KCC1, KCC2, and NKCC1) in rat trigeminal nervous system. Brain Res Mol Brain Res. 2005;133:12-8 pubmed
    ..are distributed in the trigeminal nuclei, we investigated the expressions of K+-Cl- cotransporters (KCC1 and KCC2) and Na+-K+-2Cl- cotransporter (NKCC1) mRNAs by using in situ hybridization histochemistry...
  62. Matrisciano F, Nasca C, Molinaro G, Riozzi B, Scaccianoce S, Raggi M, et al. Enhanced expression of the neuronal K+/Cl- cotransporter, KCC2, in spontaneously depressed Flinders Sensitive Line rats. Brain Res. 2010;1325:112-20 pubmed publisher
    ..examined whether FSL rats differed from control rats for the expression levels of the K(+)/Cl(-) cotransporter, KCC2, which transports Cl(-) ions out of neurons, thus creating the concentration gradient that allows Cl(-) influx ..
  63. Strange K, Singer T, Morrison R, Delpire E. Dependence of KCC2 K-Cl cotransporter activity on a conserved carboxy terminus tyrosine residue. Am J Physiol Cell Physiol. 2000;279:C860-7 pubmed
    ..To date, four mammalian KCC genes have been identified. KCC2 is expressed exclusively in neurons...
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    The neuronal K-Cl cotransporter isoform (KCC2) was functionally expressed in human embryonic kidney (HEK-293) cell lines...
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    ..In conditions of neuronal damage, where neuronal excitability is increased, the expression of the KCC2 transporter is decreased. This is also seen in spinal cord in models of neuropathic pain...