SLC12A5

Summary

Gene Symbol: SLC12A5
Description: solute carrier family 12 member 5
Alias: EIEE34, EIG14, KCC2, hKCC2, solute carrier family 12 member 5, K-Cl cotransporter 2, electroneutral potassium-chloride cotransporter 2, erythroid K-Cl cotransporter 2, neuronal K-Cl cotransporter, solute carrier family 12 (potassium/chloride transporter), member 5
Species: human
Products:     SLC12A5

Top Publications

  1. 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...
  2. Cruz Rangel S, Melo Z, Vazquez N, Meade P, Bobadilla N, Pasantes Morales H, et al. Similar effects of all WNK3 variants on SLC12 cotransporters. Am J Physiol Cell Physiol. 2011;301:C601-8 pubmed publisher
    ..That is, NKCC1/2 and NCC were inhibited, even in hypertonicity, while KCCs were activated, even in isotonic conditions. We conclude that the effects of all WNK3 variants toward SLC12 proteins are similar. ..
  3. Jaggi A, Kaur A, Bali A, Singh N. Expanding Spectrum of Sodium Potassium Chloride Co-transporters in the Pathophysiology of Diseases. Curr Neuropharmacol. 2015;13:369-88 pubmed
    ..In the early developing brain, GABAA activation primarily produces excitatory actions due to high NKCC1/KCC2 ratio...
  4. Chugh D, Ali I, Bakochi A, Bahonjic E, Etholm L, Ekdahl C. Alterations in Brain Inflammation, Synaptic Proteins, and Adult Hippocampal Neurogenesis during Epileptogenesis in Mice Lacking Synapsin2. PLoS ONE. 2015;10:e0132366 pubmed publisher
    ..an increase in the inhibitory adhesion molecules neuroligin-2 and neurofascin and potassium chloride co-transporter KCC2. Decreased expression of γ-aminobutyric acid receptor-δ subunit and cholecystokinin was also evident...
  5. Ju L, Yang J, Gravenstein N, Seubert C, Morey T, Sumners C, et al. Role of environmental stressors in determining the developmental outcome of neonatal anesthesia. Psychoneuroendocrinology. 2017;81:96-104 pubmed publisher
    ..hypothalamic NKCC1 mRNA and corticotropin releasing hormone (CRH) mRNA and decreased K+-2Cl- (KCC2) mRNA levels with greater changes in males...
  6. 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 ..
  7. Yang J, Ju L, Jia M, Zhang H, Sun X, Ji M, et al. Subsequent maternal separation exacerbates neurobehavioral abnormalities in rats neonatally exposed to sevoflurane anesthesia. Neurosci Lett. 2017;661:137-142 pubmed publisher
    ..Rats that were exposed to sevoflurane had decreased hypothalamic K+-2Cl- (KCC2) mRNA level (F(2,13)=3.839, P=0.049), increased NKCC1/KCC2 mRNA ratio (F(2,13)=5.043, P=0...
  8. 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...
  9. Hu D, Yu Z, Zhang Y, Han Y, Zhang W, Lu L, et al. Bumetanide treatment during early development rescues maternal separation-induced susceptibility to stress. Sci Rep. 2017;7:11878 pubmed publisher
    ..1 (NKCC1) on postnatal day 14, and increased the expression of K+/2Cl- cotransporter 2 (KCC2) and γ-aminobutyric acid A (GABAA) receptor subunits on postnatal day 40 in the hippocampus...

More Information

Publications119 found, 100 shown here

  1. Bagla S, Cukovic D, Asano E, Sood S, Luat A, Chugani H, et al. A distinct microRNA expression profile is associated with α[11C]-methyl-L-tryptophan (AMT) PET uptake in epileptogenic cortical tubers resected from patients with tuberous sclerosis complex. Neurobiol Dis. 2018;109:76-87 pubmed publisher
    ..The microRNAs target a group of genes enriched for synaptic signaling and epilepsy risk, including SLC12A5, SYT1, GRIN2A, GRIN2B, KCNB1, SCN2A, TSC1, and MEF2C...
  2. Bai Y, Bai Y, Wang S, Wu F, Wang D, Chen J, et al. Targeted upregulation of uncoupling protein 2 within the basal ganglia output structure ameliorates dyskinesia after severe liver failure. Free Radic Biol Med. 2018;124:40-50 pubmed publisher
    ..The modulatory effects of UCP2 was due to mediation of K+-Cl- cotransporter-2 (KCC2) expression on GABAergic neurons of SNr...
  3. Kitayama T, Morita K, Motoyama N, Dohi T. Down-regulation of zinc transporter-1 in astrocytes induces neuropathic pain via the brain-derived neurotrophic factor - K+-Cl- co-transporter-2 signaling pathway in the mouse spinal cord. Neurochem Int. 2016;101:120-131 pubmed publisher
    ..The down-regulated expression of KCC2 in spinal cord was induced by ZnT1 KD and prevented by an intrathecal injection of IL-6, BDNF, and TrkB siRNA...
  4. Mu X, Wang H, Cheng X, Yang L, Sun X, Qu H, et al. Inhibition of Nkcc1 promotes axonal growth and motor recovery in ischemic rats. Neuroscience. 2017;365:83-93 pubmed publisher
    ..Nogo-A, NKCC1, KCC2 and BDNF in the perilesional cortex and BDA, PSD-95 and vGlut1 in the denervated spinal cord were measured by ..
  5. Kim J, Kobayashi S, Shimizu Okabe C, Okabe A, Moon C, Shin T, et al. Changes in the expression and localization of signaling molecules in mouse facial motor neurons during regeneration of facial nerves. J Chem Neuroanat. 2018;88:13-21 pubmed publisher
    ..ChAT), galanin, calcitonin gene-related protein (CGRP), gephyrin, and potassium chloride co-transporter 2 (KCC2) in the facial motor neurons after surgery until recovery...
  6. Wang F, Wang X, Shapiro L, Cotrina M, Liu W, Wang E, et al. NKCC1 up-regulation contributes to early post-traumatic seizures and increased post-traumatic seizure susceptibility. Brain Struct Funct. 2017;222:1543-1556 pubmed publisher
    ..cotransporter 1 (NKCC1) and K+-Cl--cotransporter 2 (KCC2)...
  7. López Álvarez V, Mòdol L, Navarro X, Cobianchi S. Early increasing-intensity treadmill exercise reduces neuropathic pain by preventing nociceptor collateral sprouting and disruption of chloride cotransporters homeostasis after peripheral nerve injury. Pain. 2015;156:1812-25 pubmed publisher
    ..Na⁺-K⁺-2Cl⁻ cotransporter 1 (NKCC1) upregulation in DRG, and K⁺-Cl⁻ cotransporter 2 (KCC2) downregulation in lumbar spinal cord dorsal horn...
  8. Kim Y, Kim W, Jung W, Jin X, Kim Y, Kim B, et al. Excitatory GABAergic Action and Increased Vasopressin Synthesis in Hypothalamic Magnocellular Neurosecretory Cells Underlie the High Plasma Level of Vasopressin in Diabetic Rats. Diabetes. 2018;67:486-495 pubmed publisher
    ..isotype 1 (a Cl- importer) was upregulated and K+-Cl- cotransporter isotype 2 (KCC2; a Cl- extruder) was downregulated in STZ rats...
  9. Sasaki Russell J, Chinn G, Maharjan D, Eichbaum Y, Sall J. Female rats are more vulnerable to lasting cognitive impairment after isoflurane exposure on postnatal day 4 than 7. Br J Anaesth. 2019;122:490-499 pubmed publisher
    ..by Fluoro-Jade C staining in select brain regions, and developmental expression of the chloride transporters KCC2 and NKCC1 was analysed by immunoblotting in male and female rats at P4 and P7...
  10. 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)...
  11. Yang G, Zhou X, An X, Liu X, Zhang Y, Yu D. Synergistic effect of mild hypothermia and the Notch inhibitor DAPT against post stroke seizures. Biomed Pharmacother. 2017;96:675-684 pubmed publisher
    ..synaptic neurotransmission by down-regulating gamma amino acid, butyric acid (GABA), and the cotransporter, KCC2. DAPT treatment normalized the homeostasis of excitatory and inhibitory synaptic neurotransmission, suggesting that ..
  12. Ring H, Mendu S, Shirazi Fard S, Birnir B, Hallböök F. GABA maintains the proliferation of progenitors in the developing chick ciliary marginal zone and non-pigmented ciliary epithelium. PLoS ONE. 2012;7:e36874 pubmed publisher
    ..The NPE cells had low levels of the Cl-transporter KCC2 compared to the mature retina, suggesting a depolarising role for the GABA(A) receptors...
  13. Zhang W, Schmelzeisen S, Parthier D, Frings S, Möhrlen F. Anoctamin Calcium-Activated Chloride Channels May Modulate Inhibitory Transmission in the Cerebellar Cortex. PLoS ONE. 2015;10:e0142160 pubmed publisher
    ..Thus, in balance with the chloride extrusion mechanism via the co-transporter KCC2, ANO2 appears to regulate ionic plasticity in the cerebellum.
  14. Kourdougli N, Varpula S, Chazal G, Rivera C. Detrimental effect of post Status Epilepticus treatment with ROCK inhibitor Y-27632 in a pilocarpine model of temporal lobe epilepsy. Front Cell Neurosci. 2015;9:413 pubmed publisher
    ..with Y-27632 exacerbates the down-regulation and pathological distribution of the K(+)-Cl(-) cotransporter KCC2, thus providing a putative mechanism for post SE induced neuronal death...
  15. Subramanian D, Pralong E, Daniel R, Chacko A, Stoop R, Babu K. Gamma oscillatory activity in vitro: a model system to assess pathophysiological mechanisms of comorbidity between autism and epilepsy. Transl Psychiatry. 2018;8:16 pubmed publisher
    ..spectrum, their origin (in the CA1), and their sensitivity to blockers of cation-chloride pumps (NKCC1 and KCC2), as well as to oxytocin...
  16. Kahle K, Schmouth J, Lavastre V, Latremoliere A, Zhang J, Andrews N, et al. Inhibition of the kinase WNK1/HSN2 ameliorates neuropathic pain by restoring GABA inhibition. Sci Signal. 2016;9:ra32 pubmed publisher
    ..of neuropathic pain, WNK1/HSN2 contributed to a maladaptive decrease in the activity of the K(+)-Cl(-)cotransporter KCC2 by increasing its inhibitory phosphorylation at Thr(906)and Thr(1007), resulting in an associated loss of GABA (γ-..
  17. Ruffolo G, Iyer A, Cifelli P, Roseti C, Mühlebner A, van Scheppingen J, et al. Functional aspects of early brain development are preserved in tuberous sclerosis complex (TSC) epileptogenic lesions. Neurobiol Dis. 2016;95:93-101 pubmed publisher
    ..receptor subunits (GABAA α1-5, β3, γ2, δ; GluA1, GluA2) and cation chloride co-transporters NKCC1 and KCC2. The evaluation of nine human cortical brain samples, from 15 gestation weeks to 15years old, showed a progressive ..
  18. Huberfeld G, Blauwblomme T, Miles R. Hippocampus and epilepsy: Findings from human tissues. Rev Neurol (Paris). 2015;171:236-51 pubmed publisher
    ..of the cotransporters regulating intracellular chloride concentration, the importer NKCC1 and the extruder KCC2. Blockade of NKCC1 actions by the diuretic bumetanide restores intracellular chloride and thus hyperpolarizing ..
  19. Chen S, Zhu L, Chen H, Wen L, Laumet G, Pan H. Increased spinal cord Na⁺-K⁺-2Cl⁻ cotransporter-1 (NKCC1) activity contributes to impairment of synaptic inhibition in paclitaxel-induced neuropathic pain. J Biol Chem. 2014;289:31111-20 pubmed publisher
    ..Cation-chloride cotransporters, such as Na(+)-K(+)-2Cl(-) cotransporter-1 (NKCC1) and K(+)-Cl(-) cotransporter-2 (KCC2), critically influence spinal synaptic inhibition by regulating intracellular chloride concentrations...
  20. Huang Y, Lee K, Murphy L, Garraway S, Grau J. Acute spinal cord injury (SCI) transforms how GABA affects nociceptive sensitization. Exp Neurol. 2016;285:82-95 pubmed publisher
    ..The effect of SCI on GABA function was linked to a reduction in the Cl- transporter, KCC2, leading to a reduction in intracellular Cl- that would attenuate GABA-mediated inhibition...
  21. Wu J, Hocevar M, Bie B, Foss J, Naguib M. Cannabinoid Type 2 Receptor System Modulates Paclitaxel-Induced Microglial Dysregulation and Central Sensitization in Rats. J Pain. 2018;: pubmed publisher
    ..The CB2 agonist MDA7 alleviated these pathological processes. MDA7 represents an innovative therapeutic approach for treatment of chemotherapy-induced neuropathy. ..
  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. Baek H, Yi M, Pandit S, Park J, Kwon H, Zhang E, et al. Altered expression of KCC2 in GABAergic interneuron contributes prenatal stress-induced epileptic spasms in infant rat. Neurochem Int. 2016;97:57-64 pubmed publisher
    ..Prenatal stress markedly decreased the expression of K(+)/Cl(-) co-transporter (KCC2) in the cortex...
  24. Wang Y, Summers T, Peterson W, Miiller E, Burrell B. Differential effects of GABA in modulating nociceptive vs. non-nociceptive synapses. Neuroscience. 2015;298:397-409 pubmed publisher
    ..VU 0240551 (VU), an inhibitor of the Cl(-) exporter K-Cl co-transporter isoform 2 (KCC2), attenuated GABA-mediated hyperpolarization of the non-nociceptive afferent while bumetanide (BUM), an inhibitor ..
  25. Kim J, Takayama C, Park C, Ahn M, Moon C, Shin T. Immunohistochemical localization of GABAergic key molecules in the main olfactory bulb of the Korean roe deer, Capreolus pygargus. Acta Histochem. 2015;117:642-8 pubmed publisher
    ..GABA transporter (VGAT), GABA transporters (GATs; GAT-1 and GAT-3), and potassium sodium chloride co-transporter 2 (KCC2)...
  26. Okada Ogawa A, Nakaya Y, Imamura Y, Kobayashi M, Shinoda M, Kita K, et al. Involvement of medullary GABAergic system in extraterritorial neuropathic pain mechanisms associated with inferior alveolar nerve transection. Exp Neurol. 2015;267:42-52 pubmed publisher
    ..Furthermore, the expression of potassium-chloride co-transporter 2 (KCC2) in the Vc was significantly reduced in IANX rats compared with sham rats...
  27. Tian Y, Guo S, Li J, DU H, Wang C, Zhang J, et al. Topiramate attenuates early brain injury following subarachnoid haemorrhage in rats via duplex protection against inflammation and neuronal cell death. Brain Res. 2015;1622:174-85 pubmed publisher
    ..GABA)-ergic signalling molecules, GABAA receptor (GABAAR) α1, GABAAR γ2, and K(+)-Cl(-) co-transporter 2 (KCC2) together and downregulated Na(+)-K(+)-Cl(-) co-transporter 1 (NKCC1) expression...
  28. Ehrlich D, Neigh G, Bourke C, Nemeth C, Hazra R, Ryan S, et al. Prenatal stress, regardless of concurrent escitalopram treatment, alters behavior and amygdala gene expression of adolescent female rats. Neuropharmacology. 2015;97:251-8 pubmed publisher
    ..behavior in adolescent females and profoundly influenced amygdala expression of the chloride transporters KCC2 and NKCC1, which regulate GABAergic function...
  29. Stamboulian Platel S, Legendre A, Chabrol T, Platel J, Pernot F, Duveau V, et al. Activation of GABAA receptors controls mesiotemporal lobe epilepsy despite changes in chloride transporters expression: In vivo and in silico approach. Exp Neurol. 2016;284:11-28 pubmed publisher
    ..we showed that the expression of the transporter NKCC1, which load neurons with chloride, was increased, whereas KCC2, a chloride extruder, was decreased and that HPDs were suppressed by injection of blockers of NKCC1...
  30. Kahle K, Khanna A, Duan J, Staley K, Delpire E, Poduri A. The KCC2 Cotransporter and Human Epilepsy: Getting Excited About Inhibition. Neuroscientist. 2016;22:555-562 pubmed
    The cation-Cl- cotransporter KCC2, encoded by SLC12A5, is required for the emergence and maintenance of GABAergic fast synaptic inhibition in organisms across evolution...
  31. Ostroumov A, Thomas A, Kimmey B, Karsch J, Doyon W, Dani J. Stress Increases Ethanol Self-Administration via a Shift toward Excitatory GABA Signaling in the Ventral Tegmental Area. Neuron. 2016;92:493-504 pubmed publisher
    ..and involved stress-induced functional downregulation of the K+, Cl- cotransporter, KCC2. Blocking stress hormone receptors, enhancing KCC2 function, or preventing excitatory GABA signaling by alternative ..
  32. Agez M, Schultz P, Medina I, Baker D, Burnham M, Cardarelli R, et al. Molecular architecture of potassium chloride co-transporter KCC2. Sci Rep. 2017;7:16452 pubmed publisher
    b>KCC2 is a neuron specific K+-Cl- co-transporter that controls neuronal chloride homeostasis, and is critically involved in many neurological diseases including brain trauma, epilepsies, autism and schizophrenia...
  33. Singh R, Dagar P, Pal S, Basu B, Shankar B. Significant alterations of the novel 15 gene signature identified from macrophage-tumor interactions in breast cancer. Biochim Biophys Acta Gen Subj. 2018;1862:669-683 pubmed publisher
    ..IL-6, MMP1, MMP9, TGF-?1, TGF-?RII, EGFR) significantly co-occurred with TP53 mutation, WTAPP1 deletion and SLC12A5 amplification along with differential expression of PSAT1 and ESR1 at the mRNA level and TPD52and PRKCD at the ..
  34. Klein P, Lu A, Harper M, McKown H, Morgan J, Beenhakker M. Tenuous Inhibitory GABAergic Signaling in the Reticular Thalamus. J Neurosci. 2018;38:1232-1248 pubmed publisher
    ..Cl- transporters, including KCC2, and extracellular impermeant anions ([A]o) of the extracellular matrix are both proposed to be ..
  35. 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<..
  36. Ludwig A, Rivera C, Uvarov P. A noninvasive optical approach for assessing chloride extrusion activity of the K-Cl cotransporter KCC2 in neuronal cells. BMC Neurosci. 2017;18:23 pubmed publisher
    ..CCCs) are indispensable for maintaining chloride homeostasis in multiple cell types, but K-Cl cotransporter KCC2 is the only CCC member with an exclusively neuronal expression in mammals...
  37. Sivakumaran S, Cardarelli R, Maguire J, Kelley M, Silayeva L, Morrow D, et al. Selective inhibition of KCC2 leads to hyperexcitability and epileptiform discharges in hippocampal slices and in vivo. J Neurosci. 2015;35:8291-6 pubmed publisher
    ..The K(+)/Cl(-) cotransporter KCC2 is the main mechanism by which neurons establish low intracellular Cl(-) levels, which is thought to enable ..
  38. 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...
  39. 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 ..
  40. Yelhekar T, Druzin M, Johansson S. Contribution of Resting Conductance, GABAA-Receptor Mediated Miniature Synaptic Currents and Neurosteroid to Chloride Homeostasis in Central Neurons. Eneuro. 2017;4: pubmed publisher
    ..contributes significantly, in the same order of magnitude as does K+-Cl- cotransporter 2 (KCC2), to [Cl-]i recovery and that Cl- conductance accounts for ? 6% of the total ..
  41. Lin C, Cheng J, Wu C, Chen K, Liu C. Epigenetic suppression of potassium-chloride co-transporter 2 expression in inflammatory pain induced by complete Freund's adjuvant (CFA). Eur J Pain. 2017;21:309-321 pubmed publisher
    ..purpose of our study was to investigate the role of epigenetic modification on potassium-chloride co-transporter 2 (KCC2) gene expression in the persistence of inflammatory pain...
  42. Friedel P, Ludwig A, Pellegrino C, Agez M, Jawhari A, Rivera C, et al. A Novel View on the Role of Intracellular Tails in Surface Delivery of the Potassium-Chloride Cotransporter KCC2. Eneuro. 2017;4: pubmed publisher
    ..are associated with alterations in the expression and localization of potassium-chloride cotransporter type 2 (KCC2), making KCC2 a critical player in neuronal function and an attractive target for therapeutic treatment...
  43. Knoflach F, Hernandez M, Bertrand D. GABAA receptor-mediated neurotransmission: Not so simple after all. Biochem Pharmacol. 2016;115:10-7 pubmed publisher
    ..chloride concentration is partially regulated by cation-chloride co-transporters (CCCs), in particular NKCC1 and KCC2. The aim of the present commentary is to discuss, in light of the latest findings, potential implications of the ..
  44. Li L, Chen S, Chen H, Wen L, Hittelman W, Xie J, et al. Chloride Homeostasis Critically Regulates Synaptic NMDA Receptor Activity in Neuropathic Pain. Cell Rep. 2016;15:1376-1383 pubmed publisher
    ..Here, we show that intrathecal delivery of K(+)-Cl(-) cotransporter-2 (KCC2) using lentiviral vectors produces a complete and long-lasting reversal of pain hypersensitivity induced by nerve ..
  45. 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...
  46. 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-..
  47. Bode C, Richter F, Spröte C, Brigadski T, Bauer A, Fietz S, et al. Altered postnatal maturation of striatal GABAergic interneurons in a phenotypic animal model of dystonia. Exp Neurol. 2017;287:44-53 pubmed publisher
    ..Therefore, different factors that indicate maturation of GABAergic IN were determined. While mRNA of the KCC2 cation/chloride transporters and the cytosolic carboanhydrase VII, used as markers for the so called GABA switch, ..
  48. 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...
  49. Prager Khoutorsky M, Choe K, Levi D, Bourque C. Role of Vasopressin in Rat Models of Salt-Dependent Hypertension. Curr Hypertens Rep. 2017;19:42 pubmed publisher
    ..that the increase in intracellular chloride was provoked by a decrease in the expression of the chloride exporter KCC2 mediated by local secretion of brain-derived neurotrophic factor and activation of TrkB receptors...
  50. Prieto Martín A, Aroca Aguilar J, Sánchez Sánchez F, Muñoz L, López D, Escribano J, et al. Molecular and neurochemical substrates of the audiogenic seizure strains: The GASH:Sal model. Epilepsy Behav. 2017;71:218-225 pubmed publisher
    ..We studied the K+/Cl- cotransporter KCC2 and β2-GABAA-type receptor (GABAAR) and β3-GABAAR subunit expressions in the GASH:Sal both at rest and after ..
  51. Liu J, Li F, Tang X, Ma J, Mao M, Wu F, et al. Sini powder () decoction alleviates mood disorder of insomnia by regulating cation-chloride cotransporters in hippocampus. Chin J Integr Med. 2015;: pubmed
    ..Na-K-Cl-cotransporter (NKCC1) and K+/Cl- cotransporter (KCC2) in the hippocampus were tested by immunohistochemistry, real-time polymerase chain reaction, and western blot...
  52. Notartomaso S, Mascio G, Scarselli P, Martinello K, Fucile S, Gradini R, et al. Expression of the K+/Cl- cotransporter, KCC2, in cerebellar Purkinje cells is regulated by group-I metabotropic glutamate receptors. Neuropharmacology. 2017;115:51-59 pubmed publisher
    The neuronal K+/Cl- symporter, KCC2, shapes synaptic responses mediated by Cl--permeant GABAA receptors...
  53. Melón L, Hooper A, Yang X, Moss S, Maguire J. Inability to suppress the stress-induced activation of the HPA axis during the peripartum period engenders deficits in postpartum behaviors in mice. Psychoneuroendocrinology. 2018;90:182-193 pubmed publisher
    ..Building on our discovery of a role for the K+/Cl-co-transporter, KCC2, in the GABAergic regulation of CRH neurons in the paraventricular nucleus of the hypothalamus (PVN), critical for ..
  54. Schwale C, Schumacher S, Bruehl C, Titz S, Schlicksupp A, Kokocinska M, et al. KCC2 knockdown impairs glycinergic synapse maturation in cultured spinal cord neurons. Histochem Cell Biol. 2016;145:637-46 pubmed publisher
    ..the transmembrane chloride gradient is changed due to increased expression of the potassium-chloride cotransporter (KCC2), thereby shifting the GABA- and glycine-mediated synaptic currents from mostly excitatory depolarization to ..
  55. 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 ..
  56. Hong S, Jung S, Lee E, Shin K, Yang W, Lee H. DNA methylation-based age prediction from saliva: High age predictability by combination of 7 CpG markers. Forensic Sci Int Genet. 2017;29:118-125 pubmed publisher
    ..cg19671120, cg14361627, cg08928145, cg12757011, and cg07547549 of the SST, CNGA3, KLF14, TSSK6, TBR1, and SLC12A5 genes, respectively) in addition to a cell type-specific CpG marker (cg18384097 of the PTPN7 gene) in an ..
  57. 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...
  58. 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)...
  59. Bräuer M, Frei E, Claes L, Grissmer S, Jäger H. Influence of K-Cl cotransporter activity on activation of volume-sensitive Cl- channels in human osteoblasts. Am J Physiol Cell Physiol. 2003;285:C22-30 pubmed
  60. Saitsu H, Watanabe M, Akita T, Ohba C, Sugai K, Ong W, et al. Impaired neuronal KCC2 function by biallelic SLC12A5 mutations in migrating focal seizures and severe developmental delay. Sci Rep. 2016;6:30072 pubmed publisher
    ..Whole exome sequencing (WES) in ten sporadic and one familial case of EIMFS revealed compound heterozygous SLC12A5 (encoding the neuronal K(+)-Cl(-) co-transporter KCC2) mutations in two families: c...
  61. Koppensteiner P, Galvin C, Ninan I. Development- and experience-dependent plasticity in the dorsomedial habenula. Mol Cell Neurosci. 2016;77:105-112 pubmed publisher
    ..is excitatory in the adult dMHb, which is consistent with the reduced expression of the K-Cl co-transporter KCC2. Given the potential role of the dMHb in aversive behaviors, we examined whether fear conditioning or exposure to ..
  62. Buchin A, Chizhov A, Huberfeld G, Miles R, Gutkin B. Reduced Efficacy of the KCC2 Cotransporter Promotes Epileptic Oscillations in a Subiculum Network Model. J Neurosci. 2016;36:11619-11633 pubmed
    ..Human temporal lobe epilepsy has been associated with dysfunction or loss of the potassium-chloride cotransporter KCC2 in a subset of pyramidal cells in the subiculum, a key structure generating epileptic activities...
  63. Tao R, Li C, Newburn E, Ye T, Lipska B, Herman M, et al. Transcript-specific associations of SLC12A5 (KCC2) in human prefrontal cortex with development, schizophrenia, and affective disorders. J Neurosci. 2012;32:5216-22 pubmed publisher
    The neuron-specific K(+)-Cl(-) cotransporter SLC12A5, also known as KCC2, helps mediate the electrophysiological effects of GABA...
  64. Duarte S, Armstrong J, Roche A, Ortez C, Perez A, O Callaghan M, et al. Abnormal expression of cerebrospinal fluid cation chloride cotransporters in patients with Rett syndrome. PLoS ONE. 2013;8:e68851 pubmed publisher
    ..Our aim was to analyse the expression of two relevant CCCs, NKCC1 and KCC2, in the cerebrospinal fluid of Rett syndrome patients and compare it with a normal control group...
  65. Liu J, Dai Y, Li X, Cao K, Xie D, Tong Z, et al. Solute carrier family 12 member 5 promotes tumor invasion/metastasis of bladder urothelial carcinoma by enhancing NF-κB/MMP-7 signaling pathway. Cell Death Dis. 2017;8:e2691 pubmed publisher
    b>Solute carrier family 12 member 5 (SLC12A5), an integral membrane KCl cotransporter, which maintains chloride homeostasis in neurons, is aberrantly expressed and involved in the tumorigenesis of certain cancers...
  66. Tang B. K+-Cl- co-transporter 2 (KCC2) - a membrane trafficking perspective. Mol Membr Biol. 2017;:1-11 pubmed publisher
    K+-Cl- co-transporter 2 (KCC2/SLC12A5) is a neuronal specific cation chloride co-transporter which is active under isotonic conditions, and thus a key regulator of intracellular Cl- levels...
  67. 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 ..
  68. 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...
  69. Lee H, Walker J, Williams J, Goodier R, Payne J, Moss S. Direct protein kinase C-dependent phosphorylation regulates the cell surface stability and activity of the potassium chloride cotransporter KCC2. J Biol Chem. 2007;282:29777-84 pubmed
    The potassium chloride cotransporter KCC2 plays a major role in the maintenance of transmembrane chloride potential in mature neurons; thus KCC2 activity is critical for hyperpolarizing membrane currents generated upon the activation of ..
  70. Chen M, Wang J, Jiang J, Zheng X, Justice N, Wang K, et al. APP modulates KCC2 expression and function in hippocampal GABAergic inhibition. elife. 2017;6: pubmed publisher
    ..biochemical, moleculobiological, and pharmacological analysis, here we show that APP can physically interact with KCC2, a neuron-specific K+-Cl- cotransporter that is essential for Cl- homeostasis and ..
  71. Doyon N, Ferrini F, Gagnon M, De Koninck Y. Treating pathological pain: is KCC2 the key to the gate?. Expert Rev Neurother. 2013;13:469-71 pubmed publisher
  72. Mercado A, Broumand V, Zandi Nejad K, Enck A, Mount D. A C-terminal domain in KCC2 confers constitutive K+-Cl- cotransport. J Biol Chem. 2006;281:1016-26 pubmed
    The neuron-specific K(+)-Cl(-) cotransporter KCC2 plays a crucial role in determining intracellular chloride activity and thus the neuronal response to gamma-aminobutyric acid and glycine...
  73. 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...
  74. 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 ..
  75. Yang C, Liu S, Wang H, Li Y, Guo D, Wang X, et al. Neuroprotection by Propofol Post-Conditioning: Focus on PKM?/KCC2 Pathway Activity. Cell Mol Neurobiol. 2018;38:691-701 pubmed publisher
    ..provided neuroprotective functions through upregulating the expression of potassium chloride cotransporter 2 (KCC2) in gamma-aminobutyric acid (GABA) interneurons...
  76. Vaaga C, Miller K, Bodor A, Perkel D. Expression of the potassium-chloride co-transporter, KCC2, within the avian song system. J Comp Neurol. 2017;: pubmed publisher
    ..potential is determined, in part, by the expression level of a neuron-specific potassium-chloride cotransporter, KCC2, which is developmentally upregulated in mammals...
  77. Wei W, Akerman C, Newey S, Pan J, Clinch N, Jacob Y, et al. The potassium-chloride cotransporter 2 promotes cervical cancer cell migration and invasion by an ion transport-independent mechanism. J Physiol. 2011;589:5349-59 pubmed publisher
    ..Unlike other ubiquitously expressed KCC isoforms, expression of KCC2 is widely considered to be restricted to neurons, where it is responsible for maintaining a low intracellular ..
  78. Kahle K, Merner N, Friedel P, Silayeva L, Liang B, Khanna A, et al. Genetically encoded impairment of neuronal KCC2 cotransporter function in human idiopathic generalized epilepsy. EMBO Rep. 2014;15:766-74 pubmed publisher
    The KCC2 cotransporter establishes the low neuronal Cl(-) levels required for GABAA and glycine (Gly) receptor-mediated inhibition, and KCC2 deficiency in model organisms results in network hyperexcitability...
  79. Amin H, Marinaro F, De Pietri Tonelli D, Berdondini L. Developmental excitatory-to-inhibitory GABA-polarity switch is disrupted in 22q11.2 deletion syndrome: a potential target for clinical therapeutics. Sci Rep. 2017;7:15752 pubmed publisher
    ..found embryonic-premature alterations in the neuronal chloride cotransporters indicated by dysregulated NKCC1 and KCC2 protein expression levels...
  80. Di Cristo G, Awad P, Hamidi S, Avoli M. KCC2, epileptiform synchronization, and epileptic disorders. Prog Neurobiol. 2018;162:1-16 pubmed publisher
    The K+-Cl- co-transporter KCC2 is a neuron-specific, Cl- extruder that uses K+ gradient for maintaining low intracellular [Cl-]...
  81. 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
    ..KCC2 (gene symbol SLC12A5) is expressed exclusively in neurons within the central nervous system and abnormalities in its expression have ..
  82. Tang X, Kim J, Zhou L, Wengert E, Zhang L, Wu Z, et al. KCC2 rescues functional deficits in human neurons derived from patients with Rett syndrome. Proc Natl Acad Sci U S A. 2016;113:751-6 pubmed publisher
    ..Here we demonstrate that neuron-specific K(+)-Cl(-) cotransporter2 (KCC2) is a critical downstream gene target of MeCP2...
  83. Sanchez Brualla I, Boulenguez P, Brocard C, Liabeuf S, Viallat Lieutaud A, Navarro X, et al. Activation of 5-HT2A Receptors Restores KCC2 Function and Reduces Neuropathic Pain after Spinal Cord Injury. Neuroscience. 2018;387:48-57 pubmed publisher
    Downregulation of the potassium chloride cotransporter type 2 (KCC2) after a spinal cord injury (SCI) disinhibits motoneurons and dorsal horn interneurons causing spasticity and neuropathic pain, respectively...
  84. Lee H, Chen C, Liu Y, Aizenman E, Kandler K. KCC2 expression in immature rat cortical neurons is sufficient to switch the polarity of GABA responses. Eur J Neurosci. 2005;21:2593-9 pubmed
    ..In order to address this question, we used a gain-of-function approach by over-expressing human KCC2 (hKCC2) in immature cortical neurons, before endogenous up-regulation of KCC2...
  85. Llano O, Smirnov S, Soni S, Golubtsov A, Guillemin I, Hotulainen P, et al. KCC2 regulates actin dynamics in dendritic spines via interaction with β-PIX. J Cell Biol. 2015;209:671-86 pubmed publisher
    Chloride extrusion in mature neurons is largely mediated by the neuron-specific potassium-chloride cotransporter KCC2. In addition, independently of its chloride transport function, KCC2 regulates the development and morphology of ..
  86. 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...
  87. 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...
  88. Markkanen M, Ludwig A, Khirug S, Pryazhnikov E, Soni S, Khiroug L, et al. Implications of the N-terminal heterogeneity for the neuronal K-Cl cotransporter KCC2 function. Brain Res. 2017;1675:87-101 pubmed publisher
    The neuron-specific K-Cl cotransporter KCC2 maintains the low intracellular chloride concentration required for the fast hyperpolarizing responses of the inhibitory neurotransmitters ?-aminobutyric acid (GABA) and glycine...
  89. Mahadevan V, Khademullah C, Dargaei Z, Chevrier J, Uvarov P, Kwan J, et al. Native KCC2 interactome reveals PACSIN1 as a critical regulator of synaptic inhibition. elife. 2017;6: pubmed publisher
    b>KCC2 is a neuron-specific K+-Cl- cotransporter essential for establishing the Cl- gradient required for hyperpolarizing inhibition in the central nervous system (CNS)...
  90. Rivera C, Voipio J, Kaila K. Two developmental switches in GABAergic signalling: the K+-Cl- cotransporter KCC2 and carbonic anhydrase CAVII. J Physiol. 2005;562:27-36 pubmed
    ..is influenced by the neuronal expression of two key molecules: the chloride-extruding K(+)-Cl(-) cotransporter KCC2, and the cytosolic carbonic anhydrase (CA) isoform CAVII...
  91. Castro A, Li Y, Raver C, Chandra R, Masri R, Lobo M, et al. Neuropathic pain after chronic nerve constriction may not correlate with chloride dysregulation in mouse trigeminal nucleus caudalis neurons. Pain. 2017;158:1366-1372 pubmed publisher
    ..These changes correlate with a decrease in the expression of the potassium chloride transporter, KCC2, and with increases in neuronal excitability...
  92. Moore Y, Kelley M, Brandon N, Deeb T, Moss S. Seizing Control of KCC2: A New Therapeutic Target for Epilepsy. Trends Neurosci. 2017;40:555-571 pubmed publisher
    ..is dependent on chloride extrusion by the neuron-specific type 2K+-Cl- cotransporter (KCC2)...