KCC2 activity is critical in limiting the onset and severity of status epilepticus

Proceedings of the National Academy of Sciences of the United States of America

Volumn 112, Issue 11, 2015, Pages 3523-3528

  Silayeva, Liliya ^a,b   Deeb, Tarek Z ^a,b   Hines, Rochelle M ^b   Kelley, Matt R ^b   Munoz, Michaelanne B ^a   Lee, Henry H C ^c   Brandon, Nicholas J ^a   Dunlop, John ^a   Maguire, Jaime ^b   Davies, Paul A ^b   Moss, Stephen J ^a,b,d  

^a ASTRAZENECA   (United Kingdom)

^b TUFTS UNIVERSITY SCHOOL OF MEDICINE   (United States)

^c BOSTON CHILDREN S HOSPITAL   (United States)

^d UNIVERSITY COLLEGE LONDON   (United Kingdom)

Author keywords

Chloride; Epilepsy; Kainate; KCC2; Phosphorylation

Indexed keywords

ALANINE; GLUTAMIC ACID; KAINIC ACID; POTASSIUM CHLORIDE COTRANSPORTER 2; PROTEIN; S940 PROTEIN; UNCLASSIFIED DRUG; 4 AMINOBUTYRIC ACID; CHLORIDE; COTRANSPORTER; GLUTAMIC ACID DERIVATIVE; MUTANT PROTEIN; PHOSPHOPROTEIN PHOSPHATASE 1; PHOSPHOSERINE; POTASSIUM-CHLORIDE SYMPORTERS;

ADULT; ANIMAL CELL; ANIMAL EXPERIMENT; ANIMAL MODEL; ARTICLE; COMPARATIVE STUDY; CONTROLLED STUDY; DISEASE SEVERITY; EPILEPTIC STATE; EPILEPTOGENESIS; GENE MUTATION; HIPPOCAMPAL NEURONAL CULTURE; HOMOZYGOTE; IN VITRO STUDY; INTERNALIZATION; LETHALITY; MOUSE; NERVE CELL; NONHUMAN; PHENOTYPE; PRIORITY JOURNAL; PROTEIN DEPHOSPHORYLATION; PROTEIN EXPRESSION; PROTEIN PHOSPHORYLATION; WILD TYPE; ANIMAL; ANTAGONISTS AND INHIBITORS; ENDOCYTOSIS; GENE TARGETING; GENETICS; METABOLISM; MOUSE MUTANT; MUTATION; PATHOLOGY; PHOSPHORYLATION;

MUS;

ANIMALS; CHLORIDES; ENDOCYTOSIS; GAMMA-AMINOBUTYRIC ACID; GENE KNOCK-IN TECHNIQUES; GLUTAMATES; MICE; MICE, NEUROLOGIC MUTANTS; MUTANT PROTEINS; MUTATION; PHOSPHORYLATION; PHOSPHOSERINE; PROTEIN PHOSPHATASE 1; STATUS EPILEPTICUS; SYMPORTERS;

EID: 84925275597     PISSN: 00278424     EISSN: 10916490     Source Type: Journal    
DOI: 10.1073/pnas.1415126112     Document Type: Article

References (34)

1. Blaesse P, Airaksinen MS, Rivera C, Kaila K (2009) Cation-chloride cotransporters and neuronal function. Neuron 61(6):820-838.
2. Hübner CA, et al. (2001) Disruption of KCC2 reveals an essential role of K-Cl cotransport already in early synaptic inhibition. Neuron 30(2):515-524.
3. Li H, et al. (2007) KCC2 interacts with the dendritic cytoskeleton to promote spine development. Neuron 56(6):1019-1033.
4. Gauvain G, et al. (2011) The neuronal K-Cl cotransporter KCC2 influences postsynaptic AMPA receptor content and lateral diffusion in dendritic spines. Proc Natl Acad Sci USA 108(37):15474-15479.
5. Mahadevan V, et al. (2014) Kainate receptors coexist in a functional complex with KCC2 and regulate chloride homeostasis in hippocampal neurons. Cell Reports 7(6):1762-1770.
6. Fiumelli H, et al. (2013) An ion transport-independent role for the cation-chloride cotransporter KCC2 in dendritic spinogenesis in vivo. Cereb Cortex 23(2):378-388.
7. Milgram NW, Yearwood T, Khurgel M, Ivy GO, Racine R (1991) Changes in inhibitory processes in the hippocampus following recurrent seizures induced by systemic administration of kainic acid. Brain Res 551(1-2):236-246.
8. Goodkin HP, Kapur J (2009) The impact of diazepam's discovery on the treatment and understanding of status epilepticus. Epilepsia 50(9):2011-2018.
9. Deeb TZ, Maguire J, Moss SJ (2012) Possible alterations in GABAA receptor signaling that underlie benzodiazepine-resistant seizures. Epilepsia 53(Suppl 9):79-88.
10. Medina I, et al. (2014) Current view on the functional regulation of the neuronal K(+)-Cl(-) cotransporter KCC2. Front Cell Neurosci 8:27.
11. Pathak HR, et al. (2007) Disrupted dentate granule cell chloride regulation enhances synaptic excitability during development of temporal lobe epilepsy. J Neurosci 27(51): 14012-14022.
12. Lee HH, Jurd R, Moss SJ (2010) Tyrosine phosphorylation regulates the membrane trafficking of the potassium chloride co-transporter KCC2. Mol Cell Neurosci 45(2):173-179.
13. Barmashenko G, Hefft S, Aertsen A, Kirschstein T, Köhling R (2011) Positive shifts of the GABAA receptor reversal potential due to altered chloride homeostasis is widespread after status epilepticus. Epilepsia 52(9):1570-1578.
14. Lee HH, et al. (2007) Direct protein kinase C-dependent phosphorylation regulates the cell surface stability and activity of the potassium chloride cotransporter KCC2.J Biol Chem 282(41):29777-29784.
15. Lee HH, Deeb TZ, Walker JA, Davies PA, Moss SJ (2011) NMDA receptor activity downregulates KCC2 resulting in depolarizing GABAA receptor-mediated currents. Nat Neurosci 14(6):736-743.
16. Racine RJ (1972) Modification of seizure activity by electrical stimulation. II. Motor seizure. Electroencephalogr Clin Neurophysiol 32(3):281-294.
17. Gulyás AI, Sík A, Payne JA, Kaila K, Freund TF (2001) The KCl cotransporter, KCC2, is highly expressed in the vicinity of excitatory synapses in the rat hippocampus. Eur J Neurosci 13(12):2205-2217.
18. Dreier JP, Heinemann U (1990) Late low magnesium-induced epileptiform activity in rat entorhinal cortex slices becomes insensitive to the anticonvulsant valproic acid. Neurosci Lett 119(1):68-70.
19. Farrant M, Kaila K (2007) The cellular, molecular and ionic basis of GABA(A) receptor signalling. Prog Brain Res 160:59-87.
20. Deeb TZ, Nakamura Y, Frost GD, Davies PA, Moss SJ (2013) Disrupted Cl(-) homeostasis contributes to reductions in the inhibitory efficacy of diazepam during hyperexcited states. Eur J Neurosci 38(3):2453-2467.
21. Delpire E, et al. (2009) Small-molecule screen identifies inhibitors of the neuronal K-Cl cotransporter KCC2. Proc Natl Acad Sci USA 106(13):5383-5388.
22. Naylor DE, Liu H, Wasterlain CG (2005) Trafficking of GABA(A) receptors, loss of inhibition, and a mechanism for pharmacoresistance in status epilepticus. J Neurosci 25(34):7724-7733.
23. Goodkin HP, Joshi S, Mtchedlishvili Z, Brar J, Kapur J (2008) Subunit-specific trafficking of GABA(A) receptors during status epilepticus. J Neurosci 28(10):2527-2538.
24. Terunuma M, et al. (2008) Deficits in phosphorylation of GABA(A) receptors by intimately associated protein kinase C activity underlie compromised synaptic inhibition during status epilepticus. J Neurosci 28(2):376-384.
25. Huberfeld G, et al. (2007) Perturbed chloride homeostasis and GABAergic signaling in human temporal lobe epilepsy. J Neurosci 27(37):9866-9873.
26. Dreier JP, Heinemann U (1991) Regional and time dependent variations of low Mg2+ induced epileptiform activity in rat temporal cortex slices. Exp Brain Res 87(3):581-596.
27. During MJ, Spencer DD (1993) Extracellular hippocampal glutamate and spontaneous seizure in the conscious human brain. Lancet 341(8861):1607-1610.
28. Rinehart J, et al. (2009) Sites of regulated phosphorylation that control K-Cl cotransporter activity. Cell 138(3):525-536.
29. de Los Heros P, et al. (2014) The WNK-regulated SPAK/OSR1 kinases directly phosphorylate and inhibit the K+-Cl-co-transporters. Biochem J 458(3):559-573.
30. Jennings ML, Schulz RK (1991) Okadaic acid inhibition of KCl cotransport. Evidence that protein dephosphorylation is necessary for activation of transport by either cell swelling or N-ethylmaleimide. J Gen Physiol 97(4):799-817.
31. Puskarjov M, et al. (2014) A variant of KCC2 from patients with febrile seizures impairs neuronal Cl-extrusion and dendritic spine formation. EMBO Rep 15(6):723-729.
32. Kahle KT, et al. (2014) Genetically encoded impairment of neuronal KCC2 cotransporter function in human idiopathic generalized epilepsy. EMBO Rep 15(7): 766-774.
33. Glykys J, et al. (2014) Local impermeant anions establish the neuronal chloride concentration. Science 343(6171):670-675.
34. Tretter V, et al. (2009) Deficits in spatial memory correlate with modified gammaaminobutyric acid type A receptor tyrosine phosphorylation in the hippocampus. Proc Natl Acad Sci USA 106(47):20039-20044.