The role of glial-specific Kir4.1 in normal and pathological states of the CNS

Acta Neuropathologica

Volumn 132, Issue 1, 2016, Pages

  Nwaobi, Sinifunanya E ^a   Cuddapah, Vishnu A ^a   Patterson, Kelsey C ^a   Randolph, Anita C ^a   Olsen, Michelle L ^a  

^a UNIVERSITY OF ALABAMA AT BIRMINGHAM   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

INWARDLY RECTIFYING POTASSIUM CHANNEL; INWARDLY RECTIFYING POTASSIUM CHANNEL SUBUNIT KIR4.1; POTASSIUM; POTASSIUM CHANNEL BLOCKING AGENT; UNCLASSIFIED DRUG; KCNJ10 (CHANNEL);

ALEXANDER DISEASE; ALZHEIMER DISEASE; AMYOTROPHIC LATERAL SCLEROSIS; ASTROCYTE; AUTISM; AUTOIMMUNE DISEASE; BRAIN ISCHEMIA; CELL CYCLE; CELL MATURATION; CENTRAL NERVOUS SYSTEM DISEASE; COGNITIVE DEFECT; DEVELOPMENTAL DISORDER; DRUG TARGETING; ENCEPHALITIS; EPILEPSY; GENE; GENE EXPRESSION PROFILING; GENE LOSS; GENE MUTATION; GENETIC MANIPULATION; GLIA CELL; GLIOSIS; HOMEOSTASIS; HUMAN; HUNTINGTON CHOREA; HYPERPOLARIZATION; KCNJ10 GENE; MEMBRANE STEADY POTENTIAL; MOLECULAR PATHOLOGY; NEUROPATHOLOGY; NONHUMAN; PAIN; POTASSIUM CONDUCTANCE; POTASSIUM HOMEOSTASIS; PRIORITY JOURNAL; PROTEIN EXPRESSION; PROTEIN LOCALIZATION; RETT SYNDROME; REVIEW; SEIZURE; SESAME EAST SYNDROME; SYNDROME; TRAUMATIC BRAIN INJURY; ANIMAL; CENTRAL NERVOUS SYSTEM; METABOLISM;

ANIMALS; CENTRAL NERVOUS SYSTEM; CENTRAL NERVOUS SYSTEM DISEASES; HUMANS; POTASSIUM CHANNELS, INWARDLY RECTIFYING;

EID: 84960172417     PISSN: 00016322     EISSN: 14320533     Source Type: Journal    
DOI: 10.1007/s00401-016-1553-1     Document Type: Review

References (129)

1. Anderova M, Antonova T, Petrik D, Neprasova H, Chvatal A, Sykova E (2004) Voltage-dependent potassium currents in hypertrophied rat astrocytes after a cortical stab wound. Glia 48:311–326
2. Anderson CM, Swanson RA (2000) Astrocyte glutamate transport: review of properties, regulation, and physiological functions. Glia 32:1–14
3. Arzberger T, Krampfl K, Leimgruber S, Weindl A (1997) Changes of NMDA receptor subunit (NR1, NR2B) and glutamate transporter (GLT1) mRNA expression in Huntington’s disease—an in situ hybridization study. J Neuropathol Exp Neurol 56:440–454
4. Barbour B, Brew H, Attwell D (1988) Electrogenic glutamate uptake in glial cells is activated by intracellular potassium. Nature 335:433–435
5. Bataveljic D, Nikolic L, Milosevic M, Todorovic N, Andjus PR (2012) Changes in the astrocytic aquaporin-4 and inwardly rectifying potassium channel expression in the brain of the amyotrophic lateral sclerosis SOD1(G93A) rat model. Glia 60:1991–2003
6. Bay V, Butt AM (2012) Relationship between glial potassium regulation and axon excitability: a role for glial Kir4.1 channels. Glia 60:651–660
7. Bockenhauer D et al (2009) Epilepsy, ataxia, sensorineural deafness, tubulopathy, and KCNJ10 mutations. N Engl J Med 360:1960–1970
8. Bordey A, Lyons SA, Hablitz JJ, Sontheimer H (2001) Electrophysiological characteristics of reactive astrocytes in experimental cortical dysplasia. J Neurophysiol 85:1719–1731
9. Bordey A, Sontheimer H (1997) Postnatal development of ionic currents in rat hippocampal astrocytes in situ. J Neurophysiol 78:461–477
10. Bordey A, Sontheimer H (1998) Properties of human glial cells associated with epileptic seizure foci. Epilepsy Res 32:286–303
11. Brenner M, Johnson AB, Boespflug-Tanguy O, Rodriguez D, Goldman JE, Messing A (2001) Mutations in GFAP, encoding glial fibrillary acidic protein, are associated with Alexander disease. Nat Genet 27:117–120
12. Brickshawana A, Hinson SR, Romero MF, Lucchinetti CF, Guo Y, Buttmann M, McKeon A, Pittock SJ, Chang MH, Chen AP, Kryzer TJ, Fryer JP, Jenkins SM, Cabre P, Lennon VA (2014) Investigation of the KIR4.1 potassium channel as a putative antigen in patients with multiple sclerosis: a comparative study. Lancet Neurol 13:795–806
13. Buono RJ, Lohoff FW, Sander T, Sperling MR, O’Connor MJ, Dlugos DJ, Ryan SG, Golden GT, Zhao H, Scattergood TM, Berrettini WH, Ferraro TN (2004) Association between variation in the human KCNJ10 potassium ion channel gene and seizure susceptibility. Epilepsy Res 58:175–183
14. Chen Y, Swanson RA (2003) Astrocytes and brain injury. J Cereb Blood Flow Metab 23:137–149
15. Chever O, Djukic B, McCarthy KD, Amzica F (2010) Implication of Kir4.1 channel in excess potassium clearance: an in vivo study on anesthetized glial-conditional Kir4.1 knock-out mice. J Neurosci 30:15769–15777
16. Cone CD Jr (1970) Variation of the transmembrane potential level as a basic mechanism of mitosis control. Oncology 24:438–470
17. Connors NC, Kofuji P (2006) Potassium channel Kir4.1 macromolecular complex in retinal glial cells. Glia 53:124–131
18. D’Ambrosio R, Gordon DS, Winn HR (2002) Differential role of KIR channel and Na(+)/K(+)-pump in the regulation of extracellular K(+) in rat hippocampus. J Neurophysiol 87:87–102
19. Dai AI, Akcali A, Koska S, Oztuzcu S, Cengiz B, Demiryurek AT (2015) Contribution of KCNJ10 gene polymorphisms in childhood epilepsy. J Child Neurol 30:296–300
20. Dibaj P, Kaiser M, Hirrlinger J, Kirchhoff F, Neusch C (2007) Kir4.1 channels regulate swelling of astroglial processes in experimental spinal cord edema. J Neurochem 103:2620–2628
21. Djukic B, Casper KB, Philpot BD, Chin LS, McCarthy KD (2007) Conditional knock-out of Kir4.1 leads to glial membrane depolarization, inhibition of potassium and glutamate uptake, and enhanced short-term synaptic potentiation. J Neurosci 27:11354–11365
22. Erlichman JS, Leiter JC, Gourine AV (2010) ATP, glia and central respiratory control. Respir Physiol Neurobiol 173:305–311
23. Estrada-Sanchez AM, Montiel T, Segovia J, Massieu L (2009) Glutamate toxicity in the striatum of the R6/2 Huntington’s disease transgenic mice is age-dependent and correlates with decreased levels of glutamate transporters. Neurobiol Dis 34:78–86
24. Estrada-Sanchez AM, Rebec GV (2012) Corticostriatal dysfunction and glutamate transporter 1 (GLT1) in Huntington’s disease: interactions between neurons and astrocytes. Basal Ganglia 2:57–66
25. Ferraro TN, Golden GT, Smith GG, Martin JF, Lohoff FW, Gieringer TA, Zamboni D, Schwebel CL, Press DM, Kratzer SO, Zhao H, Berrettini WH, Buono RJ (2004) Fine mapping of a seizure susceptibility locus on mouse Chromosome 1: nomination of Kcnj10 as a causative gene. Mamm Genome 15:239–251
26. Gao F, Li F, Miao Y, Dong LD, Zhang SH, Wu J, Sun XH, Wang Z (2015) Group I metabotropic glutamate receptor agonist DHPG modulates Kir4.1 protein and mRNA in cultured rat retinal Muller cells. Neurosci Lett 588:12–17
27. Gilliam D, O’Brien DP, Coates JR, Johnson GS, Johnson GC, Mhlanga-Mutangadura T, Hansen L, Taylor JF, Schnabel RD (2014) A homozygous KCNJ10 mutation in Jack Russell terriers and related breeds with spinocerebellar ataxia with myokymia, seizures, or both. J Vet Intern Med 28(3):871–877
28. Gourine AV, Kasymov V, Marina N, Tang F, Figueiredo MF, Lane S, Teschemacher AG, Spyer KM, Deisseroth K, Kasparov S (2010) Astrocytes control breathing through pH-dependent release of ATP. Science 329:571–575
29. Hablitz JJ, Heinemann U (1989) Alterations in the microenvironment during spreading depression associated with epileptiform activity in the immature neocortex. Brain Res Dev Brain Res 46:243–252
30. Haj-Yasein NN, Jensen V, Vindedal GF, Gundersen GA, Klungland A, Ottersen OP, Hvalby O, Nagelhus EA (2011) Evidence that compromised K+ spatial buffering contributes to the epileptogenic effect of mutations in the human kir4.1 gene (KCNJ10). Glia 59:1635–1642
31. Hibino H, Fujita A, Iwai K, Yamada M, Kurachi Y (2004) Differential assembly of inwardly rectifying K+ channel subunits, Kir4.1 and Kir5.1, in brain astrocytes. J Biol Chem 279:44065–44073
32. Hibino H, Inanobe A, Furutani K, Murakami S, Findlay I, Kurachi Y (2010) Inwardly rectifying potassium channels: their structure, function, and physiological roles. Physiol Rev 90:291–366
33. Hibino H, Kurachi Y (2007) Distinct detergent-resistant membrane microdomains (lipid rafts) respectively harvest K(+) and water transport systems in brain astroglia. Eur J Neurosci 26:2539–2555
34. Higashi K, Fujita A, Inanobe A, Tanemoto M, Doi K, Kubo T, Kurachi Y (2001) An inwardly rectifying K(+) channel, Kir4.1, expressed in astrocytes surrounds synapses and blood vessels in brain. Am J Physiol Cell Physiol 281:C922–C931
35. Higashimori H, Sontheimer H (2007) Role of Kir4.1 channels in growth control of glia. Glia 55:1668–1679
36. Hinterkeuser S, Schroder W, Hager G, Seifert G, Blumcke I, Elger CE, Schramm J, Steinhauser C (2000) Astrocytes in the hippocampus of patients with temporal lobe epilepsy display changes in potassium conductances. Eur J Neurosci 12:2087–2096
37. Hirrlinger PG, Pannicke T, Winkler U, Claudepierre T, Varshney S, Schulze C, Reichenbach A, Brunken WJ, Hirrlinger J (2011) Genetic deletion of laminin isoforms beta2 and gamma3 induces a reduction in Kir4.1 and aquaporin-4 expression and function in the retina. PLoS ONE 6:e16106
38. Huang Y, Mucke L (2012) Alzheimer mechanisms and therapeutic strategies. Cell 148:1204–1222
39. Inyushin M, Kucheryavykh LY, Kucheryavykh YV, Nichols CG, Buono RJ, Ferraro TN, Skatchkov SN, Eaton MJ (2010) Potassium channel activity and glutamate uptake are impaired in astrocytes of seizure-susceptible DBA/2 mice. Epilepsia 51:1707–1713
40. Ishii M, Horio Y, Tada Y, Hibino H, Inanobe A, Ito M, Yamada M, Gotow T, Uchiyama Y, Kurachi Y (1997) Expression and clustered distribution of an inwardly rectifying potassium channel, KAB-2/Kir4.1, on mammalian retinal Muller cell membrane: their regulation by insulin and laminin signals. J Neurosci 17:7725–7735
41. Jansen LA, Uhlmann EJ, Crino PB, Gutmann DH, Wong M (2005) Epileptogenesis and reduced inward rectifier potassium current in tuberous sclerosis complex-1-deficient astrocytes. Epilepsia 46:1871–1880
42. Ji M, Miao Y, Dong LD, Chen J, Mo XF, Jiang SX, Sun XH, Yang XL, Wang Z (2012) Group I mGluR-mediated inhibition of Kir channels contributes to retinal Muller cell gliosis in a rat chronic ocular hypertension model. J Neurosci 32:12744–12755
43. Kaiser M, Maletzki I, Hulsmann S, Holtmann B, Schulz-Schaeffer W, Kirchhoff F, Bahr M, Neusch C (2006) Progressive loss of a glial potassium channel (KCNJ10) in the spinal cord of the SOD1 (G93A) transgenic mouse model of amyotrophic lateral sclerosis. J Neurochem 99:900–912
44. Kalsi AS, Greenwood K, Wilkin G, Butt AM (2004) Kir4.1 expression by astrocytes and oligodendrocytes in CNS white matter: a developmental study in the rat optic nerve. J Anat 204:475–485
45. Katayama Y, Becker DP, Tamura T, Hovda DA (1990) Massive increases in extracellular potassium and the indiscriminate release of glutamate following concussive brain injury. J Neurosurg 73:889–900
46. Kilpinen H, Ylisaukko-oja T, Rehnström K, Gaál E, Turunen JA, Kempas E, von Wendt L, Varilo T, Peltonen L (2009) Linkage and linkage disequilibrium scan for autism loci in an extended pedigree from Finland. Hum Mol Genet 18:2912–2921
47. Kofuji P, Biedermann B, Siddharthan V, Raap M, Iandiev I, Milenkovic I, Thomzig A, Veh RW, Bringmann A, Reichenbach A (2002) Kir potassium channel subunit expression in retinal glial cells: implications for spatial potassium buffering. Glia 39:292–303
48. Kofuji P, Connors NC (2003) Molecular substrates of potassium spatial buffering in glial cells. Mol Neurobiol 28:195–208
49. Kofuji P, Newman EA (2004) Potassium buffering in the central nervous system. Neuroscience 129:1043–1054
50. Kofuji P, Ceelen P, Zahs KR, Surbeck LW, Lester HA, Newman EA (2000) Genetic inactivation of an inwardly rectifying potassium channel (Kir4.1 subunit) in mice: phenotypic impact in retina. J Neurosci 20:5733–5740
51. Koller H, Schroeter M, Jander S, Stoll G, Siebler M (2000) Time course of inwardly rectifying K(+) current reduction in glial cells surrounding ischemic brain lesions. Brain Res 872:194–198
52. Kucheryavykh YV, Kucheryavykh LY, Nichols CG, Maldonado HM, Baksi K, Reichenbach A, Skatchkov SN, Eaton MJ (2007) Downregulation of Kir4.1 inward rectifying potassium channel subunits by RNAi impairs potassium transfer and glutamate uptake by cultured cortical astrocytes. Glia 55:274–281
53. Kuffler SW (1967) The Ferrier lecture: neuroglial cells: physiological properties and a potassium mediated effect of neuronal activity on the glial membrane potential. Proc R Soc Lond B Biol Sci 168:1–21
54. Larsen BR, Assentoft M, Cotrina ML, Hua SZ, Nedergaard M, Kaila K, Voipio J, MacAulay N (2014) Contributions of the Na(+)/K(+)-ATPase, NKCC1, and Kir4.1 to hippocampal K(+) clearance and volume responses. Glia 62:608–622
55. Larsen BR, MacAulay N (2014) Kir4.1-mediated spatial buffering of K: experimental challenges in determination of its temporal and quantitative contribution to K clearance in the brain. Channels (Austin) 8(6):544–550
56. Lenzen KP, Heils A, Lorenz S, Hempelmann A, Hofels S, Lohoff FW, Schmitz B, Sander T (2005) Supportive evidence for an allelic association of the human KCNJ10 potassium channel gene with idiopathic generalized epilepsy. Epilepsy Res 63:113–118
57. Li L, Head V, Timpe LC (2001) Identification of an inward rectifier potassium channel gene expressed in mouse cortical astrocytes. Glia 33:57–71
58. Lioy DT, Garg SK, Monaghan CE, Raber J, Foust KD, Kaspar BK, Hirrlinger PG, Kirchhoff F, Bissonnette JM, Ballas N, Mandel G (2011) A role for glia in the progression of Rett’s syndrome. Nature 475:497–500
59. Ma B, Buckalew R, Du Y, Kiyoshi CM, Alford CC, Wang W, McTigue DM, Enyeart JJ, Terman D, Zhou M (2015) Gap junction coupling confers isopotentiality on astrocyte syncytium. Glia 64(2):214–226
60. Ma B, Xu G, Wang W, Enyeart JJ, Zhou M (2014) Dual patch voltage clamp study of low membrane resistance astrocytes in situ. Mol Brain 7:18
61. MacFarlane SN, Sontheimer H (1997) Electrophysiological changes that accompany reactive gliosis in vitro. J Neurosci 17:7316–7329
62. MacFarlane SN, Sontheimer H (2000) Changes in ion channel expression accompany cell cycle progression of spinal cord astrocytes. Glia 30:39–48
63. Mahmood F, Mozere M, Zdebik AA, Stanescu HC, Tobin J, Beales PL, Kleta R, Bockenhauer D, Russell C (2013) Generation and validation of a zebrafish model of EAST (epilepsy, ataxia, sensorineural deafness and tubulopathy) syndrome. Dis Model Mech 6:652–660
64. Maldonado PP, Velez-Fort M, Levavasseur F, Angulo MC (2013) Oligodendrocyte precursor cells are accurate sensors of local K+ in mature gray matter. J Neurosci 33:2432–2442
65. Marcus DC, Wu T, Wangemann P, Kofuji P (2002) KCNJ10 (Kir4.1) potassium channel knockout abolishes endocochlear potential. Am J Physiol Cell Physiol 282:C403–C407
66. McTigue DM, Wei P, Stokes BT (2001) Proliferation of NG2-positive cells and altered oligodendrocyte numbers in the contused rat spinal cord. J Neurosci 21:3392–3400
67. Meeks JP, Mennerick S (2007) Astrocyte membrane responses and potassium accumulation during neuronal activity. Hippocampus 17:1100–1108
68. Messing A, Head MW, Galles K, Galbreath EJ, Goldman JE, Brenner M (1998) Fatal encephalopathy with astrocyte inclusions in GFAP transgenic mice. Am J Pathol 152:391–398
69. Miller BR, Dorner JL, Shou M, Sari Y, Barton SJ, Sengelaub DR, Kennedy RT, Rebec GV (2008) Up-regulation of GLT1 expression increases glutamate uptake and attenuates the Huntington’s disease phenotype in the R6/2 mouse. Neuroscience 153:329–337
70. Minkel HR, Anwer TZ, Arps KM, Brenner M, Olsen ML (2015) Elevated GFAP induces astrocyte dysfunction in caudal brain regions: A potential mechanism for hindbrain involved symptoms in type II Alexander disease. Glia 63(12):2285–2297
71. Moalem G, Tracey DJ (2006) Immune and inflammatory mechanisms in neuropathic pain. Brain Res Rev 51:240–264
72. Moody WJ, Futamachi KJ, Prince DA (1974) Extracellular potassium activity during epileptogenesis. Exp Neurol 42:248–263
73. Nagelhus EA, Mathiisen TM, Ottersen OP (2004) Aquaporin-4 in the central nervous system: cellular and subcellular distribution and coexpression with KIR4.1. Neuroscience 129:905–913
74. Nerrant E, Salsac C, Charif M, Ayrignac X, Carra-Dalliere C, Castelnovo G, Goulabchand R, Tisseyre J, Raoul C, Eliaou JF, Labauge P, Vincent T (2014) Lack of confirmation of anti-inward rectifying potassium channel 4.1 antibodies as reliable markers of multiple sclerosis. Mult Scler 20:1699–1703
75. Neusch C, Papadopoulos N, Muller M, Maletzki I, Winter SM, Hirrlinger J, Handschuh M, Bahr M, Richter DW, Kirchhoff F, Hulsmann S (2006) Lack of the Kir4.1 channel subunit abolishes K+ buffering properties of astrocytes in the ventral respiratory group: impact on extracellular K+ regulation. J Neurophysiol 95:1843–1852
76. Neusch C, Rozengurt N, Jacobs RE, Lester HA, Kofuji P (2001) Kir4.1 potassium channel subunit is crucial for oligodendrocyte development and in vivo myelination. J Neurosci 21:5429–5438
77. Newman EA (1985) Voltage-dependent calcium and potassium channels in retinal glial cells. Nature 317:809–811
78. Noel G, Belda M, Guadagno E, Micoud J, Klocker N, Moukhles H (2005) Dystroglycan and Kir4.1 coclustering in retinal Muller glia is regulated by laminin-1 and requires the PDZ-ligand domain of Kir4.1. J Neurochem 94:691–702
79. Nwaobi SE, Lin E, Peramsetty SR, Olsen ML (2014) DNA methylation functions as a critical regulator of Kir4.1 expression during CNS development. Glia 62:411–427
80. Ohno Y, Hibino H, Lossin C, Inanobe A, Kurachi Y (2007) Inhibition of astroglial Kir4.1 channels by selective serotonin reuptake inhibitors. Brain Res 1178:44–51
81. Oliver D, Baukrowitz T, Fakler B (2000) Polyamines as gating molecules of inward-rectifier K+ channels. Eur J Biochem 267:5824–5829
82. Olsen M (2012) Examining potassium channel function in astrocytes. Methods Mol Biol 814:265–281
83. Olsen ML, Campbell SL, Sontheimer H (2007) Differential distribution of Kir4.1 in spinal cord astrocytes suggests regional differences in K+ homeostasis. J Neurophysiol 98:786–793
84. Olsen ML, Higashimori H, Campbell SL, Hablitz JJ, Sontheimer H (2006) Functional expression of Kir4.1 channels in spinal cord astrocytes. Glia 53:516–528
85. Olsen ML, Khakh BS, Skatchkov SN, Zhou M, Lee CJ, Rouach N (2015) New insights on astrocyte ion channels: critical for homeostasis and neuron-glia signaling. J Neurosci 35:13827–13835
86. Olsen ML, Sontheimer H (2008) Functional implications for Kir4.1 channels in glial biology: from K+ buffering to cell differentiation. J Neurochem 107:589–601
87. Olsen ML, Campbell SC, McFerrin MB, Floyd CL, Sontheimer H (2010) Spinal cord injury causes a wide-spread, persistent loss of Kir4.1 and glutamate transporter 1: benefit of 17+ ¦-oestradiol treatment. Brain 133:1013–1025
88. Pannicke T, Iandiev I, Uckermann O, Biedermann B, Kutzera F, Wiedemann P, Wolburg H, Reichenbach A, Bringmann A (2004) A potassium channel-linked mechanism of glial cell swelling in the postischemic retina. Mol Cell Neurosci 26:493–502
89. Papadopoulos N, Winter SM, Hartel K, Kaiser M, Neusch C, Hulsmann S (2008) Possible roles of the weakly inward rectifying k+ channel Kir4.1 (KCNJ10) in the pre-Botzinger complex. Adv Exp Med Biol 605:109–113
90. Pareyson D, Fancellu R, Mariotti C, Romano S, Salmaggi A, Carella F, Girotti F, Gattellaro G, Carriero MR, Farina L, Ceccherini I, Savoiardo M (2008) Adult-onset Alexander disease: a series of eleven unrelated cases with review of the literature. Brain 131:2321–2331
91. Pivonkova H, Benesova J, Butenko O, Chvatal A, Anderova M (2010) Impact of global cerebral ischemia on K+ channel expression and membrane properties of glial cells in the rat hippocampus. Neurochem Int 57:783–794
92. Poopalasundaram S, Knott C, Shamotienko OG, Foran PG, Dolly JO, Ghiani CA, Gallo V, Wilkin GP (2000) Glial heterogeneity in expression of the inwardly rectifying K+ channel, Kir4.1, in adult rat CNS. Glia 30:362–372
93. Ransom CB, Sontheimer H, Janigro D (1996) Astrocytic inwardly rectifying potassium currents are dependent on external sodium ions. J Neurophysiol 76:626–630
94. Ransom CB, Ransom BR, Sontheimer H (2000) Activity-dependent extracellular K+ accumulation in rat optic nerve: the role of glial and axonal Na+ pumps. J Physiol 522:427–442
95. Reichold M, Zdebik AA, Lieberer E, Rapedius M, Schmidt K, Bandulik S, Sterner C, Tegtmeier I, Penton D, Baukrowitz T, Hulton SA, Witzgall R, Ben-Zeev B, Howie AJ, Kleta R, Bockenhauer D, Warth R (2010) KCNJ10 gene mutations causing EAST syndrome (epilepsy, ataxia, sensorineural deafness, and tubulopathy) disrupt channel function. Proc Natl Acad Sci USA 107:14490–14495
96. Rosen DR, Siddique T, Patterson D, Figlewicz DA, Sapp P, Hentati A, Donaldson D, Goto J, O’Regan JP, Deng HX (1993) Mutations in Cu/Zn superoxide dismutase gene are associated with familial amyotrophic lateral sclerosis. Nature 362:59–62
97. Rothstein JD, Dykes-Hoberg M, Pardo CA, Bristol LA, Jin L, Kuncl RW, Kanai Y, Hediger MA, Wang Y, Schielke JP, Welty DF (1996) Knockout of glutamate transporters reveals a major role for astroglial transport in excitotoxicity and clearance of glutamate. Neuron 16:675–686
98. Ruppersberg JP (2000) Intracellular regulation of inward rectifier K+ channels. Pflugers Arch 441:1–11
99. Sala-Rabanal M, Kucheryavykh LY, Skatchkov SN, Eaton MJ, Nichols CG (2010) Molecular mechanisms of EAST/SeSAME syndrome mutations in Kir4.1 (KCNJ10). J Biol Chem 285:36040–36048
100. Scarmeas N, Honig LS, Choi H, Cantero J, Brandt J, Blacker D, Albert M, Amatniek JC, Marder K, Bell K, Hauser WA, Stern Y (2009) Seizures in Alzheimer disease: who, when, and how common? Arch Neurol 66:992–997
101. Scholl UI, Choi M, Liu T, Ramaekers VT, Hausler MG, Grimmer J, Tobe SW, Farhi A, Nelson-Williams C, Lifton RP (2009) Seizures, sensorineural deafness, ataxia, mental retardation, and electrolyte imbalance (SeSAME syndrome) caused by mutations in KCNJ10. Proc Natl Acad Sci USA 106:5842–5847
102. Schroder W, Hinterkeuser S, Seifert G, Schramm J, Jabs R, Wilkin GP, Steinhauser C (2000) Functional and molecular properties of human astrocytes in acute hippocampal slices obtained from patients with temporal lobe epilepsy. Epilepsia 41(Suppl 6):S181–S184
103. Seifert G, Huttmann K, Binder DK, Hartmann C, Wyczynski A, Neusch C, Steinhauser C (2009) Analysis of astroglial K+ Channel Expression In The Developing Hippocampus reveals a predominant role of the Kir4.1 subunit. J Neurosci 29:7474–7488
104. Shin JY, Fang ZH, Yu ZX, Wang CE, Li SH, Li XJ (2005) Expression of mutant huntingtin in glial cells contributes to neuronal excitotoxicity. J Cell Biol 171:1001–1012
105. Sibille J, Pannasch U, Rouach N (2014) Astroglial potassium clearance contributes to short-term plasticity of synaptically evoked currents at the tripartite synapse. J Physiol 592:87–102
106. Sicca F, Imbrici P, D’Adamo MC, Moro F, Bonatti F, Brovedani P, Grottesi A, Guerrini R, Masi G, Santorelli FM, Pessia M (2011) Autism with seizures and intellectual disability: possible causative role of gain-of-function of the inwardly-rectifying K+ channel Kir4.1. Neurobiol Dis 43:239–247
107. Sofroniew MV (2014) Astrogliosis. Cold Spring Harb Perspect Biol 7(2):a020420
108. Sontheimer H, Trotter J, Schachner M, Kettenmann H (1989) Channel expression correlates with differentiation stage during the development of oligodendrocytes from their precursor cells in culture. Neuron 2:1135–1145
109. Srivastava R, Aslam M, Kalluri SR, Schirmer L, Buck D, Tackenberg B, Rothhammer V, Chan A, Gold R, Berthele A, Bennett JL, Korn T, Hemmer B (2012) Potassium channel KIR4.1 as an immune target in multiple sclerosis. N Engl J Med 367:115–123
110. Steiner E, Enzmann GU, Lin S, Ghavampour S, Hannocks MJ, Zuber B, Ruegg MA, Sorokin L, Engelhardt B (2012) Loss of astrocyte polarization upon transient focal brain ischemia as a possible mechanism to counteract early edema formation. Glia 60:1646–1659
111. Steinhauser C, Seifert G (2012) Astrocyte dysfunction in epilepsy. In: Noebels JL, Avoli M, Rogawski MA, Olsen RW, Delgado-Escueta AV (eds) Jasper's Basic Mechanisms of the Epilepsies, 4th edn. Bethesda
112. Stewart TH, Eastman CL, Groblewski PA, Fender JS, Verley DR, Cook DG, D’Ambrosio R (2010) Chronic dysfunction of astrocytic inwardly rectifying K+ channels specific to the neocortical epileptic focus after fluid percussion injury in the rat. J Neurophysiol 104:3345–3360
113. Takeda M, Takahashi M, Nasu M, Matsumoto S (2011) Peripheral inflammation suppresses inward rectifying potassium currents of satellite glial cells in the trigeminal ganglia. Pain 152:2147–2156
114. Takumi T, Ishii T, Horio Y, Morishige K, Takahashi N, Yamada M, Yamashita T, Kiyama H, Sohmiya K, Nakanishi S (1995) A novel ATP-dependent inward rectifier potassium channel expressed predominantly in glial cells. J Biol Chem 270:16339–16346
115. Tang X, Hang D, Sand A, Kofuji P (2010) Variable loss of Kir4.1 channel function in SeSAME syndrome mutations. Biochem Biophys Res Commun 399:537–541
116. Tang X, Taniguchi K, Kofuji P (2009) Heterogeneity of Kir4.1 channel expression in glia revealed by mouse transgenesis. Glia 57:1706–1715
117. Thompson DA, Feather S, Stanescu HC, Freudenthal B, Zdebik AA, Warth R, Ognjanovic M, Hulton SA, Wassmer E, van’t Hoff W, Russell-Eggitt I, Dobbie A, Sheridan E, Kleta R, Bockenhauer D (2011) Altered electroretinograms in patients with KCNJ10 mutations and EAST syndrome. J Physiol 589:1681–1689
118. Tong X, Ao Y, Faas GC, Nwaobi SE, Xu J, Haustein MD, Anderson MA, Mody I, Olsen ML, Sofroniew MV, Khakh BS (2014) Astrocyte Kir4.1 ion channel deficits contribute to neuronal dysfunction in Huntington’s disease model mice. Nat Neurosci 17:694–703
119. Ulbricht E, Pannicke T, Hollborn M, Raap M, Goczalik I, Iandiev I, Hartig W, Uhlmann S, Wiedemann P, Reichenbach A, Bringmann A, Francke M (2008) Proliferative gliosis causes mislocation and inactivation of inwardly rectifying K(+) (Kir) channels in rabbit retinal glial cells. Exp Eye Res 86:305–313
120. Vit JP, Ohara PT, Bhargava A, Kelley K, Jasmin L (2008) Silencing the Kir4.1 potassium channel subunit in satellite glial cells of the rat trigeminal ganglion results in pain-like behavior in the absence of nerve injury. J Neurosci 28:4161–4171
121. Vos BP, Strassman AM, Maciewicz RJ (1994) Behavioral evidence of trigeminal neuropathic pain following chronic constriction injury to the rat’s infraorbital nerve. J Neurosci 14:2708–2723
122. Walz W, MacVicar B (1988) Electrophysiological properties of glial cells: comparison of brain slices with primary cultures. Brain Res 443:321–324
123. Wenker IC, Kreneisz O, Nishiyama A, Mulkey DK (2010) Astrocytes in the retrotrapezoid nucleus sense H + by inhibition of a Kir4.1-Kir5.1-like current and may contribute to chemoreception by a purinergic mechanism. J Neurophysiol 104:3042–3052
124. Wilcock DM, Vitek MP, Colton CA (2009) Vascular amyloid alters astrocytic water and potassium channels in mouse models and humans with Alzheimer’s disease. Neuroscience 159:1055–1069
125. Williams DM, Lopes CMB, Rosenhouse-Dantsker A, Connelly HL, Matavel A, Uchi J, McBeath E, Gray DA (2010) Molecular Basis of Decreased Kir4.1 Function in SeSAME/EAST Syndrome. J Am Soc Nephrol 21:2117–2129
126. Yang Z, Xu H, Cui N, Qu Z, Chanchevalap S, Shen W, Jiang C (2000) Biophysical and molecular mechanisms underlying the modulation of heteromeric Kir4.1-Kir5.1 channels by CO2 and pH. J Gen Physiol 116:33–45
127. Zhang Y, Xu G, Ling Q, Da C (2011) Expression of aquaporin 4 and Kir4.1 in diabetic rat retina: treatment with minocycline. J Int Med Res 39:464–479
128. Zhao M, Bousquet E, Valamanesh F, Farman N, Jeanny JC, Jaisser F, Behar-Cohen FF (2011) Differential regulations of AQP4 and Kir4.1 by triamcinolone acetonide and dexamethasone in the healthy and inflamed retina. Invest Ophthalmol Vis Sci 52:6340–6347
129. Zurolo E, de Groot M, Iyer A, Anink J, van Vliet EA, Heimans JJ, Reijneveld JC, Gorter JA, Aronica E (2012) Regulation of Kir4.1 expression in astrocytes and astrocytic tumors: a role for interleukin-1 beta. J Neuroinflammation 9:280