TABLE 10

Kir4.1 channels

Channel name Kir4.1
Description Glial ATP-dependent inward rectifier potassium channel, subfamily J, member 10
Other names Kir1.2,1 KAB-2,2 BIR10,3 BIRK-10, BIRK-1,4 KCNJ13-PEN
Molecular information Human (KCNJ10): 379aa, Locus ID: 3766, GenBank: U52155, NM_002241, PMID: 8995301,1 chr. 1q22-q2
Rat (Kcnj10): 379aa, Locus ID: 29718, GenBank: X83585, X86818, NM_031602, PMID: 7608203,2 7874445,3 chr. 13q24
Mouse (Kcnj10): 379aa, Locus ID: 16513, GenBank: AF322631, NM_020269, PMID: 11169792,5 chr. 1, 93.5 centimorgans
Associated subunits Kir4.2,1 Kir5.1,6 and Kir2.17 to form heteromeric channels; no auxiliary subunit is reported
Interacting proteins CIPP,8 α-syntrophin,9 possibly laminin and insulin,10 PKA, PKC (C. Lossin and Y. Kurachi, unpublished data)
Functional assays Voltage-clamp
Current IKir4.1
Conductance Various subconductances in homomeric and heteromeric channels; main conductance expression system-dependent: ≈ 20pS in 152 mM symmetric K+ in mammalian cells (C. Lossin and Y. Kurachi, unpublished data), ≈ 40pS in oocytes,11 40pS for mouse Kir4.1/5.1 heteromers in 145 mM symmetric K+12
Ion selectivity K+
Activation Constitutively open; enhanced by ATP2
Inactivation Voltage-dependent, blocked by Mg2+7 and polyamines13 (putrescine, spermine, and spermidine) at positive potentials
Activators ATP, PIP2 (in Kir4.1/5.1 heteromers)14
Gating inhibitors None
Blockers Ba2+ (IC50 at -100 mV),15 human Kir4.1: 3 μM, human 4.1/5.1: 8 μM; Cs+ (IC50 at -100 mV),16 human Kir4.1: 460 μM, human 4.1/5.1: 650 μM, intracellular H+ (pKa as specified below), Kir4.1: pKa 6.0,13 Kir4.1/5.1: pKa 7.514
Radioligands None
Channel distribution Glial, enriched around blood vessels and synapses,17 retina,10,18 ear,19 kidney20
Physiological functions Kir4.1 function has been implicated in glial K+ buffering in the brain in general18 and in K+ homeostasis in the inner ear and the kidney21; colocalization with aquaporin-4 proposes a role in water homeostasis22; also suggested is a contribution to oligodendrocyte development and myelination23; heteromeric Kir4.1/5.1 channels have been proposed to act as brainstem CO2 sensors14
Mutations and pathophysiology Knockout of Kir4.1 results in retinal defects,24 loss of the endocochlear potential25 with an otherwise normal phenotype; various studies have identified KCNJ10 as a possible epilepsy locus conferring susceptibility26 or resistance27 to hyperexcitability
Pharmacological significance Not established
Comments The salmon homolog (D83537) of mammalian Kir4.1 has been given the nomenclature Kir4.328

  • aa, amino acids; chr., chromosome; PKA, protein kinase A; protein kinase C.

  • ↵1. Shuck ME, Piser TM, Bock JH, Slightom JL, Lee KS, and Bienkowski MJ (1997) Cloning and characterization of two K+ inward rectifier (Kir) 1.1 potassium channel homologs from human kidney (Kir1.2 and Kir1.3). J Biol Chem 272:586-593

  • ↵2. Takumi T, Ishii T, Horio Y, Morishige K, Takahashi N, Yamada M, Yamashita T, Kiyama H, Sohmiya K, Nakanishi S, and Kurachi Y (1995) A novel ATP-dependent inward rectifier potassium channel expressed predominantly in glial cells. J Biol Chem 270:16339-16346

  • ↵3. Bond CT, Pessia M, Xia XM, Lagrutta A, Kavanaugh MP, and Adelman JP (1994) Cloning and expression of a family of inward rectifier potassium channels. Receptors Channels 2:183-191

  • ↵4. Bredt DS, Wang TL, Cohen NA, Guggino WB, and Snyder SH (1995) Cloning and expression of two brain-specific inwardly rectifying potassium channels. Proc Natl Acad Sci USA 92:6753-6757

  • ↵5. Li L, Head V, and Timpe LC (2001) Identification of an inward rectifier potassium channel gene expressed in mouse cortical astrocytes. Glia 33:57-71

  • ↵6. Pearson WL, Dourado M, Schreiber M, Salkoff L, and Nichos CG (1999) Expression of a functional Kir4 family inward rectifier K+ channel from a gene cloned from mouse liver. J Physiol 514:639-653

  • ↵7. Fakler B, Bond CT, Adelman JP, and Ruppersberg JP (1996) Heterooligomeric assembly of inward-rectifier K+ channels from subunits of different subfamilies: Kir2.1 (IRK1) and Kir4.1 (BIR10). Pflueg Arch Eur J Physiol 433:77-83

  • ↵8. Kurschner C, Mermelstein PG, Holden WT, and Surmeier DJ (1998) CIPP, a novel multivalent PDZ domain protein, selectively interacts with Kir4.0 family members, NMDA receptor subunits, neurexins, and neuroligins. Mol Cell Neurosci 11:161-172

  • ↵9. Connors NC, Adams ME, Froehner SC, and Kofuji P (2004) The potassium channel Kir4.1 associates with the dystrophin-glycoprotein complex via α-syntrophin in glia. J Biol Chem 279:28387-28392

  • ↵10. Ishii M, Horio Y, Tada Y, Hibino H, Inanobe A, Ito M, Yamada M, Gotow T, Uchiyama Y, and Kurachi Y (1997) Expression and clustered distribution of an inwardly rectifying potassium channel KAB-2/Kir4.1 on mammalian retinal Müller cell membrane: their regulation by insulin and laminin signals. J Neurosci 17:7725-7735

  • ↵11. Pessia M, Tucker SJ, Lee K, Bond CT, and Adelman JP (1996) Subunit positional effects revealed by novel heteromeric inwardly rectifying K+ channels. EMBO J 15:2980-2987

  • ↵12. Lourdel S, Paulais M, Cluzeaud F, Bens M, Tanemoto M, Kurachi Y, Vandewalle A, and Teulon J (2002) An inward rectifier K+ channel at the basolateral membrane of the mouse distal convoluted tubule: similarities with Kir4.1-Kir5.1 heteromeric channels. J Physiol 538:391-404

  • ↵13. Lopatin AN, Makhina EN, and Nichols CG (1994) Potassium channel block by cytoplasmic polyamines as the mechanism of intrinsic rectification. Nature (Lond) 372:366-369

  • ↵14. Yang Z, Xu H, Cui N, Qu Z, Chanchevalap S, Shen W, and 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

  • ↵15. Hagiwara S, Miyazaki S, Moody W, and Patlak J (1978) Blocking effects of barium and hydrogen ions on the potassium current during anomalous rectification in the starfish egg. J Physiol 279:167-185

  • ↵16. Hagiwara S, Miyazaki S, and Rosenthal NP (1976) Potassium current and the effect of cesium on this current during anomalous rectification of the egg cell membrane of a starfish. J Gen Physiol 67: 621-638

  • ↵17. Higashi K, Fujita A, Inanobe A, Tanemoto M, Doi K, Kubo T, and 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

  • ↵18. Brew H, Gray PT, Mobbs P, and Attwell D (1986)End feet of retinal glial cells have higher densities of ion channels that mediate K+ buffering. Nature (Lond) 324:466-468

  • ↵19. Hibino H, Horio Y, Fujita A, Inanobe A, Doi K, Gotow T, Uchiyama Y, Kubo T, and Kurachi Y (1999) Expression of an inwardly rectifying K+ channel, Kir4.1, in satellite cells of rat cochlear ganglia. Am J Physiol 277:C638-C644

  • ↵20. Ito M, Inanobe A, Horio Y, Hibino H, Isomoto S, Ito H, Mori K, Tonosaki A, Tomoike H, and Kurachi Y (1996) Immunolocalization of an inwardly rectifying K+ channel KAB-2 (Kir4.1), in the basolateral membrane of renal distal tubular epithelia. FEBS Lett 388:11-15

  • ↵21. Fujita A, Horio Y, Higashi K, Mouri T, Hata F, Takeguchi N, and Kurachi Y (2002) Specific localization of an inwardly rectifying K+ channel, Kir4.1, at the apical membrane of rat gastric parietal cells; its possible involvement in K+ recycling for the H+-K+-pump. J Physiol 540:85-92

  • ↵22. Nagelhus EA, HorioY, Inanobe A, Fujita A, Haug FM, Nielsen S, Kurachi Y, and Ottersen OP. Immunogold evidence suggests that coupling of K+ siphoning and water transport in rat retinal Müller cells is mediated by a coenrichment of Kir4.1 and AQP4 in specific membrane domains. Glia 26:47-54

  • ↵23. Neusch C, Rozengurt N, Jacobs RE, Lester HA, and Kofuji P (2001) Kir4.1 potassium channel subunit is crucial for oligodendrocyte development and in vivo myelination. J Neurosci 21:5429-5438

  • ↵24. Kofuji P, Ceelen P, Zahs KR, Surbeck LW, Lester HA, and 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

  • ↵25. Wangemann P, Itza EM, Albrecht B, Wu T, Jabba SV, Maganti RJ, Lee JH, Everett LA, Wall SM, Royaux IE, et al. (2004) Loss of KCNJ10 protein expression abolishes endocochlear potential and causes deafness in Pendred syndrome mouse model. BMC Med 2:30

  • ↵26. Ferraro TN, Golden GT, Smith GG, Martin JF, Lohoff FW, Gieringer TA, Zamboni D, Schwebel CL, Press DM, Kratzer SO, et al. (2004) Fine mapping of a seizure susceptibility locus on mouse chromosome 1: nomination of Kcnj10 as a causative gene. Mamm Genome 15:239-251

  • ↵27. Buono RJ, Lohoff FW, Sander T, Sperling MR, O'Connor MJ, Dlugos DJ, Ryan SG, Golden GT, Zhao H, Scattergood TM, et al. (2004) Association between variation in the human KCNJ10 potassium ion channel gene and seizure susceptibility. Epilepsy Res 58:175-83

  • ↵28. Kubo Y, Miyashita T, and Kubokawa K (1996) A weakly inward rectifying potassium channel of the salmon brain. J Biol Chem 271:15729-15735