Genomes and Genes
Gene Symbol: Kcnj10
Description: potassium voltage-gated channel subfamily J member 10
Alias: ATP-sensitive inward rectifier potassium channel 10, ATP-sensitive inward rectifier potassium channel KAB-2, BIR10, BIRK1, brain-specific inwardly rectifying K(+) channel 1, inward rectifier K(+) channel Kir4.1, kir4.1, potassium channel, inwardly rectifying subfamily J member 10, potassium inwardly-rectifying channel, subfamily J, member 10
- Ren H, Xu G, Qian J, Zhou M, Gonzales J, Ni Y. Müller cells upregulate the expression of SAP97 in light-injured rat retina. Neuroreport. 2010;21:832-6 pubmed publisher..05). The upregulation of SAP97 coincides with the redistribution of AQP4 and Kir4.1 in blue light-injured rat retina. ..
- Cha S, Huang C, Ding Y, Qi X, Huang C, Miller R. Calcium-sensing receptor decreases cell surface expression of the inwardly rectifying K+ channel Kir4.1. J Biol Chem. 2011;286:1828-35 pubmed publisher..Thus, the CaR decreases cell surface expression of Kir4.1 channels via a mechanism that involves G?(q) and caveolin. These results provide a novel molecular basis for the inhibition of renal NaCl transport by the CaR. ..
- Huang C, Sindic A, Hill C, Hujer K, Chan K, Sassen M, et al. Interaction of the Ca2+-sensing receptor with the inwardly rectifying potassium channels Kir4.1 and Kir4.2 results in inhibition of channel function. Am J Physiol Renal Physiol. 2007;292:F1073-81 pubmed..The CaR interacts directly with Kir4.1 and Kir4.2 and can decrease their currents, which in turn could reduce recycling of K(+) for the basolateral Na(+)-K(+)-ATPase and thereby contribute to inhibition of Na(+) reabsorption. ..
- Kaufhold M, Krabbenhöft A, Song P, Engelhardt R, Riederer B, Fährmann M, et al. Localization, trafficking, and significance for acid secretion of parietal cell Kir4.1 and KCNQ1 K+ channels. Gastroenterology. 2008;134:1058-69 pubmed publisher..The close association of Kir4.1 channels with H(+)/K(+)-ATPase in the resting and stimulated membrane suggests a possible role for Kir4.1 channels during the acid secretory cycle. ..
- Harada Y, Nagao Y, Shimizu S, Serikawa T, Terada R, Fujimoto M, et al. Expressional analysis of inwardly rectifying Kir4.1 channels in Noda epileptic rat (NER). Brain Res. 2013;1517:141-9 pubmed publisher..1 expression showed a marked elevation of Fos protein expression following GTC seizures. The present results suggest that reduced activity of astrocytic Kir4.1 channels in the amygdala is involved in limbic hyperexcitability in NERs. ..
- Yan J, Khatibi N, Han H, Hu Q, Chen C, Li L, et al. p53-induced uncoupling expression of aquaporin-4 and inwardly rectifying K+ 4.1 channels in cytotoxic edema after subarachnoid hemorrhage. CNS Neurosci Ther. 2012;18:334-42 pubmed publisher..These results indicated p53 mediates the formation of cytotoxic edema in the brain following SAH; an uncoupling expression of AQP4 and Kir4.1 on astrocytic end feet orchestrated by p38MAPK was partly responsible. ..
- Najafi E, Stoodley M, Bilston L, Hemley S. Inwardly rectifying potassium channel 4.1 expression in post-traumatic syringomyelia. Neuroscience. 2016;317:23-35 pubmed publisher..It is possible this contributes to water accumulation in the injured spinal cord leading to syrinx formation or exacerbation of the underlying pathology. ..
- Iandiev I, Wurm A, Hollborn M, Wiedemann P, Grimm C, Reme C, et al. Müller cell response to blue light injury of the rat retina. Invest Ophthalmol Vis Sci. 2008;49:3559-67 pubmed publisher..The decrease in functional Kir channels may result in a disturbance of retinal potassium and water homeostasis, contributing to the degenerative alterations of the inner retina after exposure to blue light. ..
- Xie B, Jiao Q, Cheng Y, Zhong Y, Shen X. Effect of pigment epithelium-derived factor on glutamate uptake in retinal Muller cells under high-glucose conditions. Invest Ophthalmol Vis Sci. 2012;53:1023-32 pubmed publisher..These findings suggest that PEDF acts as an antioxidative agent against the decrease in Kir4.1 and GLAST expression and compromise of glutamate uptake activity in retinal Müller cells in diabetic conditions. ..
- Dibas A, Oku H, Fukuhara M, Kurimoto T, Ikeda T, Patil R, et al. Changes in ocular aquaporin expression following optic nerve crush. Mol Vis. 2010;16:330-40 pubmed..Changes in AQP9 expression suggest a contribution of the channel to retinal ganglion cell death and response of distinct amacrine cells known to express AQP9 following traumatic injuries. ..
- Nakajima M, Kawamura T, Tokui R, Furuta K, Sugino M, Nakanishi M, et al. Enhanced accumulation of Kir4.1 protein, but not mRNA, in a murine model of cuprizone-induced demyelination. Brain Res. 2013;1537:340-9 pubmed publisher..These findings suggest that enhanced accumulation of Kir4.1 protein in the brain with an inflammatory condition facilitates the autoantibody formation against Kir4.1 in patients with multiple sclerosis. ..
- Tanemoto M, Abe T, Ito S. PDZ-binding and di-hydrophobic motifs regulate distribution of Kir4.1 channels in renal cells. J Am Soc Nephrol. 2005;16:2608-14 pubmed..1 homomer and Kir5.1/Kir4.1 heteromer in MDCK cells, they are thought to be responsible for the localization of basolateral K+ channel in renal distal tubules. ..
- Obara Michlewska M, Ruszkiewicz J, ZieliÅ„ska M, Verkhratsky A, Albrecht J. Astroglial NMDA receptors inhibit expression of Kir4.1 channels in glutamate-overexposed astrocytes in vitro and in the brain of rats with acute liver failure. Neurochem Int. 2015;88:20-5 pubmed publisher..1 expression in CNS disorders associated with increased exposure to Glu. ..
- Berner A, Brouwers O, Pringle R, Klaassen I, Colhoun L, McVicar C, et al. Protection against methylglyoxal-derived AGEs by regulation of glyoxalase 1 prevents retinal neuroglial and vasodegenerative pathology. Diabetologia. 2012;55:845-54 pubmed publisher..Using a transgenic rat model that overexpresses GLO1, we investigated if this enzyme can inhibit retinal AGE formation and prevent key lesions of diabetic retinopathy...
- Sun M, Wang H, Qi Q, Yan H, Zou W, Dong X, et al. [IL-1? promotes the proliferation of astrocytes and downregulates the expression of Kir4.1]. Xi Bao Yu Fen Zi Mian Yi Xue Za Zhi. 2017;33:446-449 pubmed..1 mRNA and protein expressions could be partially reverted when IL-1? was removed. Conclusion IL-1? could promote the proliferation of cultured astrocytes, and IL-1? may be a key factor influencing the expression of Kir4.1 in astrocytes. ..
- Rozengurt N, Lopez I, Chiu C, Kofuji P, Lester H, Neusch C. Time course of inner ear degeneration and deafness in mice lacking the Kir4.1 potassium channel subunit. Hear Res. 2003;177:71-80 pubmedThe Kir4.1 gene (KCNJ10) encodes an inwardly rectifying K(+) channel subunit abundantly expressed in the CNS. Its expression in the mammalian inner ear has been suggested but its function in vivo in the inner ear is unknown...
- Lanciotti A, Brignone M, Camerini S, Serafini B, Macchia G, Raggi C, et al. MLC1 trafficking and membrane expression in astrocytes: role of caveolin-1 and phosphorylation. Neurobiol Dis. 2010;37:581-95 pubmed publisher..Because pathological mutations prevent MLC1 membrane expression, the identification of substances regulating MLC1 intracellular trafficking is potentially relevant for the therapy of MLC. ..
- Takumi T, Ishii T, Horio Y, Morishige K, Takahashi N, Yamada M, et al. A novel ATP-dependent inward rectifier potassium channel expressed predominantly in glial cells. J Biol Chem. 1995;270:16339-46 pubmed..This is the first description of the cloning of a glial cell inward rectifier potassium channel, which may be responsible for K+ buffering action of glial cells in the brain. ..
- Fujita A, Inanobe A, Hibino H, Nielsen S, Ottersen O, Kurachi Y. Clustering of Kir4.1 at specialized compartments of the lateral membrane in ependymal cells of rat brain. Cell Tissue Res. 2015;359:627-634 pubmed publisher..We propose that ependymal cells and tanycytes differentially operate Kir4.1 and AQP4 actively to control the property of fluids at local areas in the brain. ..
- Kalsi A, Greenwood K, Wilkin G, Butt A. Kir4.1 expression by astrocytes and oligodendrocytes in CNS white matter: a developmental study in the rat optic nerve. J Anat. 2004;204:475-85 pubmed..1 channels are not involved in K(+) regulation. The results support roles for Kir4.1 in both oligodendrocyte differentiation and K(+) regulation by astrocytes. ..
- Tanemoto M, Kittaka N, Inanobe A, Kurachi Y. In vivo formation of a proton-sensitive K+ channel by heteromeric subunit assembly of Kir5.1 with Kir4.1. J Physiol. 2000;525 Pt 3:587-92 pubmed..1 with Kir4.1 occurs in vivo, at least in kidney. The heteromeric Kir4. 1/Kir5.1 channel may therefore sense intracellular pH in renal epithelium and be involved in the regulation of acid-base homeostasis. ..
- MÃ©ndez GonzÃ¡lez M, Kucheryavykh Y, Zayas Santiago A, VÃ©lez Carrasco W, Maldonado MartÃnez G, Cubano L, et al. Novel KCNJ10 Gene Variations Compromise Function of Inwardly Rectifying Potassium Channel 4.1. J Biol Chem. 2016;291:7716-26 pubmed publisher..1 channels achieved a higher block than WT, suggesting a more stable interaction of SPM in the deep pore cavity. Overall, our data suggest that G83V, L166Q, and Q212R residues play a pivotal role in controlling Kir4.1 channel function. ..
- Hassan I, Luo Q, Majumdar S, Dominguez J, Busik J, Bhatwadekar A. Tumor Necrosis Factor Alpha (TNF-?) Disrupts Kir4.1 Channel Expression Resulting in Müller Cell Dysfunction in the Retina. Invest Ophthalmol Vis Sci. 2017;58:2473-2482 pubmed publisher..Our findings demonstrate that Kir4.1 channels possess a diurnal rhythm, and this rhythm is dampened with diabetes, thereby suggesting that the increase in TNF-? is detrimental to normal Kir4.1 rhythm and expression. ..
- Bredt D, Wang T, Cohen N, Guggino W, Snyder S. Cloning and expression of two brain-specific inwardly rectifying potassium channels. Proc Natl Acad Sci U S A. 1995;92:6753-7 pubmed..b>BIRK1 mRNA is extremely abundant and is enriched in specific brainstem nuclei, BIRK1 displays a consensus phosphate-..
- Tanemoto M, Abe T, Onogawa T, Ito S. PDZ binding motif-dependent localization of K+ channel on the basolateral side in distal tubules. Am J Physiol Renal Physiol. 2004;287:F1148-53 pubmed..1 was responsible for this intracellular localization. These data suggest the signals on the COOH terminus of Kir4.1, including PDZ binding motif, determine the intracellular localization of Kir5.1/Kir4.1 heteromer in distal tubules. ..
- Vit J, Ohara P, Bhargava A, Kelley K, Jasmin L. 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. 2008;28:4161-71 pubmed publisher..1 to treat pain in general and particularly neuropathic pain that occurs in the absence of nerve injury. ..
- Iandiev I, Tenckhoff S, Pannicke T, Biedermann B, Hollborn M, Wiedemann P, et al. Differential regulation of Kir4.1 and Kir2.1 expression in the ischemic rat retina. Neurosci Lett. 2006;396:97-101 pubmed..1 mRNA was not altered. The data suggest that the glial expression of distinct Kir channels is differentially regulated after retinal ischemia, with deletarious consequences for K+ ion and water homeostasis. ..
- Takiguchi Y, Sun G, Ogawa K, Matsunaga T. Long-lasting changes in the cochlear K+ recycling structures after acute energy failure. Neurosci Res. 2013;77:33-41 pubmed publisher..These results indicate long-lasting changes in the cochlear lateral wall and spiral limbus, which may compensate for damaged K(+) recycling and protect cells from ATP shortage. ..
- Wenker I, Kréneisz O, Nishiyama A, Mulkey D. 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. 2010;104:3042-52 pubmed publisher..We conclude that RTN astrocytes sense CO(2)/H(+) in part by inhibition of a Kir4.1-Kir5.1-like current and may provide an excitatory purinergic drive to pH-sensitive neurons. ..
- Sala Rabanal M, Kucheryavykh L, Skatchkov S, Eaton M, Nichols C. Molecular mechanisms of EAST/SeSAME syndrome mutations in Kir4.1 (KCNJ10). J Biol Chem. 2010;285:36040-8 pubmed publisher..These results provide an explanation for the molecular defects that underlie the EAST/SeSAME syndrome. ..
- Dong K, Tang L, MacGregor G, Leng Q, Hebert S. Novel nucleotide-binding sites in ATP-sensitive potassium channels formed at gating interfaces. EMBO J. 2005;24:1318-29 pubmed..The short N- and C-terminal segments comprising the novel intermolecular NBS are next to helices that likely move with channel opening/closing, suggesting a lock-and-key model for ligand gating. ..
- Bockenhauer D, Feather S, Stanescu H, Bandulik S, Zdebik A, Reichold M, et al. Epilepsy, ataxia, sensorineural deafness, tubulopathy, and KCNJ10 mutations. N Engl J Med. 2009;360:1960-70 pubmed publisher..2 with a lod score of 4.98. This region contained the KCNJ10 gene, which encodes a potassium channel expressed in the brain, inner ear, and kidney...
- Djukic B, Casper K, Philpot B, Chin L, McCarthy K. 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. 2007;27:11354-65 pubmed..1 cKO hippocampus. Our findings implicate a role for glial Kir4.1 channel subunit in the modulation of synaptic strength. ..
- Rehak M, Drechsler F, Köferl P, Hollborn M, Wiedemann P, Bringmann A, et al. Effects of intravitreal triamcinolone acetonide on retinal gene expression in a rat model of central retinal vein occlusion. Graefes Arch Clin Exp Ophthalmol. 2011;249:1175-83 pubmed publisher..Triamcinolone exerts anti-inflammatory effects in the ischemic retina by inhibitory effects on the gene expression of IL-1ß and IL-6, and may have neuroprotective effects via improvement of retinal potassium homeostasis. ..
- Zhang Y, Xu G, Ling Q, da C. Expression of aquaporin 4 and Kir4.1 in diabetic rat retina: treatment with minocycline. J Int Med Res. 2011;39:464-79 pubmed..1 levels. These findings suggest that minocycline might be beneficial for retinal fluid clearance and reduction of retinal oedema in diabetic retinopathy. ..
- Hirrlinger P, Ulbricht E, Iandiev I, Reichenbach A, Pannicke T. Alterations in protein expression and membrane properties during Müller cell gliosis in a murine model of transient retinal ischemia. Neurosci Lett. 2010;472:73-8 pubmed publisher..This murine high intraocular pressure model of transient retinal ischemia is proposed as a versatile tool for further studies on Müller cell functions in retinal degeneration...
- Neusch C, Papadopoulos N, Muller M, Maletzki I, Winter S, Hirrlinger J, et al. 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. 2006;95:1843-52 pubmed..To estimate the involvement of the weakly inwardly rectifying K+ channel Kir4.1 (KCNJ10) in extracellular K+ clearance, we examined its functional expression in astrocytes of the respiratory network...
- Hibino H, Fujita A, Iwai K, Yamada M, Kurachi Y. Differential assembly of inwardly rectifying K+ channel subunits, Kir4.1 and Kir5.1, in brain astrocytes. J Biol Chem. 2004;279:44065-73 pubmed..D'Adamo, M. C., and Pessia, M. (2000) J. Biol. Chem. 275, 16404-16407), it is plausible that these channels play differential physiological roles in the K+ -buffering action of brain astrocytes in a region-specific manner. ..
- Zhao M, Valamanesh F, Celerier I, Savoldelli M, Jonet L, Jeanny J, et al. The neuroretina is a novel mineralocorticoid target: aldosterone up-regulates ion and water channels in Müller glial cells. FASEB J. 2010;24:3405-15 pubmed publisher..These results provide a rationale for future investigations of abnormal MR signaling in the pathological retina. ..
- Zhang X, Su J, Cui N, Gai H, Wu Z, Jiang C. The disruption of central CO2 chemosensitivity in a mouse model of Rett syndrome. Am J Physiol Cell Physiol. 2011;301:C729-38 pubmed publisher..1 overexpression may not allow CO(2) to be detected until hypercapnia becomes severe, leading to periodical hyper- and hypoventilation in Mecp2-null mice and, perhaps, in people with RTT as well. ..
- Goodyear M, Crewther S, Murphy M, Giummarra L, Hazi A, Junghans B, et al. Spatial and temporal dissociation of AQP4 and Kir4.1 expression during induction of refractive errors. Mol Vis. 2010;16:1610-9 pubmed..1 channels appears to play a role in limiting axial elongation in the presence of plus lenses. ..
- Sun M, Yan H, Zou W, Wang Y, Li H, Wang X. [Lipopolysaccharide induces astrocyte activation and downregulates the expression of Kir4.1 channel]. Xi Bao Yu Fen Zi Mian Yi Xue Za Zhi. 2016;32:196-200 pubmed..The cultured astrocytes could be activated by LPS; LPS-induced downregulation of Kir4.1 mRNA in cultured astrocytes might be related with the inflammatory cytokine IL-1Î². ..
- Liu X, Kobayashi H, Jin Z, Wada A, Nao I N. Differential expression of Kir4.1 and aquaporin 4 in the retina from endotoxin-induced uveitis rat. Mol Vis. 2007;13:309-17 pubmed..1 and AQP4 in the retina. The differential expression of Kir4.1 and AQP4 during EIU implies a disturbance of water and potassium transport in the retina, which may contribute to the retinal edema during ocular inflammation. ..
- Reichold M, Zdebik A, Lieberer E, Rapedius M, Schmidt K, Bandulik S, et al. KCNJ10 gene mutations causing EAST syndrome (epilepsy, ataxia, sensorineural deafness, and tubulopathy) disrupt channel function. Proc Natl Acad Sci U S A. 2010;107:14490-5 pubmed publisherMutations of the KCNJ10 (Kir4.1) K(+) channel underlie autosomal recessive epilepsy, ataxia, sensorineural deafness, and (a salt-wasting) renal tubulopathy (EAST) syndrome...
- Nwaobi S, Lin E, Peramsetty S, Olsen M. DNA methylation functions as a critical regulator of Kir4.1 expression during CNS development. Glia. 2014;62:411-27 pubmed publisher..1 expression in rats is coincident with reductions in DNA methylation of the Kir4.1 gene, KCNJ10. Chromatin immunoprecipitation reveals a dynamic interaction between KCNJ10 and DNA methyltransferase 1 during ..
- Wu J, Marmorstein A, Kofuji P, Peachey N. Contribution of Kir4.1 to the mouse electroretinogram. Mol Vis. 2004;10:650-4 pubmed..1, normally opposes a positive polarity conductance that is generated by the apical membrane of the retinal pigment epithelium to form the c-wave measured at the corneal surface. ..
- Tang X, Schmidt T, Perez Leighton C, Kofuji P. Inwardly rectifying potassium channel Kir4.1 is responsible for the native inward potassium conductance of satellite glial cells in sensory ganglia. Neuroscience. 2010;166:397-407 pubmed publisher..1 is the principal Kir channel type in SGCs. Therefore Kir4.1 emerges as a key regulator of SGC function and possibly neuronal excitability in sensory ganglia. ..
- Shang L, Lucchese C, Haider S, Tucker S. Functional characterisation of missense variations in the Kir4.1 potassium channel (KCNJ10) associated with seizure susceptibility. Brain Res Mol Brain Res. 2005;139:178-83 pubmed..1 potassium channel (KCNJ10) and seizure susceptibility phenotypes in both humans and mice...
- Olsen M, Campbell S, McFerrin M, Floyd C, Sontheimer H. Spinal cord injury causes a wide-spread, persistent loss of Kir4.1 and glutamate transporter 1: benefit of 17 beta-oestradiol treatment. Brain. 2010;133:1013-25 pubmed publisher..1 and glutamate transporter 1 expression in astrocytes leading to improved potassium and glutamate homeostasis. ..
- Tanemoto M, Toyohara T, Abe T, Ito S. MAGI-1a functions as a scaffolding protein for the distal renal tubular basolateral K+ channels. J Biol Chem. 2008;283:12241-7 pubmed publisher..These results demonstrate that the phosphorylation-dependent scaffolding of the basolateral K(+) channels by MAGI-1a-long participates in the renal regulation of the fluid and electrolyte homeostasis. ..
- Takeda M, Takahashi M, Nasu M, Matsumoto S. Peripheral inflammation suppresses inward rectifying potassium currents of satellite glial cells in the trigeminal ganglia. Pain. 2011;152:2147-56 pubmed publisher..Therefore, the Kir4.1 channel in SGCs may be a new molecular target for the treatment of trigeminal inflammatory pain. ..
- Kucheryavykh Y, Kucheryavykh L, Nichols C, Maldonado H, Baksi K, Reichenbach A, et al. Downregulation of Kir4.1 inward rectifying potassium channel subunits by RNAi impairs potassium transfer and glutamate uptake by cultured cortical astrocytes. Glia. 2007;55:274-81 pubmed..Significant inhibition of glutamate clearance in astrocytes with knock-down of Kir4.1 highlights the role of membrane hyperpolarization in this process. ..
- Olsen M, Campbell S, Sontheimer H. Differential distribution of Kir4.1 in spinal cord astrocytes suggests regional differences in K+ homeostasis. J Neurophysiol. 2007;98:786-93 pubmed..Taken together, these data support the conclusion that regional differences in astrocytic expression of Kir4.1 channels result in marked changes in potassium clearance rates in these two regions of the spinal cord. ..
- Obara Michlewska M, Pannicke T, Karl A, Bringmann A, Reichenbach A, Szeliga M, et al. Down-regulation of Kir4.1 in the cerebral cortex of rats with liver failure and in cultured astrocytes treated with glutamine: Implications for astrocytic dysfunction in hepatic encephalopathy. J Neurosci Res. 2011;89:2018-27 pubmed publisher..The results indicate that down-regulation of Kir4.1 may mediate distinct aspects of Gln-induced astrocytic dysfunction in HE. ..
- Seifert G, Hüttmann K, Binder D, Hartmann C, Wyczynski A, Neusch C, et al. Analysis of astroglial K+ channel expression in the developing hippocampus reveals a predominant role of the Kir4.1 subunit. J Neurosci. 2009;29:7474-88 pubmed publisher..Together, our findings demonstrate that Kir4.1 constitutes the pivotal K+ channel subunit and that superposition of currents through Kir4.1 and TREK channels underlies the "passive" current pattern of hippocampal astrocytes. ..