Gene Symbol: Kcnj5
Description: potassium inwardly-rectifying channel, subfamily J, member 5
Alias: GIRK4, Kir3.4, G protein-activated inward rectifier potassium channel 4, CIR, GIRK-4, KATP-1, cardiac inward rectifier, heart KATP channel, inward rectifier K(+) channel Kir3.4, potassium channel, inwardly rectifying subfamily J member 5
Species: mouse
Products:     Kcnj5

Top Publications

  1. Posokhova E, Wydeven N, Allen K, Wickman K, Martemyanov K. RGS6/G?5 complex accelerates IKACh gating kinetics in atrial myocytes and modulates parasympathetic regulation of heart rate. Circ Res. 2010;107:1350-4 pubmed publisher
    ..Molecular mechanisms regulating this critical signal transduction pathway are not fully understood...
  2. Wickman K, Nemec J, Gendler S, Clapham D. Abnormal heart rate regulation in GIRK4 knockout mice. Neuron. 1998;20:103-14 pubmed
    ..regulation in vivo, we generated a mouse line deficient in I(KACh) by targeted disruption of the gene coding for GIRK4, one of the channel subunits...
  3. Kovoor P, Wickman K, Maguire C, Pu W, Gehrmann J, Berul C, et al. Evaluation of the role of I(KACh) in atrial fibrillation using a mouse knockout model. J Am Coll Cardiol. 2001;37:2136-43 pubmed
    ..It is likely that I(KACh) plays a crucial role in the generation of AF in mice. Specific I(KACh) blockers might be useful for the treatment of AF without significant adverse effects on the atrioventricular node or the ventricles. ..
  4. Gu Z, Gilbert D, Valentine V, Jenkins N, Copeland N, Zambetti G. The p53-inducible gene EI24/PIG8 localizes to human chromosome 11q23 and the proximal region of mouse chromosome 9. Cytogenet Cell Genet. 2000;89:230-3 pubmed
    ..These results suggest that EI24 may play an important role in the p53 tumor suppressor pathway. ..
  5. Wickman K, Seldin M, Gendler S, Clapham D. Partial structure, chromosome localization, and expression of the mouse Girk4 gene. Genomics. 1997;40:395-401 pubmed
    ..IKACh is composed of two homologous subunits, GIRK1 and GIRK4. Here we describe a partial genomic structure of the mouse Girk4 gene...
  6. Xu S, Kim J, Hwang K, Das R, Quan X, Nguyen T, et al. Autocrine insulin increases plasma membrane K(ATP) channel via PI3K-VAMP2 pathway in MIN6 cells. Biochem Biophys Res Commun. 2015;468:752-7 pubmed publisher
    ..Insulin-induced suppression of [Ca(2+)]i oscillation was prevented by an insulin receptor blocker. These results provide a novel molecular mechanism for autocrine negative feedback regulation of insulin secretion. ..
  7. Kobayashi T, Ikeda K, Kojima H, Niki H, Yano R, Yoshioka T, et al. Ethanol opens G-protein-activated inwardly rectifying K+ channels. Nat Neurosci. 1999;2:1091-7 pubmed
    ..Moreover, weaver mutant mice, which have a missense mutation in the GIRK2 channel, showed a loss of ethanol-induced analgesia. These results suggest that the GIRK channels in the brain and heart are important target sites for ethanol. ..
  8. Wickman K, Karschin C, Karschin A, Picciotto M, Clapham D. Brain localization and behavioral impact of the G-protein-gated K+ channel subunit GIRK4. J Neurosci. 2000;20:5608-15 pubmed
    ..The localization pattern of GIRK4, however, remains controversial...
  9. Wickman K, Pu W, Clapham D. Structural characterization of the mouse Girk genes. Gene. 2002;284:241-50 pubmed
    ..While the mouse Girk1 and Girk2 genes are relatively large (>100 kb), mouse Girk3 and Girk4 genes are compact (<20 kb)...

More Information


  1. Lesage F, Duprat F, Fink M, Guillemare E, Coppola T, Lazdunski M, et al. Cloning provides evidence for a family of inward rectifier and G-protein coupled K+ channels in the brain. FEBS Lett. 1994;353:37-42 pubmed
    ..These results provide the first evidence that the GIRK family, as the IRK family, is composed of multiple genes with members specifically expressed in the nervous system. ..
  2. Mesirca P, Bidaud I, Briec F, Evain S, Torrente A, Le Quang K, et al. G protein-gated IKACh channels as therapeutic targets for treatment of sick sinus syndrome and heart block. Proc Natl Acad Sci U S A. 2016;113:E932-41 pubmed publisher
    ..Our data suggest that patients affected by SSS and heart block may benefit from IKACh suppression achieved by gene therapy or selective pharmacological inhibition. ..
  3. Perry C, Pravetoni M, Teske J, Aguado C, Erickson D, Medrano J, et al. Predisposition to late-onset obesity in GIRK4 knockout mice. Proc Natl Acad Sci U S A. 2008;105:8148-53 pubmed publisher
    ..Four Girk genes have been identified (Girk1-4). Whereas GIRK4 is associated with the cardiac GIRK channel, Girk4 expression has been detected in a few neuron populations...
  4. Nobles M, Sebastian S, Tinker A. HL-1 cells express an inwardly rectifying K+ current activated via muscarinic receptors comparable to that in mouse atrial myocytes. Pflugers Arch. 2010;460:99-108 pubmed publisher
    ..Using immunofluorescence, we found GIRK4 at the membrane in HL-1 cells...
  5. Graciotti L, Becker J, Granata A, Procopio A, Tessarollo L, Fulgenzi G. Dystrophin is required for the normal function of the cardio-protective K(ATP) channel in cardiomyocytes. PLoS ONE. 2011;6:e27034 pubmed publisher
    ..Therefore, the lack of proper functioning of the cardio-protective K(ATP) system in the mdx cardiomyocytes may be part of the mechanism contributing to development of cardiac disease in dystrophic patients. ..
  6. Toib A, Zhang H, Broekelmann T, Hyrc K, Guo Q, Chen F, et al. Cardiac specific ATP-sensitive K+ channel (KATP) overexpression results in embryonic lethality. J Mol Cell Cardiol. 2012;53:437-45 pubmed publisher
    ..These results suggest that the K(ATP) channel may have an important physiological role during early cardiac development. ..
  7. Georgiadis K, Hirohata S, Seldin M, Apte S. ADAM-TS8, a novel metalloprotease of the ADAM-TS family located on mouse chromosome 9 and human chromosome 11. Genomics. 1999;62:312-5 pubmed
    ..Through analysis of an interspecific backcross panel, we place the Adamts8 locus on mouse chromosome 9 at a consensus position of 11 cM and its human ortholog, recently reported as the METH2 gene, on human chromosome 11q25. ..
  8. Pecker I, Avraham K, Gilbert D, Savitsky K, Rotman G, Harnik R, et al. Identification and chromosomal localization of Atm, the mouse homolog of the ataxia-telangiectasia gene. Genomics. 1996;35:39-45 pubmed
    ..Fluorescence in situ hybridization and linkage analysis located the Atm gene on mouse chromosome 9, band 9C, in a region homologous to the ATM region on human chromosome 11q22-q23. ..
  9. Szpirer C, Molné M, Antonacci R, Jenkins N, Finelli P, Szpirer J, et al. The genes encoding the glutamate receptor subunits KA1 and KA2 (GRIK4 and GRIK5) are located on separate chromosomes in human, mouse, and rat. Proc Natl Acad Sci U S A. 1994;91:11849-53 pubmed
    ..Our data extend the conserved synteny established between certain human, mouse, and rat Chrs. ..
  10. Liang B, Nissen J, Laursen M, Wang X, Skibsbye L, Hearing M, et al. G-protein-coupled inward rectifier potassium current contributes to ventricular repolarization. Cardiovasc Res. 2014;101:175-84 pubmed publisher
    ..Immunofluorescence experiments demonstrated that GIRK4 was localized in outer sarcolemmas and t-tubules in GIRK1 knockout (KO) mice, whereas GIRK4 labelling was not ..
  11. Mesirca P, Alig J, Torrente A, Müller J, Marger L, Rollin A, et al. Cardiac arrhythmia induced by genetic silencing of 'funny' (f) channels is rescued by GIRK4 inactivation. Nat Commun. 2014;5:4664 pubmed publisher
    ..of impulse generation and conduction by additional genetic deletion of cardiac muscarinic G-protein-activated (GIRK4) channels in If-deficient mice without impairing heartbeat regulation...
  12. Fleischmann B, Duan Y, Fan Y, Schoneberg T, Ehlich A, Lenka N, et al. Differential subunit composition of the G protein-activated inward-rectifier potassium channel during cardiac development. J Clin Invest. 2004;114:994-1001 pubmed
    ..4 subunit. Thus, a switch in subunit composition is used to adopt IK,ACh to its functional role in adult cardiomyocytes. ..
  13. Fernandez Alacid L, Aguado C, Ciruela F, Martín R, Colon J, Cabañero M, et al. Subcellular compartment-specific molecular diversity of pre- and post-synaptic GABA-activated GIRK channels in Purkinje cells. J Neurochem. 2009;110:1363-76 pubmed publisher
    ..The association of GIRK channels and GABA(B) receptors with excitatory synapses at both post- and pre-synaptic sites indicates their intimate involvement in the modulation of glutamatergic neurotransmission in the cerebellum. ..
  14. Labouèbe G, Lomazzi M, Cruz H, Creton C, Lujan R, Li M, et al. RGS2 modulates coupling between GABAB receptors and GIRK channels in dopamine neurons of the ventral tegmental area. Nat Neurosci. 2007;10:1559-68 pubmed
    ..Finally, oral self-administration of GHB at a concentration that is normally rewarding becomes aversive after chronic exposure. On the basis of these results, we propose a mechanism that might underlie tolerance to GHB...
  15. Frankel W, Beyer B, Maxwell C, Pretel S, Letts V, Siegel S. Development of a new genetic model for absence epilepsy: spike-wave seizures in C3H/He and backcross mice. J Neurosci. 2005;25:3452-8 pubmed
    ..Because C3H/He mice have no other brain abnormalities, they are an attractive alternative for studying idiopathic absence epilepsy. ..
  16. Marker C, Cintora S, Roman M, Stoffel M, Wickman K. Hyperalgesia and blunted morphine analgesia in G protein-gated potassium channel subunit knockout mice. Neuroreport. 2002;13:2509-13 pubmed
    ..2 subunit contributes to the analgesia evoked by a moderate dose of morphine. As such, receptor-independent Kir3 channel agonists may represent a novel and selective class of analgesic agent. ..
  17. Bettahi I, Marker C, Roman M, Wickman K. Contribution of the Kir3.1 subunit to the muscarinic-gated atrial potassium channel IKACh. J Biol Chem. 2002;277:48282-8 pubmed
    ..We conclude that Kir3.1 confers properties to I(KACh) that enhance channel activity and that Kir3.4 homomultimers do not contribute significantly to the muscarinic-gated potassium current. ..
  18. Aguado C, Colon J, Ciruela F, Schlaudraff F, Cabañero M, Perry C, et al. Cell type-specific subunit composition of G protein-gated potassium channels in the cerebellum. J Neurochem. 2008;105:497-511 pubmed
    ..neuron populations, including Purkinje neurons (GIRK1/GIRK2/GIRK3), basket cells (GIRK1/GIRK3), Golgi cells (GIRK2/GIRK4), stellate cells (GIRK3), and unipolar brush cells (GIRK2/GIRK3)...
  19. Stoller D, Fahrenbach J, Chalupsky K, Tan B, Aggarwal N, Metcalfe J, et al. Cardiomyocyte sulfonylurea receptor 2-KATP channel mediates cardioprotection and ST segment elevation. Am J Physiol Heart Circ Physiol. 2010;299:H1100-8 pubmed publisher
    ..Therefore, cardioprotective mechanisms both dependent and independent of SUR2-K(ATP) channels contribute to cardiac function...
  20. Lesage F, Guillemare E, Fink M, Duprat F, Heurteaux C, Fosset M, et al. Molecular properties of neuronal G-protein-activated inwardly rectifying K+ channels. J Biol Chem. 1995;270:28660-7 pubmed
    ..A Na+ binding site on the cytoplasmic face of the membrane acts in synergy with the ATP binding site to stabilize channel activity. ..
  21. Posokhova E, Ng D, Opel A, Masuho I, Tinker A, Biesecker L, et al. Essential role of the m2R-RGS6-IKACh pathway in controlling intrinsic heart rate variability. PLoS ONE. 2013;8:e76973 pubmed publisher
    ..These findings identify the essential role of the m2R-I(KACh) signaling pathway in the regulation of cardiac sinus rhythm and implicate RGS6 in arrhythmia pathogenesis. ..
  22. Sowell M, Ye C, Ricupero D, Hansen S, Quinn S, Vassilev P, et al. Targeted inactivation of alphai2 or alphai3 disrupts activation of the cardiac muscarinic K+ channel, IK+Ach, in intact cells. Proc Natl Acad Sci U S A. 1997;94:7921-6 pubmed
    ..Also the generation of negative chronotropic responses to muscarinic or adenosine receptor agonists do not require activation of IK+Ach or the expression of alphai2 or alphai3. ..
  23. Kofuji P, Hofer M, Millen K, Millonig J, Davidson N, Lester H, et al. Functional analysis of the weaver mutant GIRK2 K+ channel and rescue of weaver granule cells. Neuron. 1996;16:941-52 pubmed
    ..Pharmacological blockade of the Na+ influx in weaver granule cells restores their ability to differentiate normally. Thus, Na+ flux through the weaver GIRK2 channel underlies the failure of granule cell development in situ. ..
  24. Wang D, Liu C, Li Z, Wang Y, Wang W, Wu X, et al. Regulation of Histone Acetylation on Expression Profiles of Potassium Channels During Cardiomyocyte Differentiation From Mouse Embryonic Stem Cells. J Cell Biochem. 2017;118:4460-4467 pubmed publisher
    ..induced by Class I HDACs inhibitors promoted the expression profiles of potassium channels (Kcnj2, Kcnj3, Kcnj5, Kcnj11, and Kcnh2) in the process...