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Kcnj11  -  potassium inwardly rectifying channel,...

Mus musculus

Synonyms: AI842722, ATP-sensitive inward rectifier potassium channel 11, AW491124, Inward rectifier K(+) channel Kir6.2, Kir6.2, ...
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Disease relevance of Kcnj11


Psychiatry related information on Kcnj11

  • The mild glucose intolerance that is observed in the Kir6.2 knockout mice is unlikely to have created the memory deficits observed [6].
  • Thus, our results suggest that loss of Kir6.2-containing K(ATP) channels does affect animal behavior under metabolic control conditions, especially in novel situations [7].
  • As a comprehensive behavioral description of Kir6.2 KO mice under physiological control conditions has not yet been carried out, we subjected Kir6.2 KO and corresponding wild-type (WT) mice to a test battery to assess emotional behavior, motor activity and coordination, species-typical behaviors and cognition [7].

High impact information on Kcnj11

  • Genetic inactivation of the K-ATP channel pore-forming subunit Kir6.2 resulted in a selective rescue of SN but not VTA DA neurons in two mechanistically distinct mouse models of dopaminergic degeneration, the neurotoxicological 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) model and the mutant weaver mouse [8].
  • Kir6.2 is the pore-forming subunit of K(ATP) channels in many cell types, including pancreatic beta-cells and heart [3].
  • Here we show the complete absence of both functional ATP-sensitive K+ (K(ATP)) channels and glucose responsiveness in the neurons of the ventromedial hypothalamus (VMH) in Kir6.2-/- mice [3].
  • The structure, in combination with molecular modelling, suggests how SUR1 interacts with Kir6.2 [9].
  • A molecular model of the C-terminus of Kir6.2 (based on the crystal structure of Kir3.1) was constructed and automated docking was used to identify residues interacting with ATP [10].

Biological context of Kcnj11

  • MATERIALS AND METHODS: Heterozygous Kir6.2(+/-) and SUR1(+/-) animals were generated by backcrossing from knockout animals [1].
  • CONCLUSIONS/INTERPRETATION: A significant proportion of Kir6.2 and SUR1 subunits reside on insulin-secretory vesicles and the distal secretory pathway in mouse beta cells but do not influence intravesicular ion homeostasis [11].
  • Identification of residues contributing to the ATP binding site of Kir6.2 [10].
  • Using cysteine-scanning mutagenesis and charged thiol-modifying reagents, we identified two amino acids in Kir6.2 that appear to interact directly with ATP: R50 in the N-terminus, and K185 in the C-terminus [10].
  • Here, upon catecholamine challenge, disruption of KATP channels, by genetic deletion of the pore-forming Kir6.2 subunit, produced defective cardiac action potential shortening, predisposing the myocardium to early afterdepolarizations [12].

Anatomical context of Kcnj11


Associations of Kcnj11 with chemical compounds

  • In contrast, pretreatment with glucagon-like peptide-1 (GLP-1) in Kir6.2(-/-) mice potentiated insulin secretion and blunted the rise in blood glucose levels [16].
  • We have generated transgenic mice expressing a dominant-negative form of the KATP channel subunit Kir6.2 (Kir6.2G132S, substitution of glycine with serine at position 132) in pancreatic beta cells [17].
  • Formed through association of the Kir6.2 pore and the sulfonylurea receptor, the stress-responsive ATP-sensitive K(+) channels (K(ATP) channels), with their metabolic-sensing capability and broad tissue expression, are potential candidates for integrating the systemic adaptive response to repetitive exercise [18].
  • The novel diazoxide analog 3-isopropylamino-7-methoxy-4H-1,2,4-benzothiadiazine 1,1-dioxide is a selective Kir6.2/SUR1 channel opener [19].
  • We additionally demonstrated that pyruvate kinase also interacts with Kir6.2 subunits [20].

Regulatory relationships of Kcnj11

  • Here we show evidence for the interaction of H+ with ATP in regulating a cloned K(ATP) channel, i.e. Kir6.2 expressed with and without the SUR1 subunit [21].
  • Kir6.2-deficient mice are susceptible to stimulated ANP secretion: K(ATP) channel acts as a negative feedback mechanism [22]?
  • To examine the role of sarcolemmal K(ATP) channels in cardiac function, we generated transgenic mice expressing GFP-tagged Kir6.2 subunits with reduced ATP sensitivity under control of the cardiac alpha-myosin heavy chain promoter [23].

Other interactions of Kcnj11

  • In contrast to wild-type, surviving dopaminergic SN neurons of homozygous weaver mouse exclusively expressed SUR1 + Kir6.2 during the active period of dopaminergic neurodegeneration [24].
  • In mice lacking K(ATP) channels (Kir6.2(-/-) mice), we found that pretreatment with GIP in vivo failed to blunt the rise in blood glucose levels after oral glucose load [16].
  • Accordingly, disruption of the IRS-1 gene affects neither systemic insulin sensitivity nor glucose uptake in skeletal muscles of Kir6.2-deficient mice [14].
  • METHODS: Double-knockout mice were generated by intercrossing Kir6.2-knockout mice with GIP receptor-knockout mice [15].
  • Kir6.2-SUR2A currents exhibited a single low-affinity site with a Ki of 0.8 +/- 0.1 mmol/l (n = 5), which is likely to reside on the Kir6.2 subunit [25].

Analytical, diagnostic and therapeutic context of Kcnj11

  • Perfusion experiments of Kir6.2(-/-) mice revealed severely impaired potentiation of insulin secretion by 1 nmol/l GIP and substantial potentiation by 1 nmol/l GLP-1 [16].
  • Relative to their corresponding wild type, semi-quantitative immunohistochemistry showed that GLUT4 protein expression as measured by a GLUT4 antibody recognizing an extracellular epitope was increased in the Kir6.2(-/-) K-ATP mice [6].
  • Here, we report the heterologous expression and purification of a functionally active K(ATP) channel complex composed of pore-forming Kir6.2 and regulatory SUR1 subunits, and determination of its structure at 18 A resolution by single-particle electron microscopy [9].
  • The sites of Kir6.2 mRNA expression were determined by in situ hybridization histochemistry with a digoxigenin (DIG)-labeled antisense cRNA probe [26].
  • In situ hybridization and immunofluorescence staining of serial sections with the anti-insulin, the anti-glucagon, and the anti-somatostatin antibodies showed Kir6.2 mRNA to be present in alpha-, beta-, and delta-cells [26].


  1. Hyperinsulinism in mice with heterozygous loss of K(ATP) channels. Remedi, M.S., Rocheleau, J.V., Tong, A., Patton, B.L., McDaniel, M.L., Piston, D.W., Koster, J.C., Nichols, C.G. Diabetologia (2006) [Pubmed]
  2. Protective role of ATP-sensitive potassium channels in hypoxia-induced generalized seizure. Yamada, K., Ji, J.J., Yuan, H., Miki, T., Sato, S., Horimoto, N., Shimizu, T., Seino, S., Inagaki, N. Science (2001) [Pubmed]
  3. ATP-sensitive K+ channels in the hypothalamus are essential for the maintenance of glucose homeostasis. Miki, T., Liss, B., Minami, K., Shiuchi, T., Saraya, A., Kashima, Y., Horiuchi, M., Ashcroft, F., Minokoshi, Y., Roeper, J., Seino, S. Nat. Neurosci. (2001) [Pubmed]
  4. Defective insulin secretion and enhanced insulin action in KATP channel-deficient mice. Miki, T., Nagashima, K., Tashiro, F., Kotake, K., Yoshitomi, H., Tamamoto, A., Gonoi, T., Iwanaga, T., Miyazaki, J., Seino, S. Proc. Natl. Acad. Sci. U.S.A. (1998) [Pubmed]
  5. Kir6.2 is required for adaptation to stress. Zingman, L.V., Hodgson, D.M., Bast, P.H., Kane, G.C., Perez-Terzic, C., Gumina, R.J., Pucar, D., Bienengraeber, M., Dzeja, P.P., Miki, T., Seino, S., Alekseev, A.E., Terzic, A. Proc. Natl. Acad. Sci. U.S.A. (2002) [Pubmed]
  6. Cerebral glucose transporters expression and spatial learning in the K-ATP Kir6.2(-/-) knockout mice. Choeiri, C., Staines, W.A., Miki, T., Seino, S., Renaud, J.M., Teutenberg, K., Messier, C. Behav. Brain Res. (2006) [Pubmed]
  7. Behavioral phenotyping of mice lacking the K ATP channel subunit Kir6.2. Deacon, R.M., Brook, R.C., Meyer, D., Haeckel, O., Ashcroft, F.M., Miki, T., Seino, S., Liss, B. Physiol. Behav. (2006) [Pubmed]
  8. K-ATP channels promote the differential degeneration of dopaminergic midbrain neurons. Liss, B., Haeckel, O., Wildmann, J., Miki, T., Seino, S., Roeper, J. Nat. Neurosci. (2005) [Pubmed]
  9. 3-D structural and functional characterization of the purified KATP channel complex Kir6.2-SUR1. Mikhailov, M.V., Campbell, J.D., de Wet, H., Shimomura, K., Zadek, B., Collins, R.F., Sansom, M.S., Ford, R.C., Ashcroft, F.M. EMBO J. (2005) [Pubmed]
  10. Identification of residues contributing to the ATP binding site of Kir6.2. Trapp, S., Haider, S., Jones, P., Sansom, M.S., Ashcroft, F.M. EMBO J. (2003) [Pubmed]
  11. Intracellular ATP-sensitive K(+) channels in mouse pancreatic beta cells: against a role in organelle cation homeostasis. Varadi, A., Grant, A., McCormack, M., Nicolson, T., Magistri, M., Mitchell, K.J., Halestrap, A.P., Yuan, H., Schwappach, B., Rutter, G.A. Diabetologia (2006) [Pubmed]
  12. Genetic disruption of Kir6.2, the pore-forming subunit of ATP-sensitive K+ channel, predisposes to catecholamine-induced ventricular dysrhythmia. Liu, X.K., Yamada, S., Kane, G.C., Alekseev, A.E., Hodgson, D.M., O'Cochlain, F., Jahangir, A., Miki, T., Seino, S., Terzic, A. Diabetes (2004) [Pubmed]
  13. Mutations in the linker domain of NBD2 of SUR inhibit transduction but not nucleotide binding. Matsuo, M., Dabrowski, M., Ueda, K., Ashcroft, F.M. EMBO J. (2002) [Pubmed]
  14. ATP-sensitive K+ channel-mediated glucose uptake is independent of IRS-1/phosphatidylinositol 3-kinase signaling. Minami, K., Morita, M., Saraya, A., Yano, H., Terauchi, Y., Miki, T., Kuriyama, T., Kadowaki, T., Seino, S. Am. J. Physiol. Endocrinol. Metab. (2003) [Pubmed]
  15. Gastric inhibitory polypeptide is the major insulinotropic factor in K(ATP) null mice. Tsukiyama, K., Yamada, Y., Miyawaki, K., Hamasaki, A., Nagashima, K., Hosokawa, M., Fujimoto, S., Takahashi, A., Toyoda, K., Toyokuni, S., Oiso, Y., Seino, Y. Eur. J. Endocrinol. (2004) [Pubmed]
  16. Distinct effects of glucose-dependent insulinotropic polypeptide and glucagon-like peptide-1 on insulin secretion and gut motility. Miki, T., Minami, K., Shinozaki, H., Matsumura, K., Saraya, A., Ikeda, H., Yamada, Y., Holst, J.J., Seino, S. Diabetes (2005) [Pubmed]
  17. Abnormalities of pancreatic islets by targeted expression of a dominant-negative KATP channel. Miki, T., Tashiro, F., Iwanaga, T., Nagashima, K., Yoshitomi, H., Aihara, H., Nitta, Y., Gonoi, T., Inagaki, N., Miyazaki, J., Seino, S. Proc. Natl. Acad. Sci. U.S.A. (1997) [Pubmed]
  18. ATP-sensitive K+ channel knockout compromises the metabolic benefit of exercise training, resulting in cardiac deficits. Kane, G.C., Behfar, A., Yamada, S., Perez-Terzic, C., O'Cochlain, F., Reyes, S., Dzeja, P.P., Miki, T., Seino, S., Terzic, A. Diabetes (2004) [Pubmed]
  19. The novel diazoxide analog 3-isopropylamino-7-methoxy-4H-1,2,4-benzothiadiazine 1,1-dioxide is a selective Kir6.2/SUR1 channel opener. Dabrowski, M., Ashcroft, F.M., Ashfield, R., Lebrun, P., Pirotte, B., Egebjerg, J., Bondo Hansen, J., Wahl, P. Diabetes (2002) [Pubmed]
  20. The glycolytic enzymes, glyceraldehyde-3-phosphate dehydrogenase, triose-phosphate isomerase, and pyruvate kinase are components of the K(ATP) channel macromolecular complex and regulate its function. Dhar-Chowdhury, P., Harrell, M.D., Han, S.Y., Jankowska, D., Parachuru, L., Morrissey, A., Srivastava, S., Liu, W., Malester, B., Yoshida, H., Coetzee, W.A. J. Biol. Chem. (2005) [Pubmed]
  21. Allosteric modulation of the mouse Kir6.2 channel by intracellular H+ and ATP. Wu, J., Cui, N., Piao, H., Wang, Y., Xu, H., Mao, J., Jiang, C. J. Physiol. (Lond.) (2002) [Pubmed]
  22. Kir6.2-deficient mice are susceptible to stimulated ANP secretion: K(ATP) channel acts as a negative feedback mechanism? Saegusa, N., Sato, T., Saito, T., Tamagawa, M., Komuro, I., Nakaya, H. Cardiovasc. Res. (2005) [Pubmed]
  23. Tolerance for ATP-insensitive K(ATP) channels in transgenic mice. Koster, J.C., Knopp, A., Flagg, T.P., Markova, K.P., Sha, Q., Enkvetchakul, D., Betsuyaku, T., Yamada, K.A., Nichols, C.G. Circ. Res. (2001) [Pubmed]
  24. Alternative sulfonylurea receptor expression defines metabolic sensitivity of K-ATP channels in dopaminergic midbrain neurons. Liss, B., Bruns, R., Roeper, J. EMBO J. (1999) [Pubmed]
  25. Differential sensitivity of beta-cell and extrapancreatic K(ATP) channels to gliclazide. Gribble, F.M., Ashcroft, F.M. Diabetologia (1999) [Pubmed]
  26. Localization of the ATP-sensitive K+ channel subunit Kir6.2 in mouse pancreas. Suzuki, M., Fujikura, K., Inagaki, N., Seino, S., Takata, K. Diabetes (1997) [Pubmed]
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