Genomes and Genes
Gene Symbol: Kcnj11
Description: potassium inwardly rectifying channel, subfamily J, member 11
Alias: Kir6.2, mBIR, ATP-sensitive inward rectifier potassium channel 11, inward rectifier K(+) channel Kir6.2
- Sakura H, Ammala C, Smith P, Gribble F, Ashcroft F. Cloning and functional expression of the cDNA encoding a novel ATP-sensitive potassium channel subunit expressed in pancreatic beta-cells, brain, heart and skeletal muscle. FEBS Lett. 1995;377:338-44 pubmed..Single-channel activity was voltage-independent and was blocked by 1 mM intracellular ATP or 0.5 mM tolbutamide. We conclude that the Kir6.2/SUR channel complex comprises the ATP-sensitive K-channel...
- Yang Z, Chen J, Ni M, Zhao T, Deng Y, Tao X, et al. Role of Kir6.2 subunits of ATP-sensitive potassium channels in endotoxemia-induced cardiac dysfunction. Cardiovasc Diabetol. 2013;12:75 pubmed publisher..ATP-sensitive potassium (KATP) channels are critical to cardiac function. This study investigates the role of Kir6.2 subunits of KATP channels on cardiac dysfunction in lipopolysaccharide (LPS)-induced endotoxemia...
- Wojtovich A, Urciuoli W, Chatterjee S, Fisher A, Nehrke K, Brookes P. Kir6.2 is not the mitochondrial KATP channel but is required for cardioprotection by ischemic preconditioning. Am J Physiol Heart Circ Physiol. 2013;304:H1439-45 pubmed publisher..2(-/-) mice, suggesting no role for Kir6.2 in the mKATP. Collectively, these data indicate that Kir6.2 is required for the full response to IPC or diazoxide but is not involved in mKATP formation. ..
- Girard C, Wunderlich F, Shimomura K, Collins S, Kaizik S, Proks P, et al. Expression of an activating mutation in the gene encoding the KATP channel subunit Kir6.2 in mouse pancreatic beta cells recapitulates neonatal diabetes. J Clin Invest. 2009;119:80-90 pubmed publisher..2, SUR1, and insulin mRNA. All these changes are expected to contribute to the diabetes of beta-V59M mice. Their cause requires further investigation. ..
- MacDonald P, De Marinis Y, Ramracheya R, Salehi A, Ma X, Johnson P, et al. A K ATP channel-dependent pathway within alpha cells regulates glucagon release from both rodent and human islets of Langerhans. PLoS Biol. 2007;5:e143 pubmed..We propose that elevated glucose reduces electrical activity and exocytosis via depolarisation-induced inactivation of ion channels involved in action potential firing and secretion. ..
- Mikhailov M, Campbell J, de Wet H, Shimomura K, Zadek B, Collins R, et al. 3-D structural and functional characterization of the purified KATP channel complex Kir6.2-SUR1. EMBO J. 2005;24:4166-75 pubmed..2. The nucleotide-binding domains of adjacent SUR1 appear to interact, and form a large docking platform for cytosolic proteins. The structure, in combination with molecular modelling, suggests how SUR1 interacts with Kir6.2...
- Liu X, Yamada S, Kane G, Alekseev A, Hodgson D, O Cochlain F, et al. Genetic disruption of Kir6.2, the pore-forming subunit of ATP-sensitive K+ channel, predisposes to catecholamine-induced ventricular dysrhythmia. Diabetes. 2004;53 Suppl 3:S165-8 pubmed..Thus, intact KATP channel function is mandatory for adequate repolarization under sympathetic stress providing electrical tolerance against triggered arrhythmia. ..
- Lorenz E, Alekseev A, Krapivinsky G, Carrasco A, Clapham D, Terzic A. Evidence for direct physical association between a K+ channel (Kir6.2) and an ATP-binding cassette protein (SUR1) which affects cellular distribution and kinetic behavior of an ATP-sensitive K+ channel. Mol Cell Biol. 1998;18:1652-9 pubmed..This study provides direct evidence that an inwardly rectifying K+ channel and an ATP-binding cassette protein physically associate, which affects the cellular distribution and kinetic behavior of a KATP channel...
- Yamada M, Isomoto S, Matsumoto S, Kondo C, Shindo T, Horio Y, et al. Sulphonylurea receptor 2B and Kir6.1 form a sulphonylurea-sensitive but ATP-insensitive K+ channel. J Physiol. 1997;499 ( Pt 3):715-20 pubmed..5. Therefore, the K+ channel composed of SUR2B and Kir6.1 is not a classical ATP-sensitive K+ channel but closely resembles the nucleotide diphosphate-dependent K+ channel in vascular smooth muscle cells...
- Liss B, Bruns R, Roeper J. Alternative sulfonylurea receptor expression defines metabolic sensitivity of K-ATP channels in dopaminergic midbrain neurons. EMBO J. 1999;18:833-46 pubmed
- Haider S, Grottesi A, Hall B, Ashcroft F, Sansom M. Conformational dynamics of the ligand-binding domain of inward rectifier K channels as revealed by molecular dynamics simulations: toward an understanding of Kir channel gating. Biophys J. 2005;88:3310-20 pubmed..It is of interest that loss of exact rotational symmetry has also been suggested to play a role in gating in the bacterial Kir homolog, KirBac1.1, and in the nicotinic acetylcholine receptor channel. ..
- Tong X, Porter L, Liu G, Dhar Chowdhury P, Srivastava S, Pountney D, et al. Consequences of cardiac myocyte-specific ablation of KATP channels in transgenic mice expressing dominant negative Kir6 subunits. Am J Physiol Heart Circ Physiol. 2006;291:H543-51 pubmed
- John S, Weiss J, Xie L, Ribalet B. Molecular mechanism for ATP-dependent closure of the K+ channel Kir6.2. J Physiol. 2003;552:23-34 pubmed..Binding of the alpha phosphate group of ATP to R201 then stabilizes the closed state. R50 on the N-terminus controls ATP binding by facilitating the interaction of the beta phosphate group of ATP with K185 to destabilize the open state...
- Gumina R, Pucar D, Bast P, Hodgson D, Kurtz C, Dzeja P, et al. Knockout of Kir6.2 negates ischemic preconditioning-induced protection of myocardial energetics. Am J Physiol Heart Circ Physiol. 2003;284:H2106-13 pubmed..Thus intact K(ATP) channels are integral in ischemic preconditioning-induced protection of cellular energetic dynamics and associated cardiac performance. ..
- Zingman L, Hodgson D, Bast P, Kane G, Perez Terzic C, Gumina R, et al. Kir6.2 is required for adaptation to stress. Proc Natl Acad Sci U S A. 2002;99:13278-83 pubmed..In the absence of Kir6.2, vigorous sympathetic challenge caused arrhythmia and sudden death, preventable by calcium-channel blockade. Thus, this vital function identifies a physiological role for K(ATP) channels in the heart. ..
- Suzuki M, Fujikura K, Inagaki N, Seino S, Takata K. Localization of the ATP-sensitive K+ channel subunit Kir6.2 in mouse pancreas. Diabetes. 1997;46:1440-4 pubmed..2 is at the plasma membrane of islet cells. These results suggest that Kir6.2, as a component of K(ATP) channels, is an important molecule in the regulation of all the release of insulin, glucagon, and somatostatin. ..
- Yamada K, Ji J, Yuan H, Miki T, Sato S, Horimoto N, et al. Protective role of ATP-sensitive potassium channels in hypoxia-induced generalized seizure. Science. 2001;292:1543-6 pubmed..K(ATP) channels exert a depressant effect on SNr neuronal activity during hypoxia and may be involved in the nigral protection mechanism against generalized seizures. ..
- Suzuki M, Li R, Miki T, Uemura H, Sakamoto N, Ohmoto Sekine Y, et al. Functional roles of cardiac and vascular ATP-sensitive potassium channels clarified by Kir6.2-knockout mice. Circ Res. 2001;88:570-7 pubmed..1 mRNA was expressed. These findings indicate that the Kir6.2 subunit mediates the depression of cardiac excitability and contractility induced by KCOs; in contrast, Kir6.2 plays no discernible role in the arterial tree. ..
- Arrell D, Zlatkovic J, Kane G, Yamada S, Terzic A. ATP-sensitive K+ channel knockout induces cardiac proteome remodeling predictive of heart disease susceptibility. J Proteome Res. 2009;8:4823-34 pubmed publisher..Proteomic cartography thus provides an integral view of molecular remodeling in the heart induced by K(ATP) channel deletion, establishing a systems approach that predicts outcome at a presymptomatic stage. ..
- Trapp S, Haider S, Jones P, Sansom M, Ashcroft F. Identification of residues contributing to the ATP binding site of Kir6.2. EMBO J. 2003;22:2903-12 pubmed..These results support the idea that K185 interacts with the beta-phosphate of ATP. Thus both N- and C-termini may contribute to the ATP binding site. ..
- Liss B, Haeckel O, Wildmann J, Miki T, Seino S, Roeper J. K-ATP channels promote the differential degeneration of dopaminergic midbrain neurons. Nat Neurosci. 2005;8:1742-51 pubmed..Thus, K-ATP channel activation has an unexpected role in promoting death of DA neurons in chronic disease. ..
- Miki T, Nagashima K, Tashiro F, Kotake K, Yoshitomi H, Tamamoto A, et al. Defective insulin secretion and enhanced insulin action in KATP channel-deficient mice. Proc Natl Acad Sci U S A. 1998;95:10402-6 pubmed
- Antcliff J, Haider S, Proks P, Sansom M, Ashcroft F. Functional analysis of a structural model of the ATP-binding site of the KATP channel Kir6.2 subunit. EMBO J. 2005;24:229-39 pubmed..Consistent with a role in gating, mutations in the slide helix bias the intrinsic channel conformation towards the open state. ..
- Inagaki N, Gonoi T, Clement J, Namba N, Inazawa J, Gonzalez G, et al. Reconstitution of IKATP: an inward rectifier subunit plus the sulfonylurea receptor. Science. 1995;270:1166-70 pubmed..Gene mapping data show that these two potassium channel subunit genes are clustered on human chromosome 11 at position 11p15.1...
- Shiota C, Rocheleau J, Shiota M, Piston D, Magnuson M. Impaired glucagon secretory responses in mice lacking the type 1 sulfonylurea receptor. Am J Physiol Endocrinol Metab. 2005;289:E570-7 pubmed..These findings indicate that K(ATP) channels in alpha-cells play a key role in regulating glucagon secretion, thereby adding to the paradox of how mice that lack K(ATP) channels maintain euglycemia...
- Gong B, Miki T, Seino S, Renaud J. A K(ATP) channel deficiency affects resting tension, not contractile force, during fatigue in skeletal muscle. Am J Physiol Cell Physiol. 2000;279:C1351-8 pubmed..It is also suggested that the K(ATP) channel plays an important role in protecting muscle function in older mice...
- Suzuki M, Sasaki N, Miki T, Sakamoto N, Ohmoto Sekine Y, Tamagawa M, et al. Role of sarcolemmal K(ATP) channels in cardioprotection against ischemia/reperfusion injury in mice. J Clin Invest. 2002;109:509-16 pubmed..The rapid heart rate of the mouse (>600 beats per minute) may magnify the relative importance of sarcK(ATP) channels during ischemia, prompting caution in the extrapolation of the conclusions to larger mammals. ..
- Quwailid M, Hugill A, Dear N, Vizor L, Wells S, Horner E, et al. A gene-driven ENU-based approach to generating an allelic series in any gene. Mamm Genome. 2004;15:585-91 pubmed..It is now available to academic collaborators as a community resource. ..
- Miki T, Liss B, Minami K, Shiuchi T, Saraya A, Kashima Y, et al. ATP-sensitive K+ channels in the hypothalamus are essential for the maintenance of glucose homeostasis. Nat Neurosci. 2001;4:507-12 pubmed..Thus, our results demonstrate that KATP channels are important in glucose sensing in VMH GR neurons, and are essential for the maintenance of glucose homeostasis...
- Inagaki N, Gonoi T, Clement J, Wang C, Aguilar Bryan L, Bryan J, et al. A family of sulfonylurea receptors determines the pharmacological properties of ATP-sensitive K+ channels. Neuron. 1996;16:1011-7 pubmed..The present study shows that the ATP sensitivity and pharmacological properties of K(ATP) channels are determined by a family of structurally related but functionally distinct sulfonylurea receptors...
- Kane G, Behfar A, Yamada S, Perez Terzic C, O Cochlain F, Reyes S, et al. ATP-sensitive K+ channel knockout compromises the metabolic benefit of exercise training, resulting in cardiac deficits. Diabetes. 2004;53 Suppl 3:S169-75 pubmed..Thus, Kir6.2-containing K(ATP) channel activity is required for attainment of the physiologic benefits of exercise training without injury. ..
- Yamada S, Kane G, Behfar A, Liu X, Dyer R, Faustino R, et al. Protection conferred by myocardial ATP-sensitive K+ channels in pressure overload-induced congestive heart failure revealed in KCNJ11 Kir6.2-null mutant. J Physiol. 2006;577:1053-65 pubmed..Thus, K(ATP) channels appear mandatory in acute and chronic cardiac adaptation to imposed haemodynamic load, protecting against congestive heart failure and death. ..
- Kane G, Behfar A, Dyer R, O Cochlain D, Liu X, Hodgson D, et al. KCNJ11 gene knockout of the Kir6.2 KATP channel causes maladaptive remodeling and heart failure in hypertension. Hum Mol Genet. 2006;15:2285-97 pubmed..Here in experimental hypertension, knockout of the KCNJ11 gene, encoding the Kir6...
- Choi S, Yeum C, Chang I, You H, Park J, Jeong H, et al. Activating of ATP-dependent K+ channels comprised of K(ir) 6.2 and SUR 2B by PGE2 through EP2 receptor in cultured interstitial cells of Cajal from murine small intestine. Cell Physiol Biochem. 2006;18:187-98 pubmed..2-SUR 2B in ICC and this action of PGE(2) are through EP(2) receptor subtype and also the activation of ATP-dependent K(+) channels involves intracellular Ca(2+) mobilization...
- Li X, Rapedius M, Baukrowitz T, Liu G, Srivastava D, Daut J, et al. 5-Hydroxydecanoate and coenzyme A are inhibitors of native sarcolemmal KATP channels in inside-out patches. Biochim Biophys Acta. 2010;1800:385-91 pubmed publisher..However, in intact cells, 5-HD fails to inhibit sarcK(ATP) channels, suggesting that mitochondria are the preconditioning-relevant targets of 5-HD. ..
- Sierra A, Zhu Z, Sapay N, Sharotri V, Kline C, Luczak E, et al. Regulation of cardiac ATP-sensitive potassium channel surface expression by calcium/calmodulin-dependent protein kinase II. J Biol Chem. 2013;288:1568-81 pubmed publisher..This mechanism couples the surface expression of cardiac K(ATP) channels with calcium signaling and reveals new targets to improve cardiac energy efficiency and stress resistance. ..
- Mankouri J, Taneja T, Smith A, Ponnambalam S, Sivaprasadarao A. Kir6.2 mutations causing neonatal diabetes prevent endocytosis of ATP-sensitive potassium channels. EMBO J. 2006;25:4142-51 pubmed..The data imply that endocytosis of KATP channels plays a crucial role in the (patho)-physiology of insulin secretion...
- Deacon R, Brook R, Meyer D, Haeckel O, Ashcroft F, Miki T, et al. Behavioral phenotyping of mice lacking the K ATP channel subunit Kir6.2. Physiol Behav. 2006;87:723-33 pubmed..However, according to the widespread expression of K(ATP) channels, these effects are complex, being dependent on details of test apparatus, procedure and prior experience. ..
- Matsuzaki I, Chatterjee S, Debolt K, Manevich Y, Zhang Q, Fisher A. Membrane depolarization and NADPH oxidase activation in aortic endothelium during ischemia reflect altered mechanotransduction. Am J Physiol Heart Circ Physiol. 2005;288:H336-43 pubmed
- Bushman J, Gay J, Tewson P, Stanley C, Shyng S. Characterization and functional restoration of a potassium channel Kir6.2 pore mutation identified in congenital hyperinsulinism. J Biol Chem. 2010;285:6012-23 pubmed publisher..We conclude that the glycine at 156 is not essential for K(ATP) channel gating and that the Kir6.2 gating defect caused by the G156R mutation could be rescued by manipulating chemical interactions between pore residues. ..
- Fukuzaki K, Sato T, Miki T, Seino S, Nakaya H. Role of sarcolemmal ATP-sensitive K+ channels in the regulation of sinoatrial node automaticity: an evaluation using Kir6.2-deficient mice. J Physiol. 2008;586:2767-78 pubmed publisher..In conclusion, the present study using Kir6.2 KO mice indicates that, during hypoxia, activation of sarcolemmal K(ATP) channels in SAN cells inhibits SAN automaticity, which is important for the protection of SAN cells. ..
- Clark R, Mannikko R, Stuckey D, Iberl M, Clarke K, Ashcroft F. Mice expressing a human K(ATP) channel mutation have altered channel ATP sensitivity but no cardiac abnormalities. Diabetologia. 2012;55:1195-204 pubmed publisher..This may have implications for the choice of sulfonylurea used to treat neonatal diabetes. ..
- Miki T, Iwanaga T, Nagashima K, Ihara Y, Seino S. Roles of ATP-sensitive K+ channels in cell survival and differentiation in the endocrine pancreas. Diabetes. 2001;50 Suppl 1:S48-51 pubmed..2G372S Tg and Kir6.2-/- mice compared with the respective controls. Thus, studies of Kir6.2G372S Tg and Kir6.2-/- mice indicate that K(ATP) channels play an important role in cell survival and differentiation in the endocrine pancreas. ..
- Winarto A, Miki T, Seino S, Iwanaga T. Morphological changes in pancreatic islets of KATP channel-deficient mice: the involvement of KATP channels in the survival of insulin cells and the maintenance of islet architecture. Arch Histol Cytol. 2001;64:59-67 pubmed..These findings suggest that the KATP channel is important for insulin cell survival and also regulates the differentiation of islet cells. ..
- Xiang L, Hester R. Adipocyte-derived factor reduces vasodilatory capability in ob-/ob- mice. Am J Physiol Heart Circ Physiol. 2009;297:H689-95 pubmed publisher..The absolute diameters induced by muscle stimulation were not altered by the fat-conditioned PSS. These results suggest that, in ob mice, local ADFs reduce the functional vasodilatory capability via opening K(ATP) channels. ..
- Fioramonti X, Lorsignol A, Taupignon A, Penicaud L. A new ATP-sensitive K+ channel-independent mechanism is involved in glucose-excited neurons of mouse arcuate nucleus. Diabetes. 2004;53:2767-75 pubmed..Moreover, HGE neurons were also present in ARC of Kir6.2 null mice. These results suggested that ARC neurons have the ability to sense higher glucose concentrations than 5 mmol/l through a new K(ATP) channel-independent mechanism. ..
- Milovanova T, Chatterjee S, Hawkins B, Hong N, Sorokina E, Debolt K, et al. Caveolae are an essential component of the pathway for endothelial cell signaling associated with abrupt reduction of shear stress. Biochim Biophys Acta. 2008;1783:1866-75 pubmed publisher..These studies indicate that caveolin-1 functions as a shear sensor in flow-adapted EC resulting in ROS-mediated cell signaling and endothelial cell proliferation following the abrupt reduction in flow. ..
- Lybaert P, Vanbellinghen A, Quertinmont E, Petein M, Meuris S, Lebrun P. KATP channel subunits are expressed in the epididymal epithelium in several mammalian species. Biol Reprod. 2008;79:253-61 pubmed publisher..Immunohistochemical, Western blot, and RT-PCR techniques were used. A positive immunostaining for Kir6.2 (KCNJ11) and SUR2 (ABCC9) was observed by immunoenzymatic and immunofluorescent approaches in the principal epithelial ..
- Reyes S, Kane G, Miki T, Seino S, Terzic A. KATP channels confer survival advantage in cocaine overdose. Mol Psychiatry. 2007;12:1060-1 pubmed
- Koster J, Remedi M, Masia R, Patton B, Tong A, Nichols C. Expression of ATP-insensitive KATP channels in pancreatic beta-cells underlies a spectrum of diabetic phenotypes. Diabetes. 2006;55:2957-64 pubmed..The data demonstrate that a range of phenotypes can be expected for a reduction in ATP sensitivity of beta-cell K(ATP) channels and provide models for the corollary neonatal diabetes in humans. ..
- Tarasov A, Girard C, Ashcroft F. ATP sensitivity of the ATP-sensitive K+ channel in intact and permeabilized pancreatic beta-cells. Diabetes. 2006;55:2446-54 pubmed..The ATP sensitivity observed in permeabilized cells accounts quantitatively for K(ATP) channel activity in intact cells. Thus, our results show that the principal metabolic regulators of K(ATP) channel activity are MgATP and MgADP...
- Pu J, Ye B, Kroboth S, McNally E, Makielski J, Shi N. Cardiac sulfonylurea receptor short form-based channels confer a glibenclamide-insensitive KATP activity. J Mol Cell Cardiol. 2008;44:188-200 pubmed..1 or Kir6.2 suggesting that the short forms may function as hemi-transporters reported in other eukaryotic ABC transporter subgroups. Our results indicate that different K(ATP) compositions may co-exist in cardiac sarcolemmal membrane...
- Wang R, Su J, Zhang X, Shi Y, Cui N, Onyebuchi V, et al. Kir6.2 channel gating by intracellular protons: subunit stoichiometry for ligand binding and channel gating. J Membr Biol. 2006;213:155-64 pubmed
- Aziz Q, Thomas A, Khambra T, Tinker A. Regulation of the ATP-sensitive potassium channel subunit, Kir6.2, by a Ca2+-dependent protein kinase C. J Biol Chem. 2012;287:6196-207 pubmed publisher..2 (Ser-372) whose phosphorylation leads to down-regulation of the channel complex. This inhibitory effect is distinct from activation which is seen with low levels of channel activity...
- Varadi A, Grant A, McCormack M, Nicolson T, Magistri M, Mitchell K, et al. Intracellular ATP-sensitive K+ channels in mouse pancreatic beta cells: against a role in organelle cation homeostasis. Diabetologia. 2006;49:1567-77 pubmed..The aim of this study was to explore these possibilities and to test the hypothesis that vesicle-resident channels play a role in the control of organellar Ca(2+) concentration or pH...
- Minami K, Morita M, Saraya A, Yano H, Terauchi Y, Miki T, et al. ATP-sensitive K+ channel-mediated glucose uptake is independent of IRS-1/phosphatidylinositol 3-kinase signaling. Am J Physiol Endocrinol Metab. 2003;285:E1289-96 pubmed..2 gene. Disruption of Kir6.2-containing Katp channels clearly protects against IRS-1-associated insulin resistance by increasing glucose uptake in skeletal muscles by a mechanism separate from the IRS-1/PI3K pathway. ..
- Li R, Leppo M, Miki T, Seino S, Marban E. Molecular basis of electrocardiographic ST-segment elevation. Circ Res. 2000;87:837-9 pubmed..Thus, the opening of sarcolemmal K(ATP)channels underlies ST elevation during ischemia. These data are the first to link a specific gene product with a common electrocardiographic phenomenon. ..
- Nelson T, Martinez Fernandez A, Terzic A. KCNJ11 knockout morula re-engineered by stem cell diploid aggregation. Philos Trans R Soc Lond B Biol Sci. 2009;364:269-76 pubmed publisherb>KCNJ11-encoded Kir6.2 assembles with ATP-binding cassette sulphonylurea receptors to generate ATP-sensitive K+ (KATP) channel complexes...