Gene Symbol: Kcnj8
Description: potassium voltage-gated channel subfamily J member 8
Alias: Kir6.1, UKATP1, uKATP-1, ATP-sensitive inward rectifier potassium channel 8, Inwardly rectifying potassium channel gene, subfamily J-8 (ATP sensitive), inward rectifier K(+) channel Kir6.1, inwardly rectifier K(+) channel Kir6.1, potassium channel, inwardly rectifying subfamily J member 8, potassium inwardly-rectifying channel, subfamily J, member 8
Species: rat
Products:     Kcnj8

Top Publications

  1. Akao M, Otani H, Horie M, Takano M, Kuniyasu A, Nakayama H, et al. Myocardial ischemia induces differential regulation of KATP channel gene expression in rat hearts. J Clin Invest. 1997;100:3053-9 pubmed
    ..2-fold) region of rat hearts subjected to 60 min of ischemia followed by 24 h of reperfusion. Thus, prolonged myocardial ischemia rather than reperfusion induces delayed and differential regulation of cardiac KATP channel gene expression...
  2. Medeiros Domingo A, Tan B, Crotti L, Tester D, Eckhardt L, Cuoretti A, et al. Gain-of-function mutation S422L in the KCNJ8-encoded cardiac K(ATP) channel Kir6.1 as a pathogenic substrate for J-wave syndromes. Heart Rhythm. 2010;7:1466-71 pubmed publisher
    ..b>KCNJ8, which encodes the cardiac K(ATP) Kir6...
  3. Malester B, Tong X, Ghiu I, Kontogeorgis A, Gutstein D, Xu J, et al. Transgenic expression of a dominant negative K(ATP) channel subunit in the mouse endothelium: effects on coronary flow and endothelin-1 secretion. FASEB J. 2007;21:2162-72 pubmed
    ..These data are consistent with a role for endothelial K(ATP) channels to control the coronary blood flow by modulating the release of the vasoconstrictor, endothelin-1. ..
  4. van Bever L, Poitry S, Faure C, Norman R, Roatti A, Baertschi A. Pore loop-mutated rat KIR6.1 and KIR6.2 suppress KATP current in rat cardiomyocytes. Am J Physiol Heart Circ Physiol. 2004;287:H850-9 pubmed
    ..x trafficking to the sarcolemma. The results favor the view that KIR6.1 may associate with KIR6.2 to form heterotetrameric pores of native K(ATP) channels in cardiomyocytes. ..
  5. Li L, Wu J, Jiang C. Differential expression of Kir6.1 and SUR2B mRNAs in the vasculature of various tissues in rats. J Membr Biol. 2003;196:61-9 pubmed
    ..With their strong expression in small arteries and capillaries, it is very likely that the Kir6.1 and SUR2B form the vascular isoform of K(ATP) channels in these vasculatures...
  6. Miki T, Suzuki M, Shibasaki T, Uemura H, Sato T, Yamaguchi K, et al. Mouse model of Prinzmetal angina by disruption of the inward rectifier Kir6.1. Nat Med. 2002;8:466-72 pubmed
    ..We report here that mice lacking the gene encoding Kir6.1 (known as Kcnj8) have a high rate of sudden death associated with spontaneous ST elevation followed by atrioventricular block as ..
  7. Shi W, Cui N, Wu Z, Yang Y, Zhang S, Gai H, et al. Lipopolysaccharides up-regulate Kir6.1/SUR2B channel expression and enhance vascular KATP channel activity via NF-kappaB-dependent signaling. J Biol Chem. 2010;285:3021-9 pubmed publisher
    ..1 and SUR2B expression to a similar degree as LPS. Thus, the effect of LPS on vasodilation involves up-regulation of K(ATP) channel expression, in which the NF-kappaB-dependent signaling plays an important role. ..
  8. Yang Y, Shi W, Chen X, Cui N, Konduru A, Shi Y, et al. Molecular basis and structural insight of vascular K(ATP) channel gating by S-glutathionylation. J Biol Chem. 2011;286:9298-307 pubmed publisher
    ..This prevented the inner transmembrane helix from undergoing conformational changes necessary for channel gating, retaining the channel in its closed state. ..
  9. Hong M, Kefaloyianni E, Bao L, Malester B, Delaroche D, Neubert T, et al. Cardiac ATP-sensitive K+ channel associates with the glycolytic enzyme complex. FASEB J. 2011;25:2456-67 pubmed publisher
    ..Overall, our data demonstrate close physical association and functional interaction of the glycolytic process (particularly the distal ATP-generating steps) with cardiac K(ATP) channels...

More Information


  1. Nakagawa Y, Yoshioka M, Abe Y, Uchinami H, Ohba T, Ono K, et al. Enhancement of liver regeneration by adenosine triphosphate-sensitive K? channel opener (diazoxide) after partial hepatectomy. Transplantation. 2012;93:1094-100 pubmed publisher
    ..We investigated the KATP channel in hepatocytes and examined the effects of diazoxide, a potent KATP channel opener, on liver regeneration using a rat model...
  2. Jöns T, Wittschieber D, Beyer A, Meier C, Brune A, Thomzig A, et al. K+-ATP-channel-related protein complexes: potential transducers in the regulation of epithelial tight junction permeability. J Cell Sci. 2006;119:3087-97 pubmed
    ..The data presented here shed new light on the physiological and pathophysiological role K(+)-ATP channels might have for the regulation of tight junctions...
  3. Morrissey A, Parachuru L, Leung M, Lopez G, Nakamura T, Tong X, et al. Expression of ATP-sensitive K+ channel subunits during perinatal maturation in the mouse heart. Pediatr Res. 2005;58:185-92 pubmed
    ..Our data suggest that the K(ATP) channel composition may change during maturation, which has important implications for K(ATP) channel function in the developing heart...
  4. Sgard F, Faure C, Drieu la Rochelle C, Graham D, O Connor S, Janiak P, et al. Regulation of ATP-sensitive potassium channel mRNA expression in rat kidney following ischemic injury. Biochem Biophys Res Commun. 2000;269:618-22 pubmed
    ..In contrast, a strong increase in mRNA expression was observed for Kir6.1 shortly (2-6 h) after ischemia. Thus, renal ischemia followed by reperfusion provokes differential regulation of K(ATP) channel gene expression. ..
  5. Light P, Kanji H, Fox J, French R. Distinct myoprotective roles of cardiac sarcolemmal and mitochondrial KATP channels during metabolic inhibition and recovery. FASEB J. 2001;15:2586-94 pubmed
    ..Our data suggest that sarc and mitoKATP channel populations play distinct protective roles, triggered by PKC and/or adenosine, during chemically induced hypoxia/reoxygenation...
  6. Braun G, Veh R, Segerer S, Horster M, Huber S. Developmental expression and functional significance of Kir channel subunits in ureteric bud and nephron epithelia. Pflugers Arch. 2002;445:321-30 pubmed
    ..In summary, Kir6.1/SUR2 channel subunits are highly expressed during early development of ureteric bud and nephron epithelia where Kir6.1/SUR2 activity regulates cell proliferation. ..
  7. Li A, Knutsen R, Zhang H, Osei Owusu P, Moreno Dominguez A, Harter T, et al. Hypotension due to Kir6.1 gain-of-function in vascular smooth muscle. J Am Heart Assoc. 2013;2:e000365 pubmed publisher
    ..We predict that gain of vascular KATP function in humans would lead to a chronic vasodilatory phenotype, as indeed has recently been demonstrated in Cantu syndrome. ..
  8. Lawrence K, Chanalaris A, Scarabelli T, Hubank M, Pasini E, Townsend P, et al. K(ATP) channel gene expression is induced by urocortin and mediates its cardioprotective effect. Circulation. 2002;106:1556-62 pubmed
  9. Liu X, Duan P, Hu X, Li R, Zhu Q. Altered KATP Channel Subunits Expression and Vascular Reactivity in Spontaneously Hypertensive Rats With Age. J Cardiovasc Pharmacol. 2016;68:143-9 pubmed publisher
    ..This study suggests that KATP channels in VSM subunits Kir6.1 and SUR2B contribute to modify the functionality of this channel in hypertension with age. ..
  10. Emanuele E, Falcone C, Carabela M, Minoretti P, D Angelo A, Montagna L, et al. Absence of Kir6.1/KCNJ8 mutations in Italian patients with abnormal coronary vasomotion. Int J Mol Med. 2003;12:509-12 pubmed
    ..A mouse model of human variant (vasospastic) angina has been recently obtained by disruption of Kir6.1/Kcnj8, a gene coding for a small pore-forming inward rectifier potassium channel...
  11. Chen F, Zhang N, Liu P, Zhang Y, Han X, Cai J. [Effects of Guanxinkang on expressions of ATP-sensitive potassium channel subunits Kir6.1, Kir6.2, SUR2A and SUR2B in ischemic myocytes of rats]. Zhong Xi Yi Jie He Xue Bao. 2010;8:458-64 pubmed
  12. 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. ..
  13. Duan X, Guo R, Liu S, Xiao L, Xue H, Guo Q, et al. Gene transfer of cystathionine β-synthase into RVLM increases hydrogen sulfide-mediated suppression of sympathetic outflow via KATP channel in normotensive rats. Am J Physiol Heart Circ Physiol. 2015;308:H603-11 pubmed publisher
    ..1 in AdCBS-injected rats. These results suggest that the increase in KATP channels in the RVLM may be responsible for the greater sympathetic outflow and pressor effect of HA in AdCBS-injected rats compared with AdEGFP-injected rats. ..
  14. Wang J, Li Z, Feng M, Ren K, Shen G, Zhao C, et al. Opening of astrocytic mitochondrial ATP-sensitive potassium channels upregulates electrical coupling between hippocampal astrocytes in rat brain slices. PLoS ONE. 2013;8:e56605 pubmed publisher
    ..In addition, this effect is mainly via up-regulation of the Connexin43-constituted gap junction coupling by an ERK-dependent mechanism in the mitochondria. ..
  15. Wu X, Liu W, Liu Y, Huang Z, Zhang Y, Song X. Reopening of ATP-sensitive potassium channels reduces neuropathic pain and regulates astroglial gap junctions in the rat spinal cord. Pain. 2011;152:2605-15 pubmed publisher
    ..This study may provide a new strategy for treating neuropathic pain using K(ATP) channel openers in the clinic...
  16. Thomzig A, Prüss H, Veh R. The Kir6.1-protein, a pore-forming subunit of ATP-sensitive potassium channels, is prominently expressed by giant cholinergic interneurons in the striatum of the rat brain. Brain Res. 2003;986:132-8 pubmed
    ..A selective modulation of the Kir6.1 subunit in the cholinergic striatal interneurons may eventually be of therapeutic value for the treatment of Parkinson's disease. ..
  17. Santa N, Kitazono T, Ago T, Ooboshi H, Kamouchi M, Wakisaka M, et al. ATP-sensitive potassium channels mediate dilatation of basilar artery in response to intracellular acidification in vivo. Stroke. 2003;34:1276-80 pubmed
    ..The objective of the present study was to examine the mechanisms by which intracellular acidosis produces dilatation of the basilar artery in vivo...
  18. Du Q, Jovanović S, Sukhodub A, Jovanović A. Infection with AV-SUR2A protects H9C2 cells against metabolic stress: a mechanism of SUR2A-mediated cytoprotection independent from the K(ATP) channel activity. Biochim Biophys Acta. 2010;1803:405-15 pubmed publisher
    ..2AFA. We conclude that AV-SUR2A increases resistance to metabolic stress in H9C2 cells by increasing the number of sarcolemmal K(ATP) channels and subsarcolemmal ATP. ..
  19. Inagaki N, Tsuura Y, Namba N, Masuda K, Gonoi T, Horie M, et al. Cloning and functional characterization of a novel ATP-sensitive potassium channel ubiquitously expressed in rat tissues, including pancreatic islets, pituitary, skeletal muscle, and heart. J Biol Chem. 1995;270:5691-4 pubmed
  20. Xue H, Zhang Y, Liu G, Wang H. A new ATP-sensitive potassium channel opener protects the kidney from hypertensive damage in spontaneously hypertensive rats. J Pharmacol Exp Ther. 2005;315:501-9 pubmed
  21. Liu C, Liu Y, Shen Z, Miao L, Zhang K, Wang F, et al. Sevoflurane Preconditioning Reduces Intestinal Ischemia-Reperfusion Injury: Role of Protein Kinase C and Mitochondrial ATP-Sensitive Potassium Channel. PLoS ONE. 2015;10:e0141426 pubmed publisher
    ..Our results suggest that pretreatment with 0.5 MAC sevoflurane is as effective as IPC against intestinal IRI. The activation of PKC and mKATP may be involved in the protective mechanisms of SPC. ..
  22. Wang W, Li J, Meng X, Chen Y. Effect of electronic stimulation at Neiguan (PC 6) acupoint on gene expression of adenosine triphosphate-sensitive potassium channel and protein kinases in rats with myocardial ischemia. J Tradit Chin Med. 2015;35:577-82 pubmed
    ..05). Our findings suggest that electronic needling of Neiguan (PC 6) can both reduce the gene expression of KATP and protein kinases in rats with ISO-induced MI. ..
  23. Yamauchi K, Stone A, Stocker S, Kaufman M. Blockade of ATP-sensitive potassium channels prevents the attenuation of the exercise pressor reflex by tempol in rats with ligated femoral arteries. Am J Physiol Heart Circ Physiol. 2012;303:H332-40 pubmed publisher
    ..We conclude that tempol attenuated both reflexes by opening K(ATP) channels, an effect that hyperpolarized muscle afferents stimulated by static contraction or tendon stretch. ..
  24. Facundo H, de Paula J, Kowaltowski A. Mitochondrial ATP-sensitive K+ channels prevent oxidative stress, permeability transition and cell death. J Bioenerg Biomembr. 2005;37:75-82 pubmed
  25. Sampson L, Hayabuchi Y, Standen N, Dart C. Caveolae localize protein kinase A signaling to arterial ATP-sensitive potassium channels. Circ Res. 2004;95:1012-8 pubmed
  26. Wu S, Wu A, Sung R. Identification of two types of ATP-sensitive K+ channels in rat ventricular myocytes. Life Sci. 2007;80:378-87 pubmed
    ..The present results suggest that these two types of K(ATP) channels may functionally be related to the activity of heart cells. ..
  27. Cooper P, McClenaghan C, Chen X, Stary Weinzinger A, Nichols C. Conserved functional consequences of disease-associated mutations in the slide helix of Kir6.1 and Kir6.2 subunits of the ATP-sensitive potassium channel. J Biol Chem. 2017;292:17387-17398 pubmed publisher
    ..1 (KCNJ8) subunit...
  28. Shi Y, Cui N, Shi W, Jiang C. A short motif in Kir6.1 consisting of four phosphorylation repeats underlies the vascular KATP channel inhibition by protein kinase C. J Biol Chem. 2008;283:2488-94 pubmed
    ..1, but not in its close relative Kir6.2, suggests that the vascular K(ATP) channel may have undergone evolutionary optimization, allowing it to be regulated by a variety of vasoconstricting hormones and neurotransmitters...
  29. Morrissey A, Rosner E, Lanning J, Parachuru L, Dhar Chowdhury P, Han S, et al. Immunolocalization of KATP channel subunits in mouse and rat cardiac myocytes and the coronary vasculature. BMC Physiol. 2005;5:1 pubmed
    ..2 and SUR2A subunits, but the distribution of these (and other KATP channel subunits) is poorly defined. We examined the localization of each of the KATP channel subunits in the mouse and rat heart...
  30. Thomzig A, Laube G, Prüss H, Veh R. Pore-forming subunits of K-ATP channels, Kir6.1 and Kir6.2, display prominent differences in regional and cellular distribution in the rat brain. J Comp Neurol. 2005;484:313-30 pubmed
    ..Only in distinct nuclei or neuronal subpopulations is a moderate or even strong Kir6.1 staining detected. The biological functions of these K-ATP channels still need to be elucidated...
  31. Cao C, Lee Kwon W, Silldorff E, Pallone T. KATP channel conductance of descending vasa recta pericytes. Am J Physiol Renal Physiol. 2005;289:F1235-45 pubmed
    ..We conclude that DVR pericytes express K(ATP) channels that make a significant contribution to basal K(+) conductance and are inhibited by ANG II and endothelin-1...
  32. Isidoro Tavares N, Philip Couderc P, Papageorgiou I, Baertschi A, Lerch R, Montessuit C. Expression and function of ATP-dependent potassium channels in late post-infarction remodeling. J Mol Cell Cardiol. 2007;42:1016-25 pubmed
    ..Drugs selectively activating diazoxide-sensitive sarcolemmal K(ATP) channels should be considered in the prevention of arrhythmias in post-infarction heart failure. ..
  33. Fan L, Tian H, Wang J, Huo J, Hu Z, Ma A, et al. Downregulation of Kir6.1/SUR2B channels in the obese rat aorta. Nutrition. 2009;25:359-63 pubmed publisher
    ..This study was designed to evaluate the contribution of adenosine triphosphate-dependent potassium channels to the increase in blood pressure observed in obese rats...
  34. Szamosfalvi B, Cortes P, Alviani R, Asano K, Riser B, Zasuwa G, et al. Putative subunits of the rat mesangial KATP: a type 2B sulfonylurea receptor and an inwardly rectifying K+ channel. Kidney Int. 2002;61:1739-49 pubmed
    ..From these data, we inferred that MC expressed the components of a mesangial KATP and sought to establish their presence in primary MC...
  35. Cao K, Tang G, Hu D, Wang R. Molecular basis of ATP-sensitive K+ channels in rat vascular smooth muscles. Biochem Biophys Res Commun. 2002;296:463-9 pubmed
    ..Our results for the first time reported the expression of four K(ATP) subunits in same vascular tissues, unmasking the diversity of native K(ATP) channels in vascular SMCs. ..
  36. Zhou M, Tanaka O, Sekiguchi M, He H, Yasuoka Y, Itoh H, et al. ATP-sensitive K+-channel subunits on the mitochondria and endoplasmic reticulum of rat cardiomyocytes. J Histochem Cytochem. 2005;53:1491-500 pubmed
    ..The data obtained in this study will be useful for analyzing the composition of K(ATP) channels of cardiomyocytes and help to understanding the cardioprotective role of K(ATP) channels during heart ischemia...
  37. Ahmad Waza A, Andrabi K, Ul Hussain M. Adenosine-triphosphate-sensitive K+ channel (Kir6.1): a novel phosphospecific interaction partner of connexin 43 (Cx43). Exp Cell Res. 2012;318:2559-66 pubmed publisher
    ..Our data provide an interesting lead about a possible partnership between Cx43 and Kir6.1, which will help in better understanding their role in ischemia/hypoxia preconditioning. ..
  38. Cuong D, Kim N, Joo H, Youm J, Chung J, Lee Y, et al. Subunit composition of ATP-sensitive potassium channels in mitochondria of rat hearts. Mitochondrion. 2005;5:121-33 pubmed
    ..By contrast, SUR1 was not present in mitochondria. These results suggest that mitoKATP channels in rat hearts might comprise a combination of Kir6.1, Kir6.2, and SUR2 subunits...
  39. Blanco Rivero J, Gamallo C, Aras Lopez R, Cobeño L, Cogolludo A, Perez Vizcaino F, et al. Decreased expression of aortic KIR6.1 and SUR2B in hypertension does not correlate with changes in the functional role of K(ATP) channels. Eur J Pharmacol. 2008;587:204-8 pubmed publisher
    ..Our data demonstrate for the first time direct evidence of decreased aortic Kir6.1/SUR2B subunit expression in hypertension, but preserved functional responses to K(ATP) channel openers...
  40. Tsounapi P, Saito M, Dimitriadis F, Kitatani K, Kinoshita Y, Shomori K, et al. The role of K ATP channels on ischemia-reperfusion injury in the rat testis. Life Sci. 2012;90:649-56 pubmed publisher
    ..This is the first study to give evidence for the advantageous effect of cromakalim in the germ cell-specific apoptosis induced by testicular IR. ..
  41. Ploug K, Amrutkar D, Baun M, Ramachandran R, Iversen A, Lund T, et al. K(ATP) channel openers in the trigeminovascular system. Cephalalgia. 2012;32:55-65 pubmed publisher
    ..Furthermore, we examined whether K(ATP) channel openers stimulate the in vitro release of CGRP and whether they degranulate dural mast cells...
  42. Zhou M, He H, Suzuki R, Tanaka O, Sekiguchi M, Yasuoka Y, et al. Expression of ATP sensitive K+ channel subunit Kir6.1 in rat kidney. Eur J Histochem. 2007;51:43-51 pubmed
    ..1 is mainly localized in the mitochondria, endoplasmic reticulum (ER), and very weakly in cell membranes. Thus, Kir6.1 is contained in the kidney and may be a candidate of mitochondrial K(ATP) channels. ..
  43. Aggarwal N, Shi N, Makielski J. ATP-sensitive potassium currents from channels formed by Kir6 and a modified cardiac mitochondrial SUR2 variant. Channels (Austin). 2013;7:493-502 pubmed publisher
    ..These results suggest that the SUR2A-55 based channels would tend to be open under physiological conditions and in ischemia, and could account for cardiac and mitochondrial phenotypes protective for ischemia. ..
  44. Wang S, Hu L, Yang Y, Ding J, Hu G. Studies of ATP-sensitive potassium channels on 6-hydroxydopamine and haloperidol rat models of Parkinson's disease: implications for treating Parkinson's disease?. Neuropharmacology. 2005;48:984-92 pubmed
    ..Our results suggest that KATP channels might be involved in the pathogenesis of Parkinson's disease (PD) induced in an animal model and conceptually support the idea that KATP channels may be new therapeutic targets for PD. ..
  45. Yang Y, Shi Y, Guo S, Zhang S, Cui N, Shi W, et al. PKA-dependent activation of the vascular smooth muscle isoform of KATP channels by vasoactive intestinal polypeptide and its effect on relaxation of the mesenteric resistance artery. Biochim Biophys Acta. 2008;1778:88-96 pubmed
    ..These results therefore indicate that the vascular isoform (Kir6.1/SUR2B) of KATP channels is a target of VIP. The channel activation relies on the PKA pathway and produces mesenteric arterial relaxation...
  46. Philip Couderc P, Tavares N, Roatti A, Lerch R, Montessuit C, Baertschi A. Forkhead transcription factors coordinate expression of myocardial KATP channel subunits and energy metabolism. Circ Res. 2008;102:e20-35 pubmed publisher
    ..Thus, FoxF2 and -O are key transcription factors coordinating expression of KATP channels and energy metabolism. ..
  47. Leroy C, Privé A, Bourret J, Berthiaume Y, Ferraro P, Brochiero E. Regulation of ENaC and CFTR expression with K+ channel modulators and effect on fluid absorption across alveolar epithelial cells. Am J Physiol Lung Cell Mol Physiol. 2006;291:L1207-19 pubmed
    ..Long-term regulation of ENaC and CFTR expression by K(+) channel activity could benefit patients with pulmonary diseases affecting ion transport and fluid clearance. ..
  48. Ljubkovic M, Shi Y, Cheng Q, Bosnjak Z, Jiang M. Cardiac mitochondrial ATP-sensitive potassium channel is activated by nitric oxide in vitro. FEBS Lett. 2007;581:4255-9 pubmed
    ..This activation was inhibited by mitoK(ATP) blockers 5-hydroxydecanoate or glibenclamide. Our observations confirm that NO can directly activate the cardiac mitoK(ATP), which may underlie its contribution to myocardial preconditioning...
  49. Davies L, Purves G, Barrett Jolley R, Dart C. Interaction with caveolin-1 modulates vascular ATP-sensitive potassium (KATP) channel activity. J Physiol. 2010;588:3255-66 pubmed publisher
  50. Croker B, Crozat K, Berger M, Xia Y, Sovath S, Schaffer L, et al. ATP-sensitive potassium channels mediate survival during infection in mammals and insects. Nat Genet. 2007;39:1453-60 pubmed
    ..The phenotype is due to a null allele of Kcnj8, encoding Kir6...