kcnq1 potassium channel


Summary: A voltage-gated potassium channel that is expressed primarily in the HEART.

Top Publications

  1. Tsai F, Yang C, Chen C, Chuang L, Lu C, Chang C, et al. A genome-wide association study identifies susceptibility variants for type 2 diabetes in Han Chinese. PLoS Genet. 2010;6:e1000847 pubmed publisher
  2. Smith J, Vanoye C, George A, Meiler J, Sanders C. Structural models for the KCNQ1 voltage-gated potassium channel. Biochemistry. 2007;46:14141-52 pubmed
    ..This interface evidently plays an important role in channel gating. ..
  3. Nishio H, Kuwahara M, Tsubone H, Koda Y, Sato T, Fukunishi S, et al. Identification of an ethnic-specific variant (V207M) of the KCNQ1 cardiac potassium channel gene in sudden unexplained death and implications from a knock-in mouse model. Int J Legal Med. 2009;123:253-7 pubmed publisher
    ..Significant prolongation of QT intervals was observed in the Kcnq1(V206M/V206M) mice. These findings suggest that the KCNQ1-V207M mutation might be pathogenic and might have been associated with the cause of death in the present case. ..
  4. Das S, Makino S, Melman Y, Shea M, Goyal S, Rosenzweig A, et al. Mutation in the S3 segment of KCNQ1 results in familial lone atrial fibrillation. Heart Rhythm. 2009;6:1146-53 pubmed publisher
    ..We identified a family with lone AF due to a mutation in the highly conserved S3 domain of KCNQ1, a region of the channel not previously implicated in the pathogenesis of AF. ..
  5. Morokuma J, Blackiston D, Levin M. KCNQ1 and KCNE1 K+ channel components are involved in early left-right patterning in Xenopus laevis embryos. Cell Physiol Biochem. 2008;21:357-72 pubmed publisher
    ..Our data reveal a new, bioelectrical component of the mechanisms patterning a large-scale axis in vertebrate embryogenesis. ..
  6. Nicolas C, Park K, El Harchi A, Camonis J, Kass R, Escande D, et al. IKs response to protein kinase A-dependent KCNQ1 phosphorylation requires direct interaction with microtubules. Cardiovasc Res. 2008;79:427-35 pubmed publisher
    ..We propose that the KCNQ1-KCNE1 channel directly interacts with microtubules and that this interaction plays a major role in coupling PKA-dependent phosphorylation of KCNQ1 with I(Ks) activation. ..
  7. Holmkvist J, Banasik K, Andersen G, Unoki H, Jensen T, Pisinger C, et al. The type 2 diabetes associated minor allele of rs2237895 KCNQ1 associates with reduced insulin release following an oral glucose load. PLoS ONE. 2009;4:e5872 pubmed publisher
  8. Lee Y, Kang E, Kim S, Han S, Kim C, Kim H, et al. Association between polymorphisms in SLC30A8, HHEX, CDKN2A/B, IGF2BP2, FTO, WFS1, CDKAL1, KCNQ1 and type 2 diabetes in the Korean population. J Hum Genet. 2008;53:991-8 pubmed publisher
    ..In conclusion, we have shown that SNPs in HHEX, CDKN2A/B, CDKAL1, KCNQ1 and SLC30A8 confer a risk of T2DM in the Korean population. ..
  9. Mruk K, Kobertz W. Discovery of a novel activator of KCNQ1-KCNE1 K channel complexes. PLoS ONE. 2009;4:e4236 pubmed publisher
    ..Furthermore, the commercial availability of numerous PBA derivatives provides a large class of compounds to investigate the gating mechanisms of KCNQ1-KCNE complexes. ..

More Information


  1. Wang Y, Jiang M, Xu X, Hsu K, Zhang M, Tseng G. Gating-related molecular motions in the extracellular domain of the IKs channel: implications for IKs channelopathy. J Membr Biol. 2011;239:137-56 pubmed publisher
    ..These data and the proposed molecular motions provide insights into the mechanisms by which mutations in the extracellular juxtamembranous region of the I(Ks) channel impair its function. ..
  2. Takeuchi F, Serizawa M, Yamamoto K, Fujisawa T, Nakashima E, Ohnaka K, et al. Confirmation of multiple risk Loci and genetic impacts by a genome-wide association study of type 2 diabetes in the Japanese population. Diabetes. 2009;58:1690-9 pubmed publisher
    ..The strength of association was more prominent in the Japanese population than in Europeans for more than half of the confirmed type 2 diabetes loci. ..
  3. Zhang Y, Chang B, Hu S, Wang D, Fang Q, Huang X, et al. Single nucleotide polymorphisms and haplotype of four genes encoding cardiac ion channels in Chinese and their association with arrhythmia. Ann Noninvasive Electrocardiol. 2008;13:180-90 pubmed publisher
    ..Our study provided important information to elucidate the effect of SNPs of cardiac ion channel genes on channel function and susceptibility to cardiac arrhythmias in Chinese population. ..
  4. Albert C, Macrae C, Chasman D, VanDenburgh M, Buring J, Manson J, et al. Common variants in cardiac ion channel genes are associated with sudden cardiac death. Circ Arrhythm Electrophysiol. 2010;3:222-9 pubmed publisher
    ..Further study in other populations and investigation into the functional abnormalities associated with noncoding variation in these genes may lead to important insights into predisposition to lethal arrhythmias. ..
  5. Sun Q, Song K, Shen X, Cai Y. The association between KCNQ1 gene polymorphism and type 2 diabetes risk: a meta-analysis. PLoS ONE. 2012;7:e48578 pubmed publisher
    ..This meta-analysis suggests that the rs2237892 and rs2237895 polymorphisms in KCNQ1 are associated with elevated type 2 diabetes susceptibility. ..
  6. Meisel E, Dvir M, Haitin Y, Giladi M, Peretz A, Attali B. KCNQ1 channels do not undergo concerted but sequential gating transitions in both the absence and the presence of KCNE1 protein. J Biol Chem. 2012;287:34212-24 pubmed publisher
    ..Our data suggest that KCNQ1 channels in both the absence and the presence of KCNE1 undergo sequential gating transitions leading to channel opening even before all VSDs have moved. ..
  7. Zhou J, Yang J, Zhao L, Xin Z. Variants in KCNQ1, AP3S1, MAN2A1, and ALDH7A1 and the risk of type 2 diabetes in the Chinese Northern Han population: a case-control study and meta-analysis. Med Sci Monit. 2010;16:BR179-83 pubmed
    ..05). Meta-analysis yielded an OR of 1.36 (95%CI: 1.23-1.51) for rs2237892. In this study the effects of KCNQ1 and AP3S1 variants on susceptibility to T2D in the Chinese Northern Han population were confirmed. ..
  8. Yeung S, Schwake M, Pucovsky V, Greenwood I. Bimodal effects of the Kv7 channel activator retigabine on vascular K+ currents. Br J Pharmacol. 2008;155:62-72 pubmed publisher
    ..This study investigated the functional and electrophysiological effects of the Kv7 channel activator, retigabine, on murine portal vein smooth muscle...
  9. Tan J, Nurbaya S, Gardner D, Ye S, Tai E, Ng D. Genetic variation in KCNQ1 associates with fasting glucose and beta-cell function: a study of 3,734 subjects comprising three ethnicities living in Singapore. Diabetes. 2009;58:1445-9 pubmed publisher
    ..Further studies will be useful to replicate these findings and to fully delineate the role of KCNQ1 and its related pathways in disease pathogenesis. ..
  10. Lundby A, Tseng G, Schmitt N. Structural basis for K(V)7.1-KCNE(x) interactions in the I(Ks) channel complex. Heart Rhythm. 2010;7:708-13 pubmed publisher
    ..Here we review recent studies in this area and discuss potential roles for multiple KCNE(x) subunits in I(Ks) generation and modulation as well as the clinical relevance of the new information. ..
  11. Lundby A, Ravn L, Svendsen J, Olesen S, Schmitt N. KCNQ1 mutation Q147R is associated with atrial fibrillation and prolonged QT interval. Heart Rhythm. 2007;4:1532-41 pubmed
    ..The mechanism may be heterogeneous distribution of Kv7.1 accessory subunits in the heart leading to Kv7.1 gain of function in the atria (for AF) and Kv7.1 loss of function in the ventricles (for QT prolongation). ..
  12. Liu X, Zhang M, Jiang M, Wu D, Tseng G. Probing the interaction between KCNE2 and KCNQ1 in their transmembrane regions. J Membr Biol. 2007;216:117-27 pubmed
    ..We propose that the KCNE2 TMD adopts an alpha-helical secondary structure with one face making intimate contact with the KCNQ1 pore domain, while the contacts with the KCNQ1 voltage-sensing domain appear more dynamic. ..
  13. Osteen J, Gonzalez C, Sampson K, Iyer V, Rebolledo S, Larsson H, et al. KCNE1 alters the voltage sensor movements necessary to open the KCNQ1 channel gate. Proc Natl Acad Sci U S A. 2010;107:22710-5 pubmed publisher
    ..This work provides insight into the mechanism by which KCNE1 modulates the I(Ks) channel and presents a mechanism for distinct ?-subunit regulation of ion channel proteins. ..
  14. Eddy C, MacCormick J, Chung S, Crawford J, Love D, Rees M, et al. Identification of large gene deletions and duplications in KCNQ1 and KCNH2 in patients with long QT syndrome. Heart Rhythm. 2008;5:1275-81 pubmed publisher
    ..As such, these findings suggest that sequencing-based mutation detection strategies should be followed by deletion/duplication screening in all LQTS mutation-negative patients. ..
  15. Silva J, Pan H, Wu D, Nekouzadeh A, Decker K, Cui J, et al. A multiscale model linking ion-channel molecular dynamics and electrostatics to the cardiac action potential. Proc Natl Acad Sci U S A. 2009;106:11102-6 pubmed publisher
    ..This framework allows integration of multiscale observations to study the molecular basis of excitation and its alteration by disease. ..
  16. Manderfield L, Daniels M, Vanoye C, George A. KCNE4 domains required for inhibition of KCNQ1. J Physiol. 2009;587:303-14 pubmed publisher
    ..We further demonstrated that the KCNE4 C-terminus interacts with KCNQ1. Our data reveal important structure-function relationships for KCNE4 that help advance our understanding of potassium channel modulation by KCNE proteins. ..
  17. Wang H, Iguchi N, Rong Q, Zhou M, Ogunkorode M, Inoue M, et al. Expression of the voltage-gated potassium channel KCNQ1 in mammalian taste bud cells and the effect of its null-mutation on taste preferences. J Comp Neurol. 2009;512:384-98 pubmed publisher
  18. Unoki H, Takahashi A, Kawaguchi T, Hara K, Horikoshi M, Andersen G, et al. SNPs in KCNQ1 are associated with susceptibility to type 2 diabetes in East Asian and European populations. Nat Genet. 2008;40:1098-102 pubmed publisher
    ..5 x 10(-3); OR = 1.14, rs2237897, P = 2.4 x 10(-4); OR = 1.22) and Danish populations (additive model: rs2237895, P = 3.7 x 10(-11); OR = 1.24, rs2237897, P = 1.2 x 10(-4); OR = 1.36). ..
  19. Barsheshet A, Goldenberg I, O Uchi J, Moss A, Jons C, Shimizu W, et al. Mutations in cytoplasmic loops of the KCNQ1 channel and the risk of life-threatening events: implications for mutation-specific response to ?-blocker therapy in type 1 long-QT syndrome. Circulation. 2012;125:1988-96 pubmed publisher
    ..Reduced channel activation after sympathetic activation can explain the increased clinical risk and response to therapy in patients with C-loop mutations. ..
  20. van Vliet Ostaptchouk J, van Haeften T, Landman G, Reiling E, Kleefstra N, Bilo H, et al. Common variants in the type 2 diabetes KCNQ1 gene are associated with impairments in insulin secretion during hyperglycaemic glucose clamp. PLoS ONE. 2012;7:e32148 pubmed publisher
    ..Furthermore, our data suggest that KCNQ1 is also associated with lipid metabolism. ..
  21. Shamgar L, Haitin Y, Yisharel I, Malka E, Schottelndreier H, Peretz A, et al. KCNE1 constrains the voltage sensor of Kv7.1 K+ channels. PLoS ONE. 2008;3:e1943 pubmed publisher
    ..1 gating functions. ..
  22. Cemerikic D, Nesovic Ostojic J, Popadic D, Knezevic A, Dragovic S, Milovanovic A, et al. Absence of KCNQ1-dependent K+ fluxes in proximal tubular cells of frog kidney. Comp Biochem Physiol A Mol Integr Physiol. 2007;148:635-44 pubmed
    ..RT-PCR showed that KCNQ1 mRNA was not expressed in frog kidney. In conclusion, the KCNQ1-dependent K+ secretory fluxes are absent in proximal tubule of frog kidney...
  23. Seebohm G, Strutz Seebohm N, Ureche O, Henrion U, Baltaev R, Mack A, et al. Long QT syndrome-associated mutations in KCNQ1 and KCNE1 subunits disrupt normal endosomal recycling of IKs channels. Circ Res. 2008;103:1451-7 pubmed publisher
    ..Identification of the I(Ks) recycling pathway and its modulation by stress-stimulated SGK1 provides novel mechanistic insight into potentially fatal cardiac arrhythmias triggered by physical or psychological stress. ..
  24. Miceli F, Soldovieri M, Martire M, Taglialatela M. Molecular pharmacology and therapeutic potential of neuronal Kv7-modulating drugs. Curr Opin Pharmacol. 2008;8:65-74 pubmed
  25. Chan P, Osteen J, Xiong D, Bohnen M, Doshi D, Sampson K, et al. Characterization of KCNQ1 atrial fibrillation mutations reveals distinct dependence on KCNE1. J Gen Physiol. 2012;139:135-44 pubmed publisher
  26. Ma L, Ohmert I, Vardanyan V. Allosteric features of KCNQ1 gating revealed by alanine scanning mutagenesis. Biophys J. 2011;100:885-94 pubmed publisher
    ..Allosteric features are discussed in the context of extreme gating adaptability of KCNQ1 upon interaction with KCNE ?-subunits. ..
  27. Moretti A, Bellin M, Welling A, Jung C, Lam J, Bott Flügel L, et al. Patient-specific induced pluripotent stem-cell models for long-QT syndrome. N Engl J Med. 2010;363:1397-409 pubmed publisher
    ..In long-QT syndrome type 1, mutations occur in the KCNQ1 gene, which encodes the repolarizing potassium channel mediating the delayed rectifier I(Ks) current...
  28. Chen Z, Yin Q, Ma G, Qian Q. KCNQ1 gene polymorphisms are associated with lipid parameters in a Chinese Han population. Cardiovasc Diabetol. 2010;9:35 pubmed publisher
    ..No other associations were detected between these 4 SNPs and FBS or other lipid parameters. Our data suggest that rs2283228 and rs2237892 in KCNQ1 are associated with lipid metabolism in a middle-aged Chinese Han population. ..
  29. Restier L, Cheng L, Sanguinetti M. Mechanisms by which atrial fibrillation-associated mutations in the S1 domain of KCNQ1 slow deactivation of IKs channels. J Physiol. 2008;586:4179-91 pubmed publisher
    ..Together our findings suggest that altered charge-pair interactions within the voltage sensor module of KCNQ1 subunits may account for slowed I(Ks) deactivation induced by S140 or V141. ..
  30. Lvov A, Gage S, Berrios V, Kobertz W. Identification of a protein-protein interaction between KCNE1 and the activation gate machinery of KCNQ1. J Gen Physiol. 2010;135:607-18 pubmed publisher
    ..Based on these biochemical and electrophysiological data, we generated a closed-state model of the KCNQ1-KCNE1 cytoplasmic region where these protein-protein interactions are poised to slow activation gate opening. ..
  31. Egashira T, Yuasa S, Suzuki T, Aizawa Y, Yamakawa H, Matsuhashi T, et al. Disease characterization using LQTS-specific induced pluripotent stem cells. Cardiovasc Res. 2012;95:419-29 pubmed publisher
    ..This study demonstrated that iPSCs could be useful to characterize LQTS disease as well as drug responses in the LQTS patient with a novel mutation. Such analyses may in turn lead to future progress in personalized medicine. ..
  32. Werry D, Eldstrom J, Wang Z, Fedida D. Single-channel basis for the slow activation of the repolarizing cardiac potassium current, I(Ks). Proc Natl Acad Sci U S A. 2013;110:E996-1005 pubmed publisher
    ..Fast closings and overt subconductance behavior of the wild-type I(Ks) channel required modification of existing Markov models to include these features of channel behavior. ..
  33. Nakajo K, Ulbrich M, Kubo Y, Isacoff E. Stoichiometry of the KCNQ1 - KCNE1 ion channel complex. Proc Natl Acad Sci U S A. 2010;107:18862-7 pubmed publisher
  34. Wiener R, Haitin Y, Shamgar L, Fernández Alonso M, Martos A, Chomsky Hecht O, et al. The KCNQ1 (Kv7.1) COOH terminus, a multitiered scaffold for subunit assembly and protein interaction. J Biol Chem. 2008;283:5815-30 pubmed publisher
    ..Functional studies, including characterization of structure-based and long QT mutants, prove the requirement for both modules and point to complex roles for these modules, including folding, assembly, trafficking, and regulation. ..
  35. Morin T, Kobertz W. Counting membrane-embedded KCNE beta-subunits in functioning K+ channel complexes. Proc Natl Acad Sci U S A. 2008;105:1478-82 pubmed publisher
    ..Moreover, the architectural asymmetry of the K(+) channel complex affords a unique opportunity to therapeutically target ion channels that coassemble with KCNE beta-subunits. ..
  36. Haitin Y, Yisharel I, Malka E, Shamgar L, Schottelndreier H, Peretz A, et al. S1 constrains S4 in the voltage sensor domain of Kv7.1 K+ channels. PLoS ONE. 2008;3:e1935 pubmed publisher
    ..These constraints provide a ground for cooperative subunit interactions and suggest a key role of the S1 segment in steering S4 motion during Kv7.1 gating. ..
  37. Xu X, Jiang M, Hsu K, Zhang M, Tseng G. KCNQ1 and KCNE1 in the IKs channel complex make state-dependent contacts in their extracellular domains. J Gen Physiol. 2008;131:589-603 pubmed publisher
    ..We propose that E1 is not a passive partner of the Q1 channel, but instead can engage in molecular motions during I(Ks) gating. ..
  38. Etheridge S, Sanatani S, Cohen M, Albaro C, Saarel E, Bradley D. Long QT syndrome in children in the era of implantable defibrillators. J Am Coll Cardiol. 2007;50:1335-40 pubmed
    ..In the era of genetic testing and device implantation, overall mortality is low with treatment. Device therapy, although effective, is not without complications and should be reserved for high-risk patients. ..
  39. Abraham R, Yang T, Blair M, Roden D, Darbar D. Augmented potassium current is a shared phenotype for two genetic defects associated with familial atrial fibrillation. J Mol Cell Cardiol. 2010;48:181-90 pubmed publisher
  40. Manderfield L, George A. KCNE4 can co-associate with the I(Ks) (KCNQ1-KCNE1) channel complex. FEBS J. 2008;275:1336-49 pubmed publisher
    ..The observation that multiple KCNE proteins can co-associate with and modulate KCNQ1 channels to produce biochemically diverse channel complexes has important implications for understanding K(V) channel regulation in human physiology. ..
  41. Li Y, Zaydman M, Wu D, Shi J, Guan M, Virgin Downey B, et al. KCNE1 enhances phosphatidylinositol 4,5-bisphosphate (PIP2) sensitivity of IKs to modulate channel activity. Proc Natl Acad Sci U S A. 2011;108:9095-100 pubmed publisher
    ..These results reveal a vital role of PIP(2) for KCNE1 modulation of I(Ks) channels that may represent a common mechanism of auxiliary subunit modulation of many ion channels...
  42. Peroz D, Dahimene S, Baró I, Loussouarn G, Merot J. LQT1-associated mutations increase KCNQ1 proteasomal degradation independently of Derlin-1. J Biol Chem. 2009;284:5250-6 pubmed publisher
    ..Small interfering RNA knock-down of Derlin-1 did not modify KCNQ1 expression level, and no interaction between endogenous KCNQ1 and Derlin-1 could be detected. ..
  43. Chung D, Chan P, Bankston J, Yang L, Liu G, Marx S, et al. Location of KCNE1 relative to KCNQ1 in the I(KS) potassium channel by disulfide cross-linking of substituted cysteines. Proc Natl Acad Sci U S A. 2009;106:743-8 pubmed publisher
    ..Thus, the first E1 orientation strongly favors the open state, while the approximately opposite orientation favors the closed state. ..
  44. Choveau F, Rodriguez N, Abderemane Ali F, Labro A, Rose T, Dahimene S, et al. KCNQ1 channels voltage dependence through a voltage-dependent binding of the S4-S5 linker to the pore domain. J Biol Chem. 2011;286:707-16 pubmed publisher
    ..This interaction locks the channel in a closed state. Upon plasma membrane depolarization, S4 pulls S4S5(L) away from S6(T), allowing channel opening. ..
  45. Pfeufer A, Sanna S, Arking D, Müller M, Gateva V, Fuchsberger C, et al. Common variants at ten loci modulate the QT interval duration in the QTSCD Study. Nat Genet. 2009;41:407-14 pubmed publisher
    ..These results, together with an accompanying paper from the QTGEN consortium, identify new candidate genes for ventricular arrhythmias and SCD. ..
  46. Hu C, Wang C, Zhang R, Ma X, Wang J, Lu J, et al. Variations in KCNQ1 are associated with type 2 diabetes and beta cell function in a Chinese population. Diabetologia. 2009;52:1322-5 pubmed publisher
    ..0334 and p = 0.0002, respectively). In this study we found that KCNQ1 was associated with type 2 diabetes susceptibility in a Chinese population, possibly through its effect on beta cell function. ..
  47. Chen J, Zheng R, Melman Y, McDonald T. Functional interactions between KCNE1 C-terminus and the KCNQ1 channel. PLoS ONE. 2009;4:e5143 pubmed publisher
    ..These results support several roles for KCNE1 C-terminus interaction with KCNQ1: regulation of channel assembly, open-state destabilization, and kinetics of channel deactivation. ..
  48. Yasuda K, Miyake K, Horikawa Y, Hara K, Osawa H, Furuta H, et al. Variants in KCNQ1 are associated with susceptibility to type 2 diabetes mellitus. Nat Genet. 2008;40:1092-7 pubmed publisher
    ..Our data thus implicate KCNQ1 as a diabetes susceptibility gene in groups of different ancestries. ..
  49. Saif Ali R, Muniandy S, Al Hamodi Z, Lee C, Ahmed K, Al Mekhlafi A, et al. KCNQ1 variants associate with type 2 diabetes in Malaysian Malay subjects. Ann Acad Med Singapore. 2011;40:488-92 pubmed
    ..003). Furthermore, the diplotype (CAA-TCA) that contained the protective haplotype was protected against T2D (OR = 0.46, P = 0.006). The KCNQ1 SNPs, haplotypes and diplotypes are associated with T2D in the Malaysian Malay subjects. ..
  50. Gao Z, Xiong Q, Sun H, Li M. Desensitization of chemical activation by auxiliary subunits: convergence of molecular determinants critical for augmenting KCNQ1 potassium channels. J Biol Chem. 2008;283:22649-58 pubmed publisher
    ..Thus, the convergence of potentiation effects and molecular determinants critical for both an auxiliary subunit and a chemical opener argue for a mechanistic overlap in causing potentiation. ..
  51. Schwartz P, Vanoli E, Crotti L, Spazzolini C, Ferrandi C, Goosen A, et al. Neural control of heart rate is an arrhythmia risk modifier in long QT syndrome. J Am Coll Cardiol. 2008;51:920-9 pubmed publisher
    ..These findings help understanding phenotypic heterogeneity in LQTS and identify a physiological risk modifier, which is probably genetically determined. ..
  52. Müssig K, Staiger H, Machicao F, Kirchhoff K, Guthoff M, Schäfer S, et al. Association of type 2 diabetes candidate polymorphisms in KCNQ1 with incretin and insulin secretion. Diabetes. 2009;58:1715-20 pubmed publisher
    ..The discrepancy between orally and intravenously administered glucose seems to be explained not by altered incretin signaling but most likely by changes in incretin secretion. ..
  53. Chen Z, Zhang X, Ma G, Qian Q, Yao Y. Association study of four variants in KCNQ1 with type 2 diabetes mellitus and premature coronary artery disease in a Chinese population. Mol Biol Rep. 2010;37:207-12 pubmed publisher
    ..05). Our data implicate rs2237892 in KCNQ1 as a protective gene variant against premature CAD and we couldn't replicate any association of these 4 SNPs with T2DM or extent of coronary lesions in a Chinese population. ..