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The voltage-gated channel accessory protein KCNE2: multiple ion channel partners, multiple ways to long QT syndrome

  • Jodene Eldstrom (a1) and David Fedida (a1)

The single-pass transmembrane protein KCNE2 or MIRP1 was once thought to be the missing accessory protein that combined with hERG to fully recapitulate the cardiac repolarising current IKr. As a result of this role, it was an easy next step to associate mutations in KCNE2 to long QT syndrome, in which there is delayed repolarisation of the heart. Since that time however, KCNE2 has been shown to modify the behaviour of several other channels and currents, and its role in the heart and in the aetiology of long QT syndrome has become less clear. In this article, we review the known interactions of the KCNE2 protein and the resulting functional effects, and the effects of mutations in KCNE2 and their clinical role.

Corresponding author
*Corresponding author: David Fedida, Department of Anesthesiology, Pharmacology and Therapeutics, University of British Columbia, 2176 Health Sciences Mall, Vancouver, BC, CanadaV6T 1Z3. E-mail:
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1S.G. Priori (2003) Risk stratification in the long-QT syndrome. New England Journal of Medicine 348, 1866-1874

2A.A. Wilde (1999) Auditory stimuli as a trigger for arrhythmic events differentiate HERG-related (LQTS2) patients from KVLQT1-related patients (LQTS1). Journal of the American College of Cardiology 33, 327-332

3C. van Noord , M. Eijgelsheim and B.H.C. Stricker (2010) Drug- and non-drug-associated QT interval prolongation. British Journal of Clinical Pharmacology 70, 16-23

4G.W. Abbott (1999) MiRP1 forms IKr potassium channels with HERG and is associated with cardiac arrhythmia. Cell 97, 175-187

5J.N. Johnson and M.J. Ackerman (2009) QTc: how long is too long? British Journal of Sports Medicine 43, 657-662

6P.J. Schwartz (2009) Prevalence of the congenital long-QT syndrome. Circulation 120, 1761-1767

7C. van der Werf (2010) Diagnostic yield in sudden unexplained death and aborted cardiac arrest in the young: the experience of a tertiary referral center in The Netherlands. Heart Rhythm 7, 1383-1389

8P.J. Schwartz (1998) Prolongation of the QT interval and the sudden infant death syndrome. New England Journal of Medicine 338, 1709-1714

9J.D. Kapplinger (2009) Spectrum and prevalence of mutations from the first 2,500 consecutive unrelated patients referred for the FAMILION long QT syndrome genetic test. Heart Rhythm 6, 1297-1303

10P. Westenskow (2004) Compound mutations: a common cause of severe long-QT syndrome. Circulation 109, 1834-1841

11D.J. Tester and M.J. Ackerman (2009) Cardiomyopathic and channelopathic causes of sudden unexplained death in infants and children. Annual Review of Medicine 60, 69-84

12G. Romey (1997) Molecular mechanism and functional significance of the MinK control of the KvLQT1 channel activity. Journal of Biological Chemistry 272, 16713-16716

13M.C. Sanguinetti (1996) Coassembly of KvLQT1 and minK (IsK) proteins to form cardiac IKs potassium channel. Nature 384, 80-83

14J. Barhanin (1996) KvLQT1 and IsK (minK) proteins associate to form the IKs cardiac potassium current. Nature 384, 78-80

15P.J. Mohler (2003) Ankyrin-B mutation causes type 4 long-QT cardiac arrhythmia and sudden cardiac death. Nature 421, 634-639

16A. Medeiros-Domingo (2007) SCN4B-encoded sodium channel beta4 subunit in congenital long-QT syndrome. Circulation 116, 134-142

17P.J. Mohler (2007) Defining the cellular phenotype of ‘ankyrin-B syndrome’ variants: human ANK2 variants associated with clinical phenotypes display a spectrum of activities in cardiomyocytes. Circulation 115, 432-441

18M. Vatta (2006) Mutant caveolin-3 induces persistent late sodium current and is associated with long-QT syndrome. Circulation 114, 2104-2112

() Mutation of an A-kinase-anchoring protein causes long-QT syndrome. , -19L. Chen 2007 Proceedings of the National Academy of Sciences of the United States of America 104 2099020995

20Y.Z. Yang (2010) Identification of a Kir3.4 mutation in congenital long QT syndrome. American Journal of Human Genetics 86, 872-880

21J. Barc (2011) Screening for copy number variation in genes associated with the long QT syndrome: clinical relevance. Journal of the American College of Cardiology 57, 40-47

22J.M. Nerbonne and R.S. Kass (2005) Molecular physiology of cardiac repolarization. Physiological Reviews 85, 1205-1253

23A.S. Amin , H.L. Tan and A.A. Wilde (2010) Cardiac ion channels in health and disease. Heart Rhythm 7, 117-126

24D. DiFrancesco (2010) The role of the funny current in pacemaker activity. Circulation Research 106, 434-446

25D. Fedida (1993) Identity of a novel delayed rectifier current from human heart with a cloned K+ channel current. Circulation Research 73, 210-216

26J.L. Feng (1997) Antisense oligodeoxynucleotides directed against Kv1.5 mRNA specifically inhibit ultrarapid delayed rectifier K+ current in cultured adult human atrial myocytes. Circulation Research 80, 572-579

27M.B. Boyle (1987) Xenopus oocytes injected with rat urine RNA express very slowly activating potassium currents. Science 235, 1221-1224

28T. Takumi , H. Ohkubo and S. Nakanishi (1988) Cloning of a membrane protein that induces a slow voltage-gated potassium current. Science 242, 1042-1045

29M. Piccini (1999) KCNE1-like gene is deleted in AMME contiguous gene syndrome: identification and characterization of the human and mouse homologs. Genomics 60, 251-257

30A.L. Lundquist (2005) Expression of multiple KCNE genes in human heart may enable variable modulation of I(Ks). Journal of Molecular and Cellular Cardiology 38, 277-287

32S. Teng (2003) Novel gene hKCNE4 slows the activation of the KCNQ1 channel. Biochemical and Biophysical Research Communications 303, 808-813

34S.D. Gage and W.R. Kobertz (2004) KCNE3 truncation mutants reveal a bipartite modulation of KCNQ1K+ channels. Journal of General Physiology 124, 759-771

35G.W. Abbott , M.H. Butler and S.A. Goldstein (2006) Phosphorylation and protonation of neighboring MiRP2 sites: function and pathophysiology of MiRP2-Kv3.4 potassium channels in periodic paralysis. FASEB Journal 20, 293-301

36E.J. Ciampa (2011) KCNE4 juxtamembrane region is required for interaction with calmodulin and for functional suppression of KCNQ1. Journal of Biological Chemistry 286, 4141-4149

37S.B. Long , E.B. Campbell and R. MacKinnon (2005) Crystal structure of a mammalian voltage-dependent Shaker family K+ channel. Science 309, 897-903

38S.B. Long (2007) Atomic structure of a voltage-dependent K+ channel in a lipid membrane-like environment. Nature 450, 376-382

39K.D. Chandrasekhar , T. Bas and W.R. Kobertz (2006) KCNE1 subunits require co-assembly with K+ channels for efficient trafficking and cell surface expression. Journal of Biological Chemistry 281, 40015-40023

40C.G. Vanoye (2010) KCNQ1/KCNE1 assembly, co-translation not required. Channels (Austin) 4, 108-114

42C. Kang (2008) Structure of KCNE1 and implications for how it modulates the KCNQ1 potassium channel. Biochemistry 47, 7999-8006

43Y.F. Melman (2004) KCNE1 binds to the KCNQ1 pore to regulate potassium channel activity. Neuron 42, 927-937

44S. Chen (2003) KCNQ1 mutations in patients with a family history of lethal cardiac arrhythmias and sudden death. Clinical Genetics 63, 273-282

45D.Y. Chung (2009) Location of KCNE1 relative to KCNQ1 in the I(KS) potassium channel by disulfide cross-linking of substituted cysteines. Proceedings of the National Academy of Sciences of the United States of America 106, 743-748

46X. Xu (2008) KCNQ1 and KCNE1 in the IKs channel complex make state-dependent contacts in their extracellular domains. Journal of General Physiology 131, 589-603

47L. Shamgar (2008) KCNE1 constrains the voltage sensor of Kv7.1K+ channels. PLoS One 3, e1943-

48K. Nakajo and Y. Kubo (2007) KCNE1 and KCNE3 stabilize and/or slow voltage sensing S4 segment of KCNQ1 channel. Journal of General Physiology 130, 269-281

49Y. Haitin (2009) Intracellular domains interactions and gated motions of I(KS) potassium channel subunits. EMBO Journal 28, 1994-2005

50H. Chen (2003) Charybdotoxin binding in the I(Ks) pore demonstrates two MinK subunits in each channel complex. Neuron 40, 15-23

51T.J. Morin and W.R. Kobertz (2008) Counting membrane-embedded KCNE beta-subunits in functioning K+ channel complexes. Proceedings of the National Academy of Sciences of the United States of America 105, 1478-1482

52K. Nakajo (2010) Stoichiometry of the KC. Proceedings of the National Academy of Sciences of the United States of America 107, 18862-18867

53F. Toyoda (2006) Modulation of functional properties of KCNQ1 channel by association of KCNE1 and KCNE2. Biochemical and Biophysical Research Communications 344, 814-820

54M. Jiang (2009) Dynamic partnership between KCNQ1 and KCNE1 and influence on cardiac IKs current amplitude by KCNE2. Journal of Biological Chemistry 284, 16452-16462

55Z.A. McCrossan (2009) Regulation of the Kv2.1 potassium channel by MinK and MiRP1. Journal of Membrane Biology 228, 1-14

56A. Lewis , Z.A. McCrossan and G.W. Abbott (2004) MinK, MiRP1, and MiRP2 diversify Kv3.1 and Kv3.2 potassium channel gating. Journal of Biological Chemistry 279, 7884-7892

57M. Zhang , M. Jiang and G.N. Tseng (2001) MinK-related peptide 1 associates with Kv4.2 and modulates its gating function – potential role as β subunit of cardiac transient outward channel? Circulation Research 88, 1012-1019

58H. Yu (2001) MinK-related peptide 1: a beta subunit for the HCN ion channel subunit family enhances expression and speeds activation. Circulation Research 88, E84-E87

59N. Decher (2003) KCNE2 modulates current amplitudes and activation kinetics of HCN4: influence of KCNE family members on HCN4 currents. Pflugers Archiv 446, 633-640

60K. Dedek and S. Waldegger (2001) Colocalization of KCNQ1/KCNE channel subunits in the mouse gastrointestinal tract. Pflugers Archiv 442, 896-902

61F. Grahammer (2001) The cardiac K+ channel KCNQ1 is essential for gastric acid secretion. Gastroenterology 120, 1363-1371

62D. Heitzmann (2004) Heteromeric KCNE2/KCNQ1 potassium channels in the luminal membrane of gastric parietal cells. Journal of Physiology 561, 547-557

63N.W. Lambrecht (2005) Identification of the K efflux channel coupled to the gastric H-K-ATPase during acid secretion. Physiological Genomics 21, 81-91

64T.K. Roepke (2006) The KCNE2 potassium channel ancillary subunit is essential for gastric acid secretion. Journal of Biological Chemistry 281, 23740-23747

65D.M. Wu (2006) KCNE2 is colocalized with KCNQ1 and KCNE1 in cardiac myocytes and may function as a negative modulator of I(Ks) current amplitude in the heart. Heart Rhythm 3, 1469-1480

66M. Bleich and R. Warth (2000) The very small-conductance K+ channel KVLQT1 and epithelial function. Pflugers Archiv European Journal of Physiology 440, 202-206

68L.J. Manderfield and A.L. George Jr (2008) KCNE4 can co-associate with the I(Ks) (KCNQ1-KCNE1) channel complex. FEBS Journal 275, 1336-1349

69M. Grunnet (2002) KCNE4 is an inhibitory subunit to the KCNQ1 channel. Journal of Physiology 542, 119-130

70S. Bendahhou (2005) In vitro molecular interactions and distribution of KCNE family with KCNQ1 in the human heart. Cardiovascular Research 67, 529-538

71L.S. Ravn (2008) Gain of function in IKs secondary to a mutation in KCNE5 associated with atrial fibrillation. Heart Rhythm 5, 427-435

72N. Tinel (2000) KCNE2 confers background current characteristics to the cardiac KCNQ1 potassium channel. EMBO Journal 19, 6326-6330

73A. Lundby (2007) KCNQ1 mutation Q147R is associated with atrial fibrillation and prolonged QT interval. Heart Rhythm 4, 1532-1541

74M.C. Sanguinetti (1995) A mechanistic link between an inherited and an acquired cardiac arrhythmia: HERG encodes the IKr potassium channel. Cell 81, 299-307

75M.C. Trudeau (1995) HERG, a human inward rectifier in the voltage-gated potassium channel family. Science 269, 92-95

76P.S. Spector (1996) Class III antiarrhythmic drugs block HERG, a human cardiac delayed rectifier K+ channel – open-channel block by methanesulfonanilides. Circulation Research 78, 499-503

77Y. Lu (2003) Mutant MiRP1 subunits modulate HERG K+ channel gating: a mechanism for pro-arrhythmia in long QT syndrome type 6. Journal of Physiology 551, 253-262

78M. Weerapura (2002) A comparison of currents carried by HERG, with and without coexpression of MiRP1, and the native rapid delayed rectifier current. Is MiRP1 the missing link? Journal of Physiology 540, 15-27

79R. Mazhari (2001) Molecular interactions between two long-QT syndrome gene products, HERG and KCNE2, rationalised by in vitro and in silico analysis. Circulation Research 89, 33-38

80H. Sale (2008) Physiological properties of hERG 1a/1b heteromeric currents and a hERG 1b-specific mutation associated with Long-QT syndrome. Circulation Research 103, e81-e95

81A.P. Larsen (2008) Characterization of hERG1a and hERG1b potassium channels – a possible role for hERG1b in the I (Kr) current. Pflugers Archiv 456, 1137-1148

82A.L. Pond (2000) Expression of distinct ERG proteins in rat, mouse, and human heart. Relation to functional I(Kr) channels. Journal of Biological Chemistry 275, 5997-6006

83M. Pourrier (2003) Canine ventricular KCNE2 expression resides predominantly in Purkinje fibers. Circulation Research 93, 189-191

84M. Jiang (2004) KCNE2 protein is expressed in ventricles of different species, and changes in its expression contribute to electrical remodeling in diseased hearts. Circulation 109, 1783-1788

85E. Gordon (2008) A KCNE2 mutation in a patient with cardiac arrhythmia induced by auditory stimuli and serum electrolyte imbalance. Cardiovascular Research 77, 98-106

86D. Isbrandt (2002) Identification and functional characterization of a novel KCNE2 (MiRP1) mutation that alters HERG channel kinetics. Journal of Molecular Medicine 80, 524-532

88M.C. Sanguinetti (1996) Spectrum of HERG K+-channel dysfunction in an inherited cardiac arrhythmia. Proceedings of the National Academy of Sciences of the United States of America 93, 2208-2212

89M.J. Ackerman (2003) Ethnic differences in cardiac potassium channel variants: implications for genetic susceptibility to sudden cardiac death and genetic testing for congenital long QT syndrome. Mayo Clinic Proceedings 78, 1479-1487

90G. Szabo (2005) Asymmetrical distribution of ion channels in canine and human left-ventricular wall: epicardium versus midmyocardium. Pflugers Archiv 450, 307-316

91N. Szentadrassy (2005) Apico-basal inhomogeneity in distribution of ion channels in canine and human ventricular myocardium. Cardiovascular Research 65, 851-860

92P. Melnyk (2005) Comparison of ion channel distribution and expression in cardiomyocytes of canine pulmonary veins versus left atrium. Cardiovascular Research 65, 104-116

93S.Y. Um and T.V. McDonald (2007) Differential association between HERG and KCNE1 or KCNE2. PLoS One 2, e933-

94T.V. McDonald (1997) A minK-HERG complex regulates the cardiac potassium current IKr. Nature 388, 289-292

95L. Bianchi (1999) Cellular dysfunction of LQT5-minK mutants: abnormalities of IKs, IKr and trafficking in long QT syndrome. Human Molecular Genetics 8, 1499-1507

96H. Ohyama (2001) Inhibition of cardiac delayed rectifier K+ currents by an antisense oligodeoxynucleotide against IsK (minK) and over-expression of IsK mutant D77N in neonatal mouse hearts. Pflugers Archiv European Journal of Physiology 442, 329-335

97T. Yang , S. Kupershmidt and D.M. Roden (1995) Anti-minK antisense decreases the amplitude of the rapidly activating cardiac delayed rectifier K+ current. Circulation Research 77, 1246-1253

98M.R. Finley (2002) Expression and coassociation of ERG1, KCNQ1, and KCNE1 potassium channel proteins in horse heart. American Journal of Physiology. Heart and Circulatory Physiology 283, H126-H138

99J.E. Dixon (1996) Role of the Kv4.3K+ channel in ventricular muscle – a molecular correlate for the transient outward current. Circulation Research 79, 659-668

101S.P. Patel and D.L. Campbell (2005) Transient outward potassium current, ‘Ito’, phenotypes in the mammalian left ventricle: underlying molecular, cellular and biophysical mechanisms. Journal of Physiology 569, 7-39

102N. Niwa and J.M. Nerbonne (2010) Molecular determinants of cardiac transient outward potassium current (I(to)) expression and regulation. Journal of Molecular and Cellular Cardiology 48, 12-25

103J.L. Greenstein (2000) Role of the calcium-independent transient outward current Ito1 in shaping action potential morphology and duration. Circulation Research 87, 1026-1033

104M. Nabauer (1996) Regional differences in current density and rate-dependent properties of the transient outward current in subepicardial and subendocardial myocytes of human left ventricle. Circulation 93, 168-177

105E. Wettwer (1994) Transient outward current in human ventricular myocytes of subepicardial and subendocardial origin. Circulation Research 75, 473-482

106W.F. An (2000) Modulation of A-type potassium channels by a family of calcium sensors. Nature 403, 553-556

107W.N. Guo (2002) Role of heteromultimers in the generation of myocardial transient outward K+ currents. Circulation Research 90, 586-593

108B. Rosati (2001) Regulation of KChIP2 potassium channel β subunit gene expression underlies the gradient of transient outward current in canine and human ventricle. Journal of Physiology 533, 119-125

109I. Deschenes (2002) Regulation of Kv4.3 current by KChIP2 splice variants – a component of native cardiac Ito? Circulation 106, 423-429

110S. Radicke (2006) Functional modulation of the transient outward current Ito by KCNE beta-subunits and regional distribution in human non-failing and failing hearts. Cardiovascular Research 71, 695-703

112E.K. Yang (2001) Kvβ subunits increase expression of Kv4.3 channels by interacting with their C termini. Journal of Biological Chemistry 276, 4839-4844

113I. Deschênes and G.F. Tomaselli (2002) Modulation of Kv4.3 current by accessory subunits. FEBS Letters 528, 183-188

114M.S. Nadal (2003) The CD26-related dipeptidyl aminopeptidase-like protein DPPX is a critical component of neuronal A-type K+ channels. Neuron 37, 449-461

115J. Wu (2010) KCNE2 modulation of Kv4.3 current and its potential role in fatal rhythm disorders. Heart Rhythm 7, 199-205

116A. Lundby and S.P. Olesen (2006) KCNE3 is an inhibitory subunit of the Kv4.3 potassium channel. Biochemical and Biophysical Research Communications 346, 958-967

118J.R. Giudicessi (2011) Transient outward current (I(to)) gain-of-function mutations in the KCND3-encoded Kv4.3 potassium channel and Brugada syndrome. Heart Rhythm 8, 1024-1032

119S. Radicke (2008) Effects of MiRP1 and DPP6 beta-subunits on the blockade induced by flecainide of Kv4.3/KChIP2 channels. British Journal of Pharmacology 154, 774-786

120X. Ren (2005) Transmembrane interaction mediates complex formation between peptidase homologues and Kv4 channels. Molecular and Cellular Neurosciences 29, 320-332

121H.L. Li (2006) DPP10 is an inactivation modulatory protein of Kv4.3 and Kv1.4. American Journal of Physiology. Cell Physiology 291, C966-C976

122S. Radicke (2005) Expression and function of dipeptidyl-aminopeptidase-like protein 6 as a putative beta-subunit of human cardiac transient outward current encoded by Kv4.3. Journal of Physiology 565, 751-756

123P.G. Postema (2011) Founder mutations in the Netherlands: familial idiopathic ventricular fibrillation and DPP6. Netherlands Heart Journal 19, 290-296

124S. Radicke (2009) The transmembrane beta-subunits KCNE1, KCNE2, and DPP6 modify pharmacological effects of the antiarrhythmic agent tedisamil on the transient outward current Ito. Naunyn-Schmiedebergs Archives of Pharmacology 379, 617-626

125T.K. Roepke (2008) Targeted deletion of kcne2 impairs ventricular repolarization via disruption of I(K,slow1) and I(to,f). FASEB Journal 22, 3648-3660

126C. Marionneau , R.R. Townsend and J.M. Nerbonne (2011) Proteomic analysis highlights the molecular complexities of native Kv4 channel macromolecular complexes. Seminars in Cell and Developmental Biology 22, 145-152

127O. Monfredi (2010) The anatomy and physiology of the sinoatrial node – a contemporary review. Pacing and Clinical Electrophysiology 33, 1392-1406

128A. Ludwig (1999) Two pacemaker channels from human heart with profoundly different activation kinetics. EMBO Journal 18, 2323-2329

129N.J. Chandler (2009) Molecular architecture of the human sinus node: insights into the function of the cardiac pacemaker. Circulation 119, 1562-1575

130B. Ye and J.M. Nerbonne (2009) Proteolytic processing of HCN2 and co-assembly with HCN4 in the generation of cardiac pacemaker channels. Journal of Biological Chemistry 284, 25553-25559

131M. Biel (2009) Hyperpolarization-activated cation channels: from genes to function. Physiological Reviews 89, 847-885

132C. Altomare (2003) Heteromeric HCN1–HCN4 channels: a comparison with native pacemaker channels from the rabbit sinoatrial node. Journal of Physiology 549, 347-359

133M.C. Brandt (2009) Effects of KCNE2 on HCN isoforms: distinct modulation of membrane expression and single channel properties. American Journal of Physiology. Heart and Circulatory Physiology 297, H355-H363

134J. Qu (2004) MiRP1 modulates HCN2 channel expression and gating in cardiac myocytes. Journal of Biological Chemistry 279, 43497-43502

135D.R. Van Wagoner (1997) Outward K+ current densities and Kv1.5 expression are reduced in chronic human atrial fibrillation. Circulation Research 80, 772-781

136B. Ordog (2006) Gene expression profiling of human cardiac potassium and sodium channels. International Journal of Cardiology 111, 386-393

137D.J. Tester (2010) Prevalence and spectrum of large deletions or duplications in the major long QT syndrome-susceptibility genes and implications for long QT syndrome genetic testing. American Journal of Cardiology 106, 1124-1128

139L. Crotti (2009) A KCNH2 branch point mutation causing aberrant splicing contributes to an explanation of genotype-negative long QT syndrome. Heart Rhythm 6, 212-218

140Z.A. Bhuiyan (2008) An intronic mutation leading to incomplete skipping of exon-2 in KCNQ1 rescues hearing in Jervell and Lange-Nielsen syndrome. Progress in Biophysics and Molecular Biology 98, 319-327

141L. Zhang (2004) An intronic mutation causes long QT syndrome. Journal of the American College of Cardiology 44, 1283-1291

143I. Splawski (1997) Mutations in the hminK gene cause long QT syndrome and suppress IKs function. Nature Genetics 17, 338-340

144C. Napolitano (2005) Genetic testing in the long QT syndrome: development and validation of an efficient approach to genotyping in clinical practice. Journal of the American Medical Association 294, 2975-2980

145T.K. Roepke (2009) Kcne2 deletion uncovers its crucial role in thyroid hormone biosynthesis. Nature Medicine 15, 1186-1194

146K. Purtell , T.K. Roepke and G.W. Abbott (2010) Cardiac arrhythmia and thyroid dysfunction: a novel genetic link. International Journal of Biochemistry and Cell Biology 42, 1767-1770

147S. Viskin (2003) Long QT syndrome caused by noncardiac drugs. Progress in Cardiovascular Diseases 45, 415-427

149X.H. Wehrens (2002) Novel insights in the congenital long QT syndrome. Annals of Internal Medicine 137, 981-992

150P.J. Schwartz (2011) Pharmacological and non-pharmacological management of the congenital long QT syndrome: the rationale. Pharmacology and Therapeutics 131, 171-177

151Q. Wang (1996) Positional cloning of a novel potassium channel gene: KVLQT1 mutations cause cardiac arrhythmias. Nature Genetics 12, 17-23

152M.E. Curran (1995) A molecular basis for cardiac arrhythmia: HERG mutations cause long QT syndrome. Cell 80, 795-803

153Q. Wang (1995) SCN5A mutations associated with an inherited cardiac arrhythmia, long QT syndrome. Cell 80, 805-811

155N.M. Plaster (2001) Mutations in Kir2.1 cause the developmental and episodic electrical phenotypes of Andersen's syndrome. Cell 105, 511-519

156I. Splawski (2004) Ca(V)1.2 calcium channel dysfunction causes a multisystem disorder including arrhythmia and autism. Cell 119, 19-31

157K. Ueda (2008) Syntrophin mutation associated with long QT syndrome through activation of the nNOS-SCN5A macromolecular complex. Proceedings of the National Academy of Sciences of the United States of America 105, 9355-9360

158J. Cui (2001) Analysis of the cyclic nucleotide binding domain of the HERG potassium channel and interactions with KCNE2. Journal of Biological Chemistry 276, 17244-17251

159A. Aydin (2005) Single nucleotide polymorphism map of five long-QT genes. Journal of Molecular Medicine 83, 159-165

160F. Sesti (2000) A common polymorphism associated with antibiotic-induced cardiac arrhythmia. Proceedings of the National Academy of Sciences of the United States of America 97, 10613-10618

161A.D. Paulussen (2004) Genetic variations of KCNQ1, KCNH2, SCN5A, KCNE1, and KCNE2 in drug-induced long QT syndrome patients. Journal of Molecular Medicine 82, 182-188

162Y. Yang (2004) Identification of a KCNE2 gain-of-function mutation in patients with familial atrial fibrillation. American Journal of Human Genetics 75, 899-905

163G. Millat (2006) Spectrum of pathogenic mutations and associated polymorphisms in a cohort of 44 unrelated patients with long QT syndrome. Clinical Genetics 70, 214-227

164F.T. Wegener , J.R. Ehrlich and S.H. Hohnloser (2008) Amiodarone-associated macroscopic T-wave alternans and torsade de pointes unmasking the inherited long QT syndrome. Europace 10, 112-113

165M.T. Keating and M.C. Sanguinetti (2001) Molecular and cellular mechanisms of cardiac arrhythmias. Cell 104, 569-580

166S.B. Long , E.B. Campbell and R. MacKinnon (2005) Voltage sensor of Kv1.2: structural basis of electromechanical coupling. Science 309, 903-908

E.S. Kaufman (2011) Arrhythmic risk in congenital long QT syndrome. Journal of Electrocardiology 44, 645-649

O. Pongs and J.R. Schwarz (2010) Ancillary subunits associated with voltage-dependent K+ channels. Physiological Reviews 90, 755-796

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