Arrhythmogenic KCNE gene variants: Current knowledge and future challenges

Frontiers in Genetics

Volumn 5, Issue JAN, 2014, Pages

  Crump, Shawn M ^a   Abbott, Geoffrey W ^a  

^a UNIVERSITY OF CALIFORNIA   (United States)

Author keywords

Atrial fibrillation; Brugada syndrome; Long qt syndrome; Mink related peptide; Mirp

Indexed keywords

MACROLIDE; POTASSIUM CHANNEL HERG; POTASSIUM CHANNEL KCNE1; POTASSIUM CHANNEL KCNE2; POTASSIUM CHANNEL KCNQ1; SHAL POTASSIUM CHANNEL; VOLTAGE GATED POTASSIUM CHANNEL;

ARRHYTHMOGENESIS; BRUGADA SYNDROME; CELL MIGRATION; GENE MUTATION; GENETIC VARIABILITY; HEART ARRHYTHMIA; HEART DISEASE; HEART INFARCTION; HEART REPOLARIZATION; HUMAN; JERVELL AND LANGE-NIELSEN SYNDROME; LONG QT SYNDROME; LUNG CAPACITY; REVIEW;

EID: 84893688099     PISSN: None     EISSN: 16648021     Source Type: Journal    
DOI: 10.3389/fgene.2014.00003     Document Type: Review

References (88)

1. 2 and the K (+) channel: the tail wagging the dog. Channels (Austin) 6, 1-10. doi: 10.4161/chan.19126
2. Abbott, G. W., and Goldstein, S. A. (1998). A superfamily of small potassium channel subunits: form and function of the MinK-related peptides (MiRPs). Q. Rev. Biophys. 31, 357-398. doi: 10.1017/S0033583599003467
3. 1 forms IKr potassium channels with HERG and is associated with cardiac arrhythmia. Cell 97, 175-187. doi: 10.1016/S0092-8674(00)80728-X
4. Ackerman, M. J., Tester, D. J., Jones, G. S., Will, M. L., Burrow, C. R., and Curran, M. E. (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 Clin. Proc. 78, 1479-1487. doi: 10.4065/78.12.1479
5. Ackerman, M. J., Tester, D. J., and Porter, C. J. (1999). Swimming, a gene-specific arrhythmogenic trigger for inherited long QT syndrome. Mayo Clin. Proc. 74, 1088-1094. doi: 10.4065/74.11.1088
6. 2 mutations reduce Kv11.1 (hERG) current by a class 2 (trafficking-deficient) mechanism. Circulation 113, 365-373. doi: 10.1161/CIRCULATIONAHA.105.570200
7. Angelo, K., Jespersen, T., Grunnet, M., Nielsen, M. S., Klaerke, D. A., and Olesen, S. P. (2002). KCNE5 induces time- and voltage-dependent modulation of the KCNQ1 current. Biophys. J. 83, 1997-2006. doi: 10.1016/S0006-3495(02)73961-1
8. Arrighi, I., Bloch-Faure, M., Grahammer, F., Bleich, M., Warth, R., Mengual, R., et al. (2001). Altered potassium balance and aldosterone secretion in a mouse model of human congenital long QT syndrome. Proc. Natl. Acad. Sci. U.S.A. 98, 8792-8797. doi: 10.1073/pnas.141233398
9. 1 and lsK (minK) proteins associate to form the I(Ks) cardiac potassium current. Nature 384, 78-80. doi: 10.1038/384078a0
10. Barriere, H., Rubera, I., Belfodil, R., Tauc, M., Tonnerieux, N., Poujeol, C., et al. (2003). Swelling-activated chloride and potassium conductance in primary cultures of mouse proximal tubules. Implication of KCNE1 protein. J. Membr. Biol. 193, 153-170. doi: 10.1007/s00232-003-2014-z
11. Bianchi, L., Shen, Z., Dennis, A. T., Priori, S. G., Napolitano, C., Ronchetti, E., et al. (1999). Cellular dysfunction of LQT5-minK mutants: abnormalities of IKs, IKr and trafficking in long QT syndrome. Hum. Mol. Genet. 8, 1499-1507. doi: 10.1093/hmg/8.8.1499
12. Brugada, R., Brugada, P., and Brugada, J. (2006). Electrocardiogram interpretation and class I blocker challenge in Brugada syndrome. J. Electrocardiol. 39(4 Suppl.), S115-S118. doi: 10.1016/j.jelectrocard.2006.05.014
13. Chen, H., Kim, L. A., Rajan, S., Xu, S., and Goldstein, S. A. (2003). Charybdotoxin binding in the I(Ks) pore demonstrates two MinK subunits in each channel complex. Neuron 40, 15-23. doi: 10.1016/S0896-6273(03)00570-1
14. Chen, J., Seebohm, G., and Sanguinetti, M. C. (2002). Position of aromatic residues in the S6 domain, not inactivation, dictates cisapride sensitivity of HERG and eag potassium channels. Proc. Natl. Acad. Sci. U.S.A. 99, 12461-12466. doi: 10.1073/pnas.192367299
15. Curran, M. E., Splawski, I., Timothy, K. W., Vincent, G. M., Green, E. D., and Keating, M. T. (1995). A molecular basis for cardiac arrhythmia: HERG mutations cause long QT syndrome. Cell 80, 795-803. doi: 10.1016/0092-8674(95)90358-5
16. Dedek, K., and Waldegger, S. (2001). Colocalization of KCNQ1/KCNE channel subunits in the mouse gastrointestinal tract. Pflugers Arch. 442, 896-902. doi: 10.1007/s004240100609
17. Delpon, E., Cordeiro, J. M., Nunez, L., Thomsen, P. E., Guerchicoff, A., Pollevick, G. D., et al. (2008). Functional effects of KCNE3 mutation and its role in the development of Brugada syndrome. Circ. Arrhythm. Electrophysiol. 1, 209-218. doi: 10.1161/CIRCEP.107.748103
18. Ehrlich, J. R. (2010). Cardiac delayed rectifiers-together as one? A patho-physiologically relevant interaction between IKr and IKs. Heart Rhythm 7, 981-982. doi: 10.1016/j.hrthm.2010.04.013
19. Ehrlich, J. R., Pourrier, M., Weerapura, M., Ethier, N., Marmabachi, A. M., Hebert, T. E., et al. (2004). KvLQT1 modulates the distribution and biophysical properties of HERG. A novel alpha-subunit interaction between delayed rectifier currents. J. Biol. Chem. 279, 1233-1241. doi: 10.1074/jbc. M309087200
20. Fatini, C., Sticchi, E., Genuardi, M., Sofi, F., Gensini, F., Gori, A. M., et al. (2006). Analysis of minK and eNOS genes as candidate loci for predisposition to non-valvular atrial fibrillation. Eur. Heart J. 27, 1712-1718. doi: 10.1093/eurheartj/ehl087
21. Fatini, C., Sticchi, E., Marcucci, R., Verdiani, V., Nozzoli, C., Vassallo, C., et al. (2010). S38G single-nucleotide polymorphism at the KCNE1 locus is associated with heart failure. Heart Rhythm 7, 363-367. doi: 10.1016/j.hrthm.2009.11.032
22. Freeman, L. C., and Kass, R. S. (1993). Expression of a minimal K+ channel protein in mammalian cells and immunolocalization in guinea pig heart. Circ. Res. 73, 968-973. doi: 10.1161/01.RES.73.5.968
23. Friedlander, Y., Vatta, M., Sotoodehnia, N., Sinnreich, R., Li, H., Manor, O., et al. (2005). Possible association of the human KCNE1 (minK) gene and QT interval in healthy subjects: evidence from association and linkage analyses in Israeli families. Ann. Hum. Genet. 69(Pt 6), 645-656. doi: 10.1046/j.1529-8817.2005.00182.x
24. 4 is an inhibitory subunit to the KCNQ1 channel. J. Physiol. 542(Pt 1), 119-130. doi: 10.1113/jphysiol.2002.017301
25. 1 potassium current without affecting the activation kinetics. Biochem. Biophys. Res. Commun. 328, 1146-1153. doi: 10.1016/j.bbrc.2005.01.071
26. Hu, Z., Crump, S. M., Anand, M., Kant, R., Levi, R., and Abbott, G. W. (2013). Kcne3 deletion initiates extracardiac arrhythmogenesis in mice. FASEB J. doi: 10.1096/fj.13-241828. [Epub ahead of print].
27. Hu, Z., Kant, R., Anand, M., King, E. C., Krogh-Madsen, T., Christini, D. J., et al. (2014). Kcne2 Deletion Creates a Multisystem Syndrome Predisposing to Sudden Cardiac Death. Circ. Cardiovasc. Genet. doi: 10.1161/CIRCGENETICS.113.000315. [Epub ahead of print].
28. Husser, D., Stridh, M., Sornmo, L., Roden, D. M., Darbar, D., and Bollmann, A. (2009). A genotype-dependent intermediate ECG phenotype in patients with persistent lone atrial fibrillation genotype ECG-phenotype correlation in atrial fibrillation. Circ. Arrhythm. Electrophysiol. 2, 24-28. doi: 10.1161/CIRCEP.108.799098
29. 2 protein is expressed in ventricles of different species, and changes in its expression contribute to electrical remodeling in diseased hearts. Circulation 109, 1783-1788. doi: 10.1161/01.CIR.0000124225.43852.50
30. Kanda, V. A., Purtell, K., and Abbott, G. W. (2011). Protein kinase C downregulates I(Ks) by stimulating KCNQ1-KCNE1 potassium channel endocytosis. Heart Rhythm 8, 1641-1647. doi: 10.1016/j.hrthm.2011.04.034
31. Kapplinger, J., Tester, D. J., and Ackerman, M. J. (2013). The compounding dilemma of genetic noise: identification of the genetic noise rate in genes associated with cardiac channelopathies. Heart Rhythm 10, 1752-1753. doi: 10.1016/j.hrthm.2013.09.047
32. Kathiresan, S., Voight, B. F., Purcell, S., Musunuru, K., Ardissino, D., Mannucci, P. M., et al. (2009). Genome-wide association of early-onset myocardial infarction with single nucleotide polymorphisms and copy number variants. Nat. Genet. 41, 334-341. doi: 10.1038/ng.327
33. Lai, L. P., Deng, C. L., Moss, A. J., Kass, R. S., and Liang, C. S. (1994). Polymorphism of the gene encoding a human minimal potassium ion channel (minK). Gene 151, 339-340. doi: 10.1016/0378-1119(94)90685-8
34. 2 modulates the function of Kv4.3 channel]. Nan Fang Yi Ke Da Xue Xue Bao 26, 1754-1756.
35. Loussouarn, G., Park, K. H., Bellocq, C., Baro, I., Charpentier, F., and Escande, D. (2003). Phosphatidylinositol-4,5-bisphosphate, PIP2, controls KCNQ1/KCNE1 voltage-gated potassium channels: a functional homology between voltage-gated and inward rectifier K+ channels. EMBO J. 22, 5412-5421. doi: 10.1093/emboj/cdg526
36. McCrossan, Z. A., and Abbott, G. W. (2004). The MinK-related peptides. Neuropharmacology 47, 787-821. doi: 10.1016/j.neuropharm.2004.06.018
37. 1. J. Membr. Biol. 228, 1-14. doi: 10.1007/s00232-009-9154-8
38. McDonald, T. V., Yu, Z., Ming, Z., Palma, E., Meyers, M. B., Wang, K. W., et al. (1997). A minK-HERG complex regulates the cardiac potassium current I(Kr). Nature 388, 289-292. doi: 10.1038/40882
39. Nakajima, T., Wu, J., Kaneko, Y., Ashihara, T., Ohno, S., Irie, T., et al. (2012). KCNE3 T4A as the genetic basis of Brugada-pattern electrocardiogram. Circ. J. 76, 2763-2772. doi: 10.1253/circj. CJ-12-0551
40. Nakajo, K., Ulbrich, M. H., Kubo, Y., and Isacoff, E. Y. (2010). Stoichiometry of the KCNQ1-KCNE1 ion channel complex. Proc. Natl. Acad. Sci. U.S.A. 107, 18862-18867. doi: 10.1073/pnas.1010354107
41. Nerbonne, J. M., Nichols, C. G., Schwarz, T. L., and Escande, D. (2001). Genetic manipulation of cardiac K(+) channel function in mice: what have we learned, and where do we go from here? Circ. Res. 89, 944-956. doi: 10.1161/hh2301.100349
42. Niwa, N., and Nerbonne, J. M. (2010). Molecular determinants of cardiac transient outward potassium current (I(to)) expression and regulation. J. Mol. Cell. Cardiol. 48, 12-25. doi: 10.1016/j.yjmcc.2009.07.013
43. 3 mutation reduces repolarizing potassium current and associated with long QT syndrome. Hum. Mutat. 30, 557-563. doi: 10.1002/humu.20834
44. 1L) variants are novel modulators of Brugada syndrome and idiopathic ventricular fibrillation. Circ. Arrhythm. Electrophysiol. 4, 352-361. doi: 10.1161/CIRCEP.110.959619
45. Park, K. H., Kwok, S. M., Sharon, C., Baerga, R., and Sesti, F. (2003). N-Glycosylation-dependent block is a novel mechanism for drug-induced cardiac arrhythmia. FASEB J. 17, 2308-2309. doi: 10.1096/fj.03-0577fje
46. 3 reveals an important role in intestinal and tracheal Cl- transport. J. Biol. Chem. 285, 7165-7175. doi: 10.1074/jbc. M109.047829
47. Prystupa, A., Dzida, G., Myslinski, W., Malaj, G., and Lorenc, T. (2006). MinK gene polymorphism in the pathogenesis of lone atrial fibrillation. Kardiol. Pol. 64, 1205-1211; discussion 1212-1203.
48. Radicke, S., Cotella, D., Graf, E. M., Banse, U., Jost, N., Varro, A., et al. (2006). Functional modulation of the transient outward current Ito by KCNE beta-subunits and regional distribution in human non-failing and failing hearts. Cardiovasc. Res. 71, 695-703. doi: 10.1016/j.cardiores.2006.06.017
49. 2, and DPP6 modify pharmacological effects of the antiarrhythmic agent tedisamil on the transient outward current Ito. Naunyn Schmiedebergs Arch. Pharmacol. 379, 617-626. doi: 10.1007/s00210-008-0389-1
50. Radicke, S., Riedel, T., Cotella, D., Turnow, K., Ravens, U., Schaefer, M., et al. (2013). Accessory subunits alter the temperature sensitivity of Kv4.3 channel complexes. J. Mol. Cell. Cardiol. 56, 8-18. doi: 10.1016/j.yjmcc.2012.12.017
51. 2 channels. Br. J. Pharmacol. 154, 774-786. doi: 10.1038/bjp.2008.134
52. Ravn, L. S., Aizawa, Y., Pollevick, G. D., Hofman-Bang, J., Cordeiro, J. M., Dixen, U., et al. (2008). Gain of function in IKs secondary to a mutation in KCNE5 associated with atrial fibrillation. Heart Rhythm 5, 427-435. doi: 10.1016/j.hrthm.2007.12.019
53. 5 to risk of atrial fibrillation. Am. J. Cardiol. 96, 405-407. doi: 10.1016/j.amjcard.2005.03.086
54. Ren, X. Q., Liu, G. X., Organ-Darling, L. E., Zheng, R., Roder, K., Jindal, H. K., et al. (2010). Pore mutants of HERG and KvLQT1 downregulate the reciprocal currents in stable cell lines. Am. J. Physiol. Heart Circ. Physiol. 299, H1525-H1534. doi: 10.1152/ajpheart.00479.2009
55. Rivas, A., and Francis, H. W. (2005). Inner ear abnormalities in a Kcnq1 (Kvlqt1) knockout mouse: a model of Jervell and Lange-Nielsen syndrome. Otol. Neurotol. 26, 415-424. doi: 10.1097/01.mao.0000169764.00798.84
56. 2 potassium channel ancillary subunit is essential for gastric acid secretion. J. Biol. Chem. 281, 23740-23747. doi: 10.1074/jbc. M604155200
57. 2 forms potassium channels with KCNA3 and KCNQ1 in the choroid plexus epithelium. FASEB J. 25, 4264-4273. doi: 10.1096/fj.11-187609
58. Roepke, T. K., King, E. C., Purtell, K., Kanda, V. A., Lerner, D. J., and Abbott, G. W. (2011b). Genetic dissection reveals unexpected influence of beta subunits on KCNQ1 K+ channel polarized trafficking in vivo. FASEB J. 25, 727-736. doi: 10.1096/fj.10-173682
59. Roepke, T. K., King, E. C., Reyna-Neyra, A., Paroder, M., Purtell, K., Koba, W., et al. (2009). Kcne2 deletion uncovers its crucial role in thyroid hormone biosynthesis. Nat. Med. 15, 1186-1194. doi: 10.1038/nm.2029
60. Roepke, T. K., Kontogeorgis, A., Ovanez, C., Xu, X., Young, J. B., Purtell, K., et al. (2008). Targeted deletion of kcne2 impairs ventricular repolarization via disruption of I(K, slow1) and I(to, f). FASEB J. 22, 3648-3660. doi: 10.1096/fj.08-110171
61. 1 and minK (IsK) proteins to form cardiac I(Ks) potassium channel. Nature 384, 80-83. doi: 10.1038/384080a0
62. Sanguinetti, M. C., Jiang, C., Curran, M. E., and Keating, M. T. (1995). A mechanistic link between an inherited and an acquired cardiac arrhythmia: HERG encodes the IKr potassium channel. Cell 81, 299-307. doi: 10.1016/0092-8674(95)90340-2
63. Sanguinetti, M. C., and Jurkiewicz, N. K. (1990). Two components of cardiac delayed rectifier K+ current. Differential sensitivity to block by class III antiarrhythmic agents. J. Gen. Physiol. 96, 195-215. doi: 10.1085/jgp.96.1.195
64. 3. Nature 403, 196-199. doi: 10.1038/35003200
65. 1 mutations cause jervell and Lange-Nielsen syndrome. Nat. Genet. 17, 267-268. doi: 10.1038/ng1197-267
66. Sesti, F., Abbott, G. W., Wei, J., Murray, K. T., Saksena, S., Schwartz, P. J., et al. (2000). A common polymorphism associated with antibiotic-induced cardiac arrhythmia. Proc. Natl. Acad. Sci. U.S.A. 97, 10613-10618. doi: 10.1073/pnas.180223197
67. Sesti, F., and Goldstein, S. A. (1998). Single-channel characteristics of wild-type IKs channels and channels formed with two minK mutants that cause long QT syndrome. J. Gen. Physiol. 112, 651-663. doi: 10.1085/jgp.112.6.651
68. Silva, J., and Rudy, Y. (2005). Subunit interaction determines IKs participation in cardiac repolarization and repolarization reserve. Circulation 112, 1384-1391. doi: 10.1161/CIRCULATIONAHA.105.543306
69. Smith, P. L., Baukrowitz, T., and Yellen, G. (1996). The inward rectification mechanism of the HERG cardiac potassium channel. Nature 379, 833-836. doi: 10.1038/379833a0
70. Soler Artigas, M., Loth, D. W., Wain, L. V., Gharib, S. A., Obeidat, M., Tang, W., et al. (2011). Genome-wide association and large-scale follow up identifies 16 new loci influencing lung function. Nat. Genet. 43, 1082-1090. doi: 10.1038/ng.941
71. Splawski, I., Tristani-Firouzi, M., Lehmann, M. H., Sanguinetti, M. C., and Keating, M. T. (1997). Mutations in the hminK gene cause long QT syndrome and suppress IKs function. Nat. Genet. 17, 338-340. doi: 10.1038/ng1197-338
72. Takumi, T., Ohkubo, H., and Nakanishi, S. (1988). Cloning of a membrane protein that induces a slow voltage-gated potassium current. Science 242, 1042-1045. doi: 10.1126/science.3194754
73. 1-null mice. Circ. Res. 97, 62-69. doi: 10.1161/01.RES.0000173047.42236.88
74. 2 confers background current characteristics to the cardiac KCNQ1 potassium channel. EMBO J. 19, 6326-6330. doi: 10.1093/emboj/19.23.6326
75. 1: mutation in either of the two subunits of the slow component of the delayed rectifier potassium channel can cause Jervell and Lange-Nielsen syndrome. Hum. Mol. Genet. 6, 2179-2185. doi: 10.1093/hmg/6.12.2179
76. Vetter, D. E., Mann, J. R., Wangemann, P., Liu, J., McLaughlin, K. J., Lesage, F., et al. (1996). Inner ear defects induced by null mutation of the isk gene. Neuron 17, 1251-1264. doi: 10.1016/S0896-6273(00)80255-X
77. 1 mutations cause cardiac arrhythmias. Nat. Genet. 12, 17-23. doi: 10.1038/ng0196-17
78. Wangemann, P., Liu, J., Shen, Z., Shipley, A., and Marcus, D. C. (1995). Hypo-osmotic challenge stimulates transepithelial K+ secretion and activates apical IsK channel in vestibular dark cells. J. Membr. Biol. 147, 263-273. doi: 10.1007/BF00234524
79. Wangemann, P., Shen, Z., and Liu, J. (1996). K(+)-induced stimulation of K+ secretion involves activation of the IsK channel in vestibular dark cells. Hear. Res. 100, 201-210. doi: 10.1016/0378-5955(96)00127-X
80. 1 in cardiac myocytes and may function as a negative modulator of I(Ks) current amplitude in the heart. Heart Rhythm 3, 1469-1480. doi: 10.1016/j.hrthm.2006.08.019
81. 2 modulation of Kv4.3 current and its potential role in fatal rhythm disorders. Heart Rhythm 7, 199-205. doi: 10.1016/j.hrthm.2009.10.012
82. Xu, L. X., Yang, W. Y., Zhang, H. Q., Tao, Z. H., and Duan, C. C. (2008). [Study on the correlation between CETP TaqIB, KCNE1 S38G and eNOS T-786C gene polymorphisms for predisposition and non-valvular atrial fibrillation]. Zhonghua Liu Xing Bing Xue Za Zhi 29, 486-492.
83. 2 gain-of-function mutation in patients with familial atrial fibrillation. Am. J. Hum. Genet. 75, 899-905. doi: 10.1086/425342
84. Yu, H., Lin, Z., Mattmann, M. E., Zou, B., Terrenoire, C., Zhang, H., et al. (2013). Dynamic subunit stoichiometry confers a progressive continuum of pharmacological sensitivity by KCNQ potassium channels. Proc. Natl. Acad. Sci. U.S.A. 110, 8732-8737. doi: 10.1073/pnas.1300684110
85. Zeng, Z., Tan, C., Teng, S., Chen, J., Su, S., Zhou, X., et al. (2007). The single nucleotide polymorphisms of I(Ks) potassium channel genes and their association with atrial fibrillation in a Chinese population. Cardiology 108, 97-103. doi: 10.1159/000095943
86. Zhang, D. F., Liang, B., Lin, J., Liu, B., Zhou, Q. S., and Yang, Y. Q. (2005). [KCNE3 R53H substitution in familial atrial fibrillation]. Chin. Med. J. (Engl) 118, 1735-1738.
87. Zhang, M., Jiang, M., and Tseng, G. N. (2001). minK-related peptide 1 associates with Kv4.2 and modulates its gating function: potential role as beta subunit of cardiac transient outward channel? Circ. Res. 88, 1012-1019. doi: 10.1161/hh1001.090839
88. 2 protein is more abundant in ventricles than in atria and can accelerate hERG protein degradation in a phosphorylation-dependent manner. Am. J. Physiol. Heart Circ. Physiol. 302, H910-H922. doi: 10.1152/ajpheart.00691.2011