Modification by KCNE1 variants of the hERG potassium channel response to premature stimulation and to pharmacological inhibition

Physiological Reports

Volumn 1, Issue 6, 2013, Pages 1-15

  Du, Chunyun ^a   Harchi, Aziza El ^a   Zhang, Henggui ^b   Hancox, Jules C ^a  

^a UNIVERSITY OF BRISTOL   (United Kingdom)

^b UNIVERSITY OF MANCHESTER   (United Kingdom)

Author keywords

Cardiac; Cisapride; Clarithromycin; HERG; KCNE1; Long QT; Potassium channels; QT interval; Quinidine

Indexed keywords

CISAPRIDE; CLARITHROMYCIN; MEMBRANE PROTEIN; POTASSIUM CHANNEL HERG; POTASSIUM CHANNEL KCNE2; QUINIDINE;

ACTION POTENTIAL; ARTICLE; CONTROLLED STUDY; ELECTROPHYSIOLOGY; ELECTROSTIMULATION; GENE MUTATION; GENETIC POLYMORPHISM; GENETIC TRANSFECTION; HEART ARRHYTHMIA; HEART REPOLARIZATION; HUMAN; HUMAN CELL; IC50; LONG QT SYNDROME; MEMBRANE POTENTIAL; PROTEIN EXPRESSION;

EID: 85008946252     PISSN: None     EISSN: 2051817X     Source Type: Journal    
DOI: 10.1002/phy2.175     Document Type: Article

References (65)

1. Abbott, G. W., F. Sesti, I. Splawski, M. Buck, M. H. Lehmann, K. W. Timothy, et al. 1999. MiRP1 forms IKr potassium channels with HERG and is associated with cardiac arrhythmia. Cell 97: 175–187.
2. Abbott, G. W., X. Xu, and T. K. Roepke. 2007. Impact of ancillary subunits on ventricular repolarization. J. Electrocardiol. 40: S42–S46.
3. Bendahhou, S., C. Marionneau, K. Haurogne, M. M. Larroque, R. Derand, V. Szuts, et al. 2005. In vitro molecular interactions and distribution of KCNE family with KCNQ1 in the human heart. Cardiovasc. Res. 67: 529–538.
4. Bianchi, L., Z. Shen, A. T. Dennis, S. G. Priori, C. Napolitano, E. Ronchetti, 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.
5. Brugada, R., K. Hong, R. Dumaine, J. Cordeiro, F. Gaita, M. Borggrefe, et al. 2004. Sudden death associated with short-QT syndrome linked to mutations in HERG. Circulation 109: 30–35.
6. Chen, J., G. Seebohm, and M. C. Sanguinetti. 2002. Position of aromatic residues in the S6 domain, not inactivation, dictates cisapride sensitivity of HERG and eag potassium channels. Proc. Natl. Acad. Sci. USA 99: 12329–12333.
7. Du, X., D. Lu, E. D. Daharsh, A. Yao, R. Dewoody, and J. A. Yao. 2006. Dimethyl sulfoxide effects on hERG channels expressed in HEK293 cells. J. Pharmacol. Toxicol. Methods 54: 164–172.
8. Du, C. Y., I. Adeniran, H. Cheng, Y. H. Zhang, H. A. El, M. J. McPate, et al. 2010. Acidosis Impairs the Protective Role of hERG K+ Channels Against Premature Stimulation. J. Cardiovasc. Electrophysiol. 21: 1160–1169.
9. Du, C. Y., A. El Harchi, Y. H. Zhang, C. H. Orchard, and J. C. Hancox. 2011a. Pharmacological inhibition of hERG is modulated by extracellular but not intracellular acidosis. J. Cardiovasc. Electrophysiol. 22: 1163–1170.
10. Du, C. Y., El Harchi, M. J. McPate, C. H. Orchard, and J. C. Hancox. 2011b. Enhanced inhibitory effect of acidosis on hERG potassium channels that incorporate the hERG1b isoform. Biochem. Biophys. Res. Commun. 405: 222–227.
11. Duncan, R. S., J. M. Ridley, C. E. Dempsey, D. J. Leishman, J. L. Leaney, J. C. Hancox, et al. 2006. Erythromycin block of the HERG K+ channel: accessibility to F656 and Y652. Biochem. Biophys. Res. Commun. 341: 500–506.
12. Finlayson, K., H. J. Witchel, J. McCulloch, and A. Sharkey. 2004. Acquired QT interval prolongation and HERG: implications for drug discovery and development. Eur. J. Pharmacol. 500: 129–142.
13. Finley, M. R., Y. Li, F. Hua, J. Lillich, K. E. Mitchell, S. Ganta, et al. 2002. Expression and coassociation of ERG1, KCNQ1, and KCNE1 potassium channel proteins in horse heart. Am. J. Physiol. Heart Circ. Physiol. 283: H126–H138.
14. Hancox, J. C., A. J. Levi, and H. J. Witchel. 1998. Time course and voltage dependence of expressed HERG current compared with native ‘rapid’ delayed rectifier K current during the cardiac ventricular action potential. Pflugers Archiv. 436: 843–853.
15. Hancox, J. C., M. J. McPate, A. El Harchi, and Y. H. Zhang. 2008. The hERG potassium channel and hERG screening for drug-induced torsades de pointes. Pharmacol. Ther. 119: 118–132.
16. Henney, J. E. 2000. From the food and drug administration. JAMA 283: 1131.
17. Hong, K., P. Bjeerregaard, I. Gussak, and R. Brugada. 2005. Short QT syndrome and atrial fibrillation caused by mutation in KCNH2. J. Cardivasc. Electophysiol. 16: 394–396.
18. Jiang, M., M. Zhang, D. G. Tang, H. F. Clemo, J. Liu, D. Holwitt, et al. 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.
19. Kaab, S., D. C. Crawford, M. F. Sinner, E. R. Behr, P. J. Kannankeril, A. A. Wilde, et al. 2012. A large candidate gene survey identifies the KCNE1 D85N polymorphism as a possible modulator of drug-induced torsades de pointes. Circ. Cardiovasc. Genet. 5: 91–99.
20. Kapplinger, J. D., D. J. Tester, B. A. Salisbury, J. L. Carr, C. Harris-Kerr, G. D. Pollevick, et al. 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.
21. Kupershmidt, S., I. C. Yang, K. Hayashi, J. Wei, S. Chanthaphaychith, C. I. Petersen, et al. 2003. The IKr drug response is modulated by KCR1 in transfected cardiac and noncardiac cell lines. FASEB J. 17: 2263–2265.
22. Larsen, L. A., P. S. Andersen, J. Kanters, I. H. Svendsen, J. R. Jacobsen, J. Vuust, et al. 2001. Screening for mutations and polymorphisms in the genes KCNH2 and KCNE2 encoding the cardiac HERG/MiRP1 ion channel: implications for acquired and congenital long Q-T syndrome. Clin. Chem. 47: 1390–1395.
23. Lees-Miller, J. P., Y. Duan, G. Q. Teng, and H. J. Duff. 2000. Molecular determinant of high affinity dofetilide binding to HERG1 expressed in Xenopus oocytes: involvement of S6 sites. Mol. Pharmacol. 57: 367–374.
24. Lin, L., H. Horigome, N. Nishigami, S. Ohno, M. Horie, and R. Sumazaki. 2012. Drug-induced QT-interval prolongation and recurrent torsade de pointes in a child with heterotaxy syndrome and KCNE1 D85N polymorphism. J. Electrocardiol. 45: 770–773.
25. Lu, Y., M. P. MahautSmith, A. Varghese, C. L. H. Huang, P. R. Kemp, and J. I. Vandenberg. 2001. Effects of premature stimulation on HERG channels. J. Physiol. 537: 843–851.
26. Lu, Y., M. P. Mahaut-Smith, C. L. Huang, and J. I. Vandenberg. 2003. Mutant MiRP1 subunits modulate HERG K+ channel gating: a mechanism for pro-arrhythmia in long QT syndrome type 6. J. Physiol. 551: 253–262.
27. McCrossan, Z. A., and G. W. Abbott. 2004. The MinK-related peptides. Neuropharmacology 47: 787–821.
28. McDonald, T. V., Z. Yu, Z. Ming, E. Palma, M. B. Meyers, K. W. Wang, et al. 1997. A minK-HERG complex regulates the cardiac potassium current IKr. Nature 388: 289–292.
29. McPate, M. J., R. S. Duncan, J. T. Milnes, H. J. Witchel, and J. C. Hancox. 2005. The N588K-HERG K+ channel mutation in the ‘short QT syndrome’: mechanism of gain-in-function determined at 37°C. Biochem. Biophys. Res. Commun. 334: 441–449.
30. McPate, M. J., R. S. Duncan, J. C. Hancox, and H. J. Witchel. 2008. Pharmacology of the short QT syndrome N588K-hERG K+ channel mutation: differential impact on selected class I and class III antiarrhythmic drugs. Br. J. Pharmacol. 155: 957–966.
31. McPate, M. J., H. Zhang, I. Ideniran, J. M. Cordeiro, H. J. Witchel, and J. C. Hancox. 2009. Comparative effects of the short QT N588K mutation at 37°C on hERG K+ channel current during ventricular, Purkinje fibre and atrial action potentials: an action potential clamp study. J. Physiol. Pharmacol. 60: 23–41.
32. Milnes, J. T., H. J. Witchel, J. L. Leaney, D. J. Leishman, and J. C. Hancox. 2010. Investigating dynamic protocol-dependence of hERG potassium channel inhibition at 37 degrees C: cisapride versus dofetilide. J. Pharmacol. Toxicol. Methods 61: 178–191.
33. Mitcheson, J. S., J. Chen, M. Lin, C. Culberson, and M. C. Sanguinetti. 2000. A structural basis for drug-induced long QT syndrome. Proc. Natl. Acad. Sci. USA 97: 12329–12333.
34. Modell, S. M., and M. H. Lehmann. 2006. The long QT syndrome family of cardiac ion channelopathies: a HuGE review. Genet. Med. 8: 143–155.
35. Myokai, T., S. Ryu, H. Shimizu, and S. Oiki. 2008. Topological mapping of the asymmetric drug binding to the human ether-a-go-go-related gene product (HERG) potassium channel by use of tandem dimers. Mol. Pharmacol. 73: 1643–1651.
36. Nakajima, T., K. Hayashi, P. C. Viswanathan, M. Y. Kim, M. Anghelescu, K. A. Barksdale, et al. 2007. HERG is protected from pharmacological block by alpha-1, 2-glucosyltransferase function. J. Biol. Chem. 282: 5506–5513.
37. Nielsen, N. H., B. G. Winkel, J. K. Kanters, N. Schmitt, J. Hofman-Bang, H. S. Jensen, et al. 2007. Mutations in the Kv1.5 channel gene KCNA5 in cardiac arrest patients. Biochem. Biophys. Res. Commun. 354: 776–782.
38. Nishio, Y., T. Makiyama, H. Itoh, T. Sakaguchi, S. Ohno, Y. Z. Gong, et al. 2009. D85N, a KCNE1 polymorphism, is a disease-causing gene variant in long QT syndrome. J. Am. Coll. Cardiol. 54: 812–819.
39. Nof, E., H. Barajas-Martinez, M. Eldar, J. Urrutia, G. Caceres, G. Rosenfeld, et al. 2011. LQT5 masquerading as LQT2: a dominant negative effect of KCNE1-D85N rare polymorphism on KCNH2 current. Europace 13: 1478–1483.
40. Ohno, S., D. P. Zankov, H. Yoshida, K. Tsuji, T. Makiyama, H. Itoh, et al. 2007. N-and C-terminal KCNE1 mutations cause distinct phenotypes of long QT syndrome. Heart Rhythm 4: 332–340.
41. Ohyama, H., H. Kajita, K. Omori, T. Takumi, N. Hiramoto, T. Iwasaka, et al. 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 Arch. 442: 329–335.
42. Paulussen, A. D., R. A. Gilissen, M. Armstrong, P. A. Doevendans, P. Verhasselt, H. J. Smeets, et al. 2004. Genetic variations of KCNQ1, KCNH2, SCN5A, KCNE1, and KCNE2 in drug-induced long QT syndrome patients. J. Mol. Med. (Berl.) 82: 182–188.
43. Perrin, M. J., P. W. Kuchel, T. J. Campbell, and J. I. Vandenberg. 2008. Drug binding to the inactivated state is necessary but not sufficient for high-affinity binding to human ether-á-go-go-related gene channels. Mol. Pharmacol. 74: 1443–1452.
44. Pourrier, M., S. Zicha, J. Ehrlich, W. Han, and S. Nattel. 2003. Canine ventricular KCNE2 expression resides predominantly in Purkinje fibers. Circ. Res. 93: 189–191.
45. Roden, D. M. 2008. Repolarization reserve: a moving target. Circulation 118: 981–982.
46. Roepke, T. K., A. Kontogeorgis, C. Ovanez, X. Xu, J. B. Young, K. Purtell, 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.
47. Sanchez-Chapula, J. A., T. Ferrer, R. A. Navarro-Polanco, and M. C. Sanguinetti. 2003. Voltage-dependent profile of human ether-a-go-go-related gene channel block is influenced by a single residue in the S6 transmembrane domain. Mol. Pharmacol. 63: 1051–1058.
48. Sanguinetti, M. C., and M. Tristani-Firouzi. 2006. hERG potassium channels and cardiac arrhythmia. Nature 440: 463–469.
49. Sanguinetti, M. C., J. Chen, D. Fernandez, K. Kamiya, J. Mitcheson, and J. A. Sanchez-Chapula. 2005. Physicochemical basis for binding and voltage-dependent block of hERG channels by structurally diverse drugs. Novartis Found. Symp. 266: 159–166.
50. Sesti, F., G. W. Abbott, J. Wei, K. T. Murray, S. Saksena, P. J. Schwartz, et al. 2000. A common polymorphism associated with antibiotic-induced cardiac arrhythmia. Proc. Natl. Acad. Sci. USA 97: 10613–10618.
51. Sun, Y., X. Q. Quan, S. Fromme, R. H. Cox, P. Zhang, L. Zhang, et al. 2011. A novel mutation in the KCNH2 gene associated with short QT syndrome. J. Mol. Cell. Cardiol. 50: 433–441.
52. Tamargo, J., R. Caballero, R. Gomez, C. Valenzuela, and E. Delpon. 2004. Pharmacology of cardiac potassium channels. Cardiovasc. Res. 62: 9–33.
53. ten Tusscher, K. H., D. Noble, P. J. Noble, and A. V. Panfilov. 2004. A model for human ventricular tissue. Am. J. Physiol. Heart Circ. Physiol. 286: H1573–H1589.
54. Um, S. Y., and T. V. McDonald. 2007. Differential association between HERG and KCNE1 or KCNE2. PLoS ONE 2: e933.
55. Vandenberg, J. I., B. D. Walker, and T. J. Campbell. 2001. HERG K+ channels: friend and foe. Trends Pharmacol. Sci. 22: 240–246.
56. Viskin, S., D. Justo, A. Halkin, and D. Zeltser. 2003. Long QT syndrome caused by noncardiac drugs. Prog. Cardiovasc. Dis. 4 5: 415–427.
57. Volberg, W. A., B. J. Koci, W. Su, J. Lin, and J. Zhou. 2002. Blockade of human cardiac potassium channel human ether-a-go-go-related gene (HERG) by macrolide antibiotics. J. Pharmacol. Exp. Ther. 302: 320–327.
58. Walker, B. D., C. B. Singleton, J. A. Bursill, K. R. Wyse, S. M. Valenzuela, M. R. Qiu, et al. 1999. Inhibition of the human ether-a-go-go related gene (HERG) potassium channel by cisapride: affinity for open and inactivated states. Br. J. Pharmacol. 128: 444–450.
59. Weerapura, M., S. Nattel, D. Chartier, R. Caballero, and T. F. Hebert. 2002. A comparison of currents carried by HERG with and without the coexpression of MiRP1, and the native rapid delayed rectifier current. Is MiRP1 the missing link? J. Physiol. 540: 15–27.
60. Westenskow, P., I. Splawski, K. W. Timothy, M. T. Keating, and M. C. Sanguinetti. 2004. Compound mutations: a common cause of severe long-QT syndrome. Circulation 109: 1834–1841.
61. Witchel, H. J., and J. C. Hancox. 2000. Familial and acquired long QT syndrome and the cardiac rapid delayed rectifier potassium channel. Clin. Exp. Pharmacol. Physiol. 27: 753–766.
62. Yang, T., S. Kupershmidt, and D. M. Roden. 1995. Anti-minK antisense decreases the amplitude of the rapidly activating cardiac delayed rectifier K+ current. Circ. Res. 77: 1246–1253.
63. Yap, Y. G., and A. J. Camm. 2003. Drug induced QT prolongation and torsades de pointes. Heart 89: 1363–1372.
64. Zhou, Z., Q. Gong, B. Ye, Z. Fan, J. C. Makielski, G. A. Robertson, et al. 1998. Properties of HERG channels stably expressed in HEK 293 cells studied at physiological temperature. Biophys. J. 74: 230–241.
65. Zou, A., Q. P. Xu, and M. C. Sanguinetti. 1998. A mutation in the pore region of HERG K channels expressed in Xenopus oocytes reduces rectification by shifting the voltage dependence of inactivation. J. Physiol. 509: 129–137.