Current pharmacogenomic studies on hERG potassium channels

Trends in Molecular Medicine

Volumn 19, Issue 4, 2013, Pages 227-238

  He, Fa Zhong ^a   McLeod, Howard L ^b   Zhang, Wei ^a  

^a CENTRAL SOUTH UNIVERSITY   (China)

^b University of North Carolina   (United States)

Author keywords

Adverse drug reaction; HERG potassium channels; Personalized therapy; Pharmacogenomics; Polymorphism; Safety assessment

Indexed keywords

AJMALINE; AMIODARONE; AMOXAPINE; ATOMOXETINE; BEPRIDIL; CLOFILIUM; CLOMIPRAMINE; CLONAZEPAM; DESIPRAMINE; DISOPYRAMIDE; DOFETILIDE; DOXEPIN; DROPERIDOL; FLUOXETINE; IBUTILIDE; MAPROTILINE; MIANSERIN; MICONAZOLE; NIFEKALANT; POTASSIUM CHANNEL HERG; PROPAFENONE; SIBUTRAMINE; SOTALOL; TERFENADINE; THIORIDAZINE; TRAZODONE; UNINDEXED DRUG; VERAPAMIL; ZIPRASIDONE; ZONISAMIDE;

APOPTOSIS; CARDIOVASCULAR DISEASE; DISEASE PREDISPOSITION; DRUG ACTIVITY; EPILEPSY; GENE MUTATION; GENOTYPE; HUMAN; LONG QT SYNDROME; MUSCULAR DYSTROPHY; PHARMACOGENOMICS; QT INTERVAL; REVIEW; SCHIZOPHRENIA; SHORT QT SYNDROME; SINGLE NUCLEOTIDE POLYMORPHISM;

ANTI-ARRHYTHMIA AGENTS; APOPTOSIS; CARDIOVASCULAR DISEASES; DRUG EVALUATION; EPILEPSY; ETHER-A-GO-GO POTASSIUM CHANNELS; GENETIC PREDISPOSITION TO DISEASE; GENOTYPE; HUMANS; MUSCULAR DYSTROPHIES; MUTATION; NEOPLASMS; PHARMACOGENETICS; POLYMORPHISM, GENETIC; SCHIZOPHRENIA;

EID: 84875871606     PISSN: 14714914     EISSN: 1471499X     Source Type: Journal    
DOI: 10.1016/j.molmed.2012.12.006     Document Type: Review

References (110)

1. Warmke J.W., Ganetzky B. A family of potassium channel genes related to eag in Drosophila and mammals. Proc. Natl. Acad. Sci. U.S.A. 1994, 91:3438-3442.
2. Larsen A.P. Role of ERG1 isoforms in modulation of ERG1 channel trafficking and function. Pflugers Arch. 2010, 460:803-812.
3. + current highly conserved in tumors of different histogenesis: a selective advantage for cancer cells?. Cancer Res. 1998, 58:815-822.
4. Curran M.E., et al. A molecular basis for cardiac arrhythmia: HERG mutations cause long QT syndrome. Cell 1995, 80:795-803.
5. Mihic A., et al. Trafficking defect and proteasomal degradation contribute to the phenotype of a novel KCNH2 long QT syndrome mutation. PLoS ONE 2011, 6:e18273.
6. Aidery P., et al. Identification and functional characterization of the novel human ether-a-go-go-related gene (hERG) R744P mutant associated with hereditary long QT syndrome 2. Biochem. Biophys. Res. Commun. 2012, 418:830-835.
7. Krishnan Y., et al. Partially dominant mutant channel defect corresponding with intermediate LQT2 phenotype. Pacing Clin. Electrophysiol. 2012, 35:3-16.
8. Barc J., et al. Screening for copy number variation in genes associated with the long QT syndrome: clinical relevance. J. Am. Coll. Cardiol. 2011, 57:40-47.
9. Algra A., et al. QT interval variables from 24 hour electrocardiography and the two year risk of sudden death. Br. Heart J. 1993, 70:43-48.
10. Paulussen A.D., et al. Genetic variations of KCNQ1, KCNH2, SCN5A, KCNE1, and KCNE2 in drug-induced long QT syndrome patients. J. Mol. Med. (Berl.) 2004, 82:182-188.
11. + channel structure-activity relationships and mechanisms of drug-induced QT prolongation. Annu. Rev. Pharmacol. Toxicol. 2003, 43:441-461.
12. Shimizu W., Horie M. Phenotypic manifestations of mutations in genes encoding subunits of cardiac potassium channels. Circ. Res. 2011, 109:97-109.
13. Hattori T., et al. A novel gain-of-function KCNJ2 mutation associated with short-QT syndrome impairs inward rectification of Kir2.1 currents. Cardiovasc. Res. 2012, 93:666-673.
14. Hedley P.L., et al. The genetic basis of long QT and short QT syndromes: a mutation update. Hum. Mutat. 2009, 30:1486-1511.
15. Sun Y., et al. A novel mutation in the KCNH2 gene associated with short QT syndrome. J. Mol. Cell. Cardiol. 2011, 50:433-441.
16. + channel S4 domain L532P mutation: characterization at 37°C. Biochim. Biophys. Acta 2011, 1808:2477-2487.
17. + channel for a macromolecular signaling complex in acute myeloid leukemia: role in cell migration and clinical outcome. Blood 2007, 110:1238-1250.
18. Sarzani R., et al. The functional HERG variant 897T is associated with Conn's adenoma. J. Hypertens. 2006, 24:479-487.
19. Huffaker S.J., et al. A primate-specific, brain isoform of KCNH2 affects cortical physiology, cognition, neuronal repolarization and risk of schizophrenia. Nat. Med. 2009, 15:509-518.
20. Atalar F., et al. Two four-marker haplotypes on 7q36.1 region indicate that the potassium channel gene HERG1 (KCNH2, Kv11.1) is related to schizophrenia: a case control study. Behav. Brain Funct. 2010, 6:27.
21. Hashimoto R., et al. The KCNH2 gene is associated with neurocognition and the risk of schizophrenia. World J. Biol. Psychiatry 2013, 14:114-120.
22. Cockerill S.L., et al. Modulation of hERG potassium currents in HEK-293 cells by protein kinase C. Evidence for direct phosphorylation of pore forming subunits. J. Physiol. 2007, 581:479-493.
23. Hirdes W., et al. Muscarinic modulation of erg potassium current. J. Physiol. 2004, 559:67-84.
24. Gomez-Varela D., et al. Relevance of the proximal domain in the amino-terminus of HERG channels for regulation by a phospholipase C-coupled hormone receptor. FEBS Lett. 2003, 535:125-130.
25. + currents in human prolactin-secreting adenoma cells. Pflugers Arch. 2003, 445:589-600.
26. Kang P.M., Izumo S. Apoptosis and heart failure: a critical review of the literature. Circ. Res. 2000, 86:1107-1113.
27. Major cardiovascular events in hypertensive patients randomized to doxazosin vs chlorthalidone: the antihypertensive and lipid-lowering treatment to prevent heart attack trial (ALLHAT). JAMA 2000, 283:1967-1975. ALLHAT Collaborative Research Group.
28. Gonzalez-Juanatey J.R., et al. Doxazosin induces apoptosis in cardiomyocytes cultured in vitro by a mechanism that is independent of alpha1-adrenergic blockade. Circulation 2003, 107:127-131.
29. Thomas D., et al. Inhibition of human ether-a-go-go-related gene potassium channels by alpha 1-adrenoceptor antagonists prazosin, doxazosin, and terazosin. Naunyn Schmiedebergs Arch. Pharmacol. 2004, 369:462-472.
30. Wang Y.H., et al. Inhibition of the rapid component of the delayed rectifier potassium current in ventricular myocytes by angiotensin II via the AT1 receptor. Br. J. Pharmacol. 2008, 154:429-439.
31. Sanguinetti M.C. HERG1 channelopathies. Pflugers Arch. 2010, 460:265-276.
32. Omichi C., et al. Congenital long QT syndrome presenting with a history of epilepsy: misdiagnosis or relationship between channelopathies of the heart and brain?. Epilepsia 2010, 51:289-292.
33. Dai D.Z., Dai Y. Induced ion currents and the endothelin pathway as targets for anti-arrhythmic agents. Curr. Opin. Investig. Drugs 2008, 9:1001-1008.
34. + channel induces skeletal muscle atrophy by activating the ubiquitin proteasome pathway. FASEB J. 2006, 20:1531-1533.
35. Witchel H.J. Drug-induced hERG block and long QT syndrome. Cardiovasc. Ther. 2011, 29:251-259.
36. Lahti A.L., et al. Model for long QT syndrome type 2 using human iPS cells demonstrates arrhythmogenic characteristics in cell culture. Dis. Model Mech. 2011, 5:220-230.
37. Wolpert C., et al. Further insights into the effect of quinidine in short QT syndrome caused by a mutation in HERG. J. Cardiovasc. Electrophysiol. 2005, 16:54-58.
38. + channel mutation: differential impact on selected class I and class III antiarrhythmic drugs. Br. J. Pharmacol. 2008, 155:957-966.
39. + channels involved in variant 1 short QT syndrome. J. Mol. Cell. Cardiol. 2006, 41:563-566.
40. + channel deactivation through Ser631 residue interaction. Eur. J. Pharmacol. 2011, 663:59-67.
41. Etheridge S.P., et al. A new oral therapy for long QT syndrome: long-term oral potassium improves repolarization in patients with HERG mutations. J. Am. Coll. Cardiol. 2003, 42:1777-1782.
42. Harley C.A., et al. Changes in channel trafficking and protein stability caused by LQT2 mutations in the PAS domain of the HERG channel. PLoS ONE 2012, 7:e32654.
43. Delisle B.P., et al. Thapsigargin selectively rescues the trafficking defective LQT2 channels G601S and F805C. J. Biol. Chem. 2003, 278:35749-35754.
44. Yao Y., et al. Aminoglycoside antibiotics restore functional expression of truncated HERG channels produced by nonsense mutations. Heart Rhythm 2009, 6:553-560.
45. + channel long-QT2 mutations: human ether-a-go-go-related gene rescue without block. Circulation 2002, 105:2830-2835.
46. Gong Q., et al. Inhibition of nonsense-mediated mRNA decay by antisense morpholino oligonucleotides restores functional expression of hERG nonsense and frameshift mutations in long-QT syndrome. J. Mol. Cell. Cardiol. 2011, 50:223-229.
47. Ganapathi S.B., et al. State-dependent block of HERG potassium channels by R-roscovitine: implications for cancer therapy. Am. J. Physiol. Cell Physiol. 2009, 296:C701-C710.
48. + channels. Eur. J. Pharmacol. 2008, 579:98-103.
49. Parkman H.P., et al. Domperidone treatment for gastroparesis: demographic and pharmacogenetic characterization of clinical efficacy and side-effects. Dig. Dis. Sci. 2011, 56:115-124.
50. + channel: accessibility to F656 and Y652. Biochem. Biophys. Res. Commun. 2006, 341:500-506.
51. Wedam E.F., et al. QT-interval effects of methadone, levomethadyl, and buprenorphine in a randomized trial. Arch. Intern. Med. 2007, 167:2469-2475.
52. Ansermot N., et al. Substitution of (R,S)-methadone by (R)-methadone: Impact on QTc interval. Arch. Intern. Med. 2010, 170:529-536.
53. Eap C.B., et al. Stereoselective block of hERG channel by (S)-methadone and QT interval prolongation in CYP2B6 slow metabolizers. Clin. Pharmacol. Ther. 2007, 81:719-728.
54. Xing J., et al. Block effect of capsaicin on hERG potassium currents is enhanced by S6 mutation at Y652. Eur. J. Pharmacol. 2010, 630:1-9.
55. Zhang W., et al. Pharmacogenetics of drugs withdrawn from the market. Pharmacogenomics 2012, 13:223-231.
56. Perry M., et al. Structural determinants of HERG channel block by clofilium and ibutilide. Mol. Pharmacol. 2004, 66:240-249.
57. Yang P., et al. Allelic variants in long-QT disease genes in patients with drug-associated torsades de pointes. Circulation 2002, 105:1943-1948.
58. Sun Z., et al. Role of a KCNH2 polymorphism (R1047 L) in dofetilide-induced Torsades de Pointes. J. Mol. Cell. Cardiol. 2004, 37:1031-1039.
59. Ficker E., et al. Molecular determinants of dofetilide block of HERG K+ channels. Circ. Res. 1998, 82:386-395.
60. Zhang S., et al. Mechanism of block and identification of the verapamil binding domain to HERG potassium channels. Circ. Res. 1999, 84:989-998.
61. Duan J.J., et al. Verapamil blocks HERG channel by the helix residue Y652 and F656 in the S6 transmembrane domain. Acta Pharmacol. Sin. 2007, 28:959-967.
62. Witchel H.J., et al. The low-potency, voltage-dependent HERG blocker propafenone - molecular determinants and drug trapping. Mol. Pharmacol. 2004, 66:1201-1212.
63. Numaguchi H., et al. Probing the interaction between inactivation gating and Dd-sotalol block of HERG. Circ. Res. 2000, 87:1012-1018.
64. El H.A., et al. Molecular determinants of hERG potassium channel inhibition by disopyramide. J. Mol. Cell. Cardiol. 2012, 52:185-195.
65. Kiesecker C., et al. Class Ia anti-arrhythmic drug ajmaline blocks HERG potassium channels: mode of action. Naunyn Schmiedebergs Arch. Pharmacol. 2004, 370:423-435.
66. Kamiya K., et al. Molecular determinants of HERG channel block. Mol. Pharmacol. 2006, 69:1709-1716.
67. Hosaka Y., et al. Mutational analysis of block and facilitation of HERG current by a class III anti-arrhythmic agent, nifekalant. Channels (Austin) 2007, 1:198-208.
68. Ulens C., Tytgat J. Redox state dependency of HERGS631C channel pharmacology: relation to C-type inactivation. FEBS Lett. 2000, 474:111-115.
69. Kamiya K., et al. Molecular determinants of hERG channel block by terfenadine and cisapride. J. Pharmacol. Sci. 2008, 108:301-307.
70. Mitcheson J.S., et al. A structural basis for drug-induced long QT syndrome. Proc. Natl. Acad. Sci. U.S.A. 2000, 97:12329-12333.
71. Luo T., et al. Inhibition of the HERG channel by droperidol depends on channel gating and involves the S6 residue F656. Anesth. Analg. 2008, 106:1161-1170.
72. + channel blockade by the antipsychotic drug thioridazine: An obligatory role for the S6 helix residue F656. Biochem. Biophys. Res. Commun. 2006, 351:273-280.
73. Ferrer-Villada T., et al. Inhibition of cardiac HERG potassium channels by antidepressant maprotiline. Eur. J. Pharmacol. 2006, 531:1-8.
74. Scherer D., et al. Inhibition of cardiac hERG potassium channels by tetracyclic antidepressant mianserin. Naunyn Schmiedebergs Arch. Pharmacol. 2008, 378:73-83.
75. + channel block and disruption of protein trafficking by fluoxetine and norfluoxetine. Br. J. Pharmacol. 2006, 149:481-489.
76. + current inhibition, disruption of protein trafficking, and apoptosis induced by amoxapine. Naunyn Schmiedebergs Arch. Pharmacol. 2010, 381:385-400.
77. + channel by the antidepressant desipramine. Biochem. Biophys. Res. Commun. 2010, 394:536-541.
78. Duncan R.S., et al. Inhibition of the HERG potassium channel by the tricyclic antidepressant doxepin. Biochem. Pharmacol. 2007, 74:425-437.
79. Zitron E., et al. Inhibition of cardiac HERG potassium channels by the atypical antidepressant trazodone. Naunyn Schmiedebergs Arch. Pharmacol. 2004, 370:146-156.
80. + channel: accessibility to F656 and Y652. Eur. J. Pharmacol. 2008, 592:19-25.
81. + channel. Mol. Cell. Biochem. 2009, 320:125-131.
82. Su Z., et al. Block of hERG channel by ziprasidone: biophysical properties and molecular determinants. Biochem. Pharmacol. 2006, 71:278-286.
83. Scherer D., et al. Selective noradrenaline reuptake inhibitor atomoxetine directly blocks hERG currents. Br. J. Pharmacol. 2009, 156:226-236.
84. + current by antifungal drug miconazole. Br. J. Pharmacol. 2005, 144:840-848.
85. + channel by the antifungal drug ketoconazole depends on channel gating and involves the S6 residue F656. FEBS Lett. 2006, 580:1999-2005.
86. + channel blockade by the fluoroquinolone antibiotic moxifloxacin. Br. J. Pharmacol. 2006, 147:905-916.
87. + channel by direct block and disruption of protein trafficking. Eur. J. Pharmacol. 2011, 650:138-144.
88. + current in guinea pig ventricular myocytes and hERG K+ channel expressed in HEK-293 cells by fluconazole. Chin. Pharmacol. Bull. 2010, 861-866.
89. Siebrands C.C., et al. Local anesthetic interaction with human ether-a-go-go-related gene (HERG) channels: role of aromatic amino acids Y652 and F656. Anesthesiology 2005, 103:102-112.
90. Siebrands C.C., Friederich P. Inhibition of HERG channels by the local anaesthetic articaine. Eur. J. Anaesthesiol. 2007, 24:148-153.
91. + channel. J. Mol. Cell. Cardiol. 2006, 40:107-118.
92. + channels and cardiac action potential duration. Acta Pharmacol. Sin. 2011, 32:1128-1137.
93. Sakaguchi T., et al. Hydroxyzine, a first generation H(1)-receptor antagonist, inhibits human ether-a-go-go-related gene (HERG) current and causes syncope in a patient with the HERG mutation. J. Pharmacol. Sci. 2008, 108:462-471.
94. + channel. Pharmacol. Res. 2009, 60:429-437.
95. Rodriguez-Menchaca A., et al. Block of HERG channels by berberine: mechanisms of voltage- and state-dependence probed with site-directed mutant channels. J. Cardiovasc. Pharmacol. 2006, 47:21-29.
96. Huang X., et al. The effects of a novel anti-arrhythmic drug, acehytisine hydrochloride, on the human ether-a-go-go related gene K channel and its trafficking. Basic Clin. Pharmacol. Toxicol. 2009, 104:145-154.
97. Scholz E.P., et al. Inhibition of cardiac HERG channels by grapefruit flavonoid naringenin: implications for the influence of dietary compounds on cardiac repolarisation. Naunyn Schmiedebergs Arch. Pharmacol. 2005, 371:516-525.
98. Kim Y.J., et al. Papaverine, a vasodilator, blocks the pore of the HERG channel at submicromolar concentration. J. Cardiovasc. Pharmacol. 2008, 52:485-493.
99. Wang H.Z., et al. Inactivation gating determines nicotine blockade of human HERG channels. Am. J. Physiol. 1999, 277:H1081-H1088.
100. Bellocq C., et al. A common antitussive drug, clobutinol, precipitates the long QT syndrome 2. Mol. Pharmacol. 2004, 66:1093-1102.
101. Anchersen K., et al. Opioid maintenance patients with QTc prolongation: congenital long QT syndrome mutation may be a contributing risk factor. Drug Alcohol Depend. 2010, 112:216-219.
102. Hayashi K., et al. Probucol aggravates long QT syndrome associated with a novel missense mutation M124T in the N-terminus of HERG. Clin. Sci. (Lond.) 2004, 107:175-182.
103. Tu D.N., et al. Blockade of the human ether-a-go-go-related gene potassium channel by ketanserin. Sheng Li Xue Bao 2008, 60:525-534.
104. + channel. J. Mol. Cell. Cardiol. 2004, 36:701-705.
105. + channels by halofantrine. Naunyn Schmiedebergs Arch. Pharmacol. 2004, 370:484-491.
106. Scholz E.P., et al. Anticholinergic antiparkinson drug orphenadrine inhibits HERG channels: block attenuation by mutations of the pore residues Y652 or F656. Naunyn Schmiedebergs Arch. Pharmacol. 2007, 376:275-284.
107. Scholz E.P., et al. Drug binding to aromatic residues in the HERG channel pore cavity as possible explanation for acquired Long QT syndrome by antiparkinsonian drug budipine. Naunyn Schmiedebergs Arch. Pharmacol. 2003, 368:404-414.
108. Thomas D., et al. Inhibition of cardiac HERG currents by the DNA topoisomerase II inhibitor amsacrine: mode of action. Br. J. Pharmacol. 2004, 142:485-494.
109. Koo S.H., et al. Genetic polymorphisms in KCNQ1, HERG, KCNE1 and KCNE2 genes in the Chinese, Malay and Indian populations of Singapore. Br. J. Clin. Pharmacol. 2006, 61:301-308.
110. Anson B.D., et al. Molecular and functional characterization of common polymorphisms in HERG (KCNH2) potassium channels. Am. J. Physiol. Heart Circ. Physiol. 2004, 286:H2434-H2441.