333
Views
37
CrossRef citations to date
0
Altmetric
Review

Molecular mechanisms for drug interactions with hERG that cause long QT syndrome

, &
Pages 81-94 | Published online: 01 Feb 2006

Bibliography

  • ROY M, DUMAINE R, BROWN AM: HERG, a primary human ventricular target of the nonsedating antihistamine terfenadine. Circulation (1996) 94(4):817-823.
  • RAMPE D, ROY ML, DENNIS A, BROWN AM: A mechanism for the proarrhythmic effects of cisapride (Propulsid): high affinity blockade of the human cardiac potassium channel HERG. FEBS Lett. (1997) 417(1):28-32.
  • DOYLE DA, MORAIS CABRAL J, PFUETZNER RA etal.: The structure of the potassium channel: molecular basis of K+ conduction and selectivity. Science (1998) 280(5360):69-77.
  • ZHOU Y, MORAIS-CABRAL JH, KAUFMAN A, MACKINNON R: Chemistry of ion coordination and hydration revealed by a K+ channel-Fab complex at 2.0 A resolution. Nature (2001) 414(6859):43-48.
  • JIANG Y, LEE A, CHEN J etal.: The open pore conformation of potassium channels. Nature (2002) 417(6888):523-526.
  • MORAIS CABRAL JH, LEE A, COHENSL etal.: Crystal structure and functional analysis of the HERG potassium channel N terminus: a eukaryotic PAS domain. Cell (1998) 95(5):649-655.
  • ZAGOTTA WN, OLIVIER NB, BLACKKD etal.: Structural basis for modulation and agonist specificity of HCN pacemaker channels. Nature (2003) 425(6954):200-205.
  • CLAYTON GM, SILVERMAN WR, HEGINBOTHAM L, MORAIS-CABRALJH: Structural basis of ligand activation in a cyclic nucleotide regulated potassium channel. Cell (2004) 119(5):615-627.
  • LIU J, ZHANG M, JIANG M, TSENGGN: Structural and functional role of the extracellular s5-p linker in the HERG potassium channel. J. Gen. Physiol. (2002) 120(5):723-737.
  • TORRES AM, BANSAL PS, SUNDE M etal.: Structure of the HERG K+ channel S5P extracellular linker: role of an amphipathic alpha-helix in C-type inactivation. J. Biol. Chem. (2003) 278(43):42136-42148.
  • PARDO-LOPEZ L, ZHANG M, LIU J etal.: Mapping the binding site of a human ether-a-go-go-related gene-specific peptide toxin (ErgTx) to the channels outer vestibule. J. Biol. Chem. (2002) 277(19):16403-16411.
  • MORAIS-CABRAL JH, ZHOU Y, MACKINNON R: Energetic optimization of ion conduction rate by the K+ selectivity filter. Nature (2001) 414(6859):37-42.
  • BERNECHE S, ROUX B: Energetics of ion conduction through the K+ channel. Nature (2001) 414(6859):73-77.
  • SHRIVASTAVA IH, TIELEMAN DP, BIGGIN PC, SANSOM MS: K(+) versus Na(+) ions in a K channel selectivity filter: a simulation study. Biophys. J. (2002) 83(2):633-645.
  • ZHOU Y, MACKINNON R: Ion binding affinity in the cavity of the KcsA potassium channel. Biochemistry (2004) 43(17):4978-4982.
  • JIANG Y, LEE A, CHEN J etal.: X-ray structure of a voltage-dependent K+ channel. Nature (2003) 423(6935):33-41.
  • YANG T, RODEN DM: Extracellular potassium modulation of drug block of IKr. Implications for torsade de pointes and reverse use-dependence. Circulation (1996) 93(3):407-411.
  • WANG S, MORALES MJ, LIU S, STRAUSS HC, RASMUSSON RL: Modulation of HERG affinity for E-4031 by [K+]o and C-type inactivation. FEBS Lett. (1997) 417(1):43-47.
  • MITCHESON JS, CHEN J, LIN M, CULBERSON C, SANGUINETTI MC: A structural basis for drug-induced long QT syndrome. Proc. Natl. Acad. Sci.USA (2000) 97(22):12329-12333.
  • MITCHESON JS, CHEN J, SANGUINETTI MC: Trapping of a methanesulfonanilide by closure of the HERG potassium channel activation gate. J. Gen. Physiol. (2000) 115(3):229-240.
  • LONG SB, CAMPBELL EB, MACKINNON R: Crystal structure of a mammalian voltage-dependent Shaker family K+ channel. Science (2005) 309(5736):897-903.
  • DEL CAMINO D, HOLMGREN M, LIUY, YELLEN G: Blocker protection in the pore of a voltage-gated K+ channel and its structural implications. Nature (2000) 403(6767):321-325.
  • KAMIYA K, MITCHESON JS, YASUI K, KODAMA I, SANGUINETTI MC: Open channel block of HERG K(+) channels by vesnarinone. Mol. Pharmacol. (2001) 60(2):244-253.
  • LEES-MILLER JP, DUAN Y, TENG GQ, DUFF HJ: Molecular determinant of high-affinity dofetilide binding to HERG1 expressed in Xenopus oocytes: involvement of S6 sites. Mol. Pharmacol. (2000) 57(2):367-374.
  • PERRY M, DE GROOT MJ, HELLIWELL R etal.: Structural determinants of HERG channel block by clofilium and ibutilide. Mol. Pharmacol. (2004) 66(2):240-249.
  • FERNANDEZ D, GHANTA A, KAUFFMAN GW, SANGUINETTI MC: Physicochemical features of the HERG channel drug binding site. J. Biol. Chem. (2004) 279(11):10120-10127.
  • SANCHEZ-CHAPULA JA, NAVARRO-POLANCO RA, CULBERSON C, CHEN J, SANGUINETTI MC: Molecular determinants of voltage-dependent human ether-a-go-go related gene (HERG) K+ channel block. J. Biol. Chem. (2002) 277(26):23587-23595.
  • SANCHEZ-CHAPULA JA, FERRER T, NAVARRO-POLANCO RA, SANGUINETTI MC: 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. (2003) 63(5):1051-1058.
  • WITCHEL HJ, DEMPSEY CE, SESSIONS RB etal.: The low-potency, voltage-dependent HERG blocker propafenone-molecular determinants and drug trapping. Mol. Pharmacol. (2004) 66(5):1201-1212.
  • MITCHESON JS, PERRY MD: Molecular determinants of high-affinity drug binding to HERG channels. Curr. Opin. Drug Discov. Devel. (2003) 6(5):667-674.
  • MILNES JT, CROCIANI O, ARCANGELI A, HANCOX JC, WITCHEL HJ: Blockade of HERG potassium currents by fluvoxamine: incomplete attenuation by S6 mutations at F656 or Y652. Br. J. Pharmacol. (2003) 139(5):887-898.
  • MITCHESON JS: Drug binding to HERG channels: evidence for a non-aromatic binding site for fluvoxamine. Br. J. Pharmacol. (2003) 139(5):883-884.
  • SHEALY RT, MURPHY AD, RAMARATHNAM R, JAKOBSSON E, SUBRAMANIAM S: Sequence-function analysis of the K+-selective family of ion channels using a comprehensive alignment and the KcsA channel structure. Biophys. J. (2003) 84(5):2929-2942.
  • KUO A, GULBIS JM, ANTCLIFF JF etal.: Crystal structure of the potassium channel KirBac1.1 in the closed state. Science (2003) 300(5627):1922-1926.
  • ZHOU M, MACKINNON R: A mutant KcsA K(+) channel with altered conduction properties and selectivity filter ion distribution. J. Mol. Biol. (2004) 338(4):839-846.
  • PERRY M, STANSFELD PJ, LEANEY J etal.: Drug binding interactions in the inner cavity of hERG: Molecular insights from structure-activity relationships of clofilium and ibutilide analogues. Mol. Pharmacol. (2005) (In Press).
  • FICKER E, JAROLIMEK W, KIEHN J, BAUMANN A, BROWN AM: Molecular determinants of dofetilide block of HERG K+ channels. Circ. Res. (1998) 82(3):386-395.
  • SMITH PL, BAUKROWITZ T, YELLENG: The inward rectification mechanism of the HERG cardiac potassium channel. Nature (1996) 379(6568):833-836.
  • TSENG GN, GUY HR: Structurefunction studies of the outer mouth and voltage sensor domain of hERG. Novartis Found. Symp. (2005) 266:19-35; discussion 35-45.
  • HERZBERG IM, TRUDEAU MC, ROBERTSON GA: Transfer of rapid inactivation and sensitivity to the class III antiarrhythmic drug E-4031 from HERG to M-eag channels. J. Physiol. (1998) 511(Pt1):3-14.
  • FICKER E, JAROLIMEK W, BROWNAM: Molecular determinants of inactivation and dofetilide block in ether a-go-go (EAG) channels and EAG-related K(+) channels. Mol. Pharmacol. (2001) 60(6):1343-1348.
  • CHEN J, SEEBOHM G, SANGUINETTIMC: Position of aromatic residues in the S6 domain, not inactivation, dictates cisapride sensitivity of HERG and eag potassium channels. Proc. Natl. Acad. Sci.USA (2002) 99(19):12461-12466.
  • HEGINBOTHAM L, MACKINNON R: The aromatic binding site for tetraethylammonium ion on potassium channels. Neuron (1992) 8(3):483-491.
  • KOROLKOVA YV, TSENG GN, GRISHIN EV: Unique interaction of scorpion toxins with the hERG channel. J. Mol. Recognit. (2004) 17(3):209-217.
  • VOLBERG WA, KOCI BJ, SU W, LIN J, ZHOU J: Blockade of human cardiac potassium channel human ether-a-go-go-related gene (HERG) by macrolide antibiotics. J. Pharmacol. Exp. Ther. (2002) 302(1):320-327.
  • AKIMOTO K, FURUTANI M, IMAMURA S etal.: Novel missense mutation (G601S) of HERG in a Japanese long QT syndrome family. Hum. Mutat. (1998) (Suppl. 1):S184-S186.
  • FURUTANI M, TRUDEAU MC, HAGIWARA N etal.: Novel mechanism associated with an inherited cardiac arrhythmia: defective protein trafficking by the mutant HERG (G601S) potassium channel. Circulation (1999) 99(17):2290-2294.
  • DELISLE BP, ANSON BD, RAJAMANI S, JANUARY CT: Biology of cardiac arrhythmias: ion channel protein trafficking. Circ. Res. (2004) 94(11):1418-1428.
  • ZHOU Z, GONG Q, JANUARY CT: Correction of defective protein trafficking of a mutant HERG potassium channel in human long QT syndrome. Pharmacological and temperature effects. J. Biol. Chem. (1999) 274(44):31123-31126.
  • FICKER E, OBEJERO-PAZ CA, ZHAO S, BROWN AM: The binding site for channel blockers that rescue misprocessed human long QT syndrome type 2 ether-a-go-go-related gene (HERG) mutations. J. Biol. Chem. (2002) 277(7):4989-4998.
  • FICKER E, DENNIS A, KURYSHEV Y, WIBLE BA, BROWN AM: HERG channel trafficking. Novartis Found. Symp. (2005) 266:57-69; discussion 70-54, 95-59.
  • FICKER E, KURYSHEV YA, DENNIS AT etal.: Mechanisms of arsenic-induced prolongation of cardiac repolarization. Mol. Pharmacol. (2004) 66(1):33-44.
  • KURYSHEV YA, FICKER E, WANG L etal.: Pentamidine-induced long QT syndrome and block of hERG trafficking. J. Pharmacol. Exp. Ther. (2005) 312(1):316-323.
  • ECKHARDT LL, RAJAMANI S, JANUARY CT: Protein trafficking abnormalities: a new mechanism in drug-induced long QT syndrome. Br. J. Pharmacol. (2005) 145(1):3-4.
  • CORDES JS, SUN Z, LLOYD DB etal.: Pentamidine reduces hERG expression to prolong the QT interval. Br. J. Pharmacol. (2005) 145(1):15-23.
  • BROWN AM: HERG block, QT liability and sudden cardiac death. Novartis Found. Symp. (2005) 266:118-131; discussion 131-115, 155-118.
  • WITCHEL HJ, MILNES JT, MITCHESON JS, HANCOX JC: Troubleshooting problems with invitro screening of drugs for QT interval prolongation using HERG K+ channels expressed in mammalian cell lines and Xenopus oocytes. J. Pharmacol. Toxicol. Methods (2002) 48(2):65-80.
  • CHIU PJ, MARCOE KF, BOUNDS SE etal.: Validation of a [3H]astemizole binding assay in HEK293 cells expressing HERG K+ channels. J. Pharmacol. Sci. (2004) 95(3):311-319.
  • CHENG CS, ALDERMAN D, KWASH J etal.: A high-throughput HERG potassium channel function assay: an old assay with a new look. Drug Dev. Ind. Pharm. (2002) 28(2):177-191.
  • WIBLE BA, HAWRYLUK P, FICKER E etal.: HERG-Lite(R): a novel comprehensive high-throughput screen for drug-induced hERG risk. J. Pharmacol. Toxicol. Methods (2005) 52(1):136-145.
  • SANGUINETTI MC, MITCHESON JS: Predicting drug-hERG channel interactions that cause acquired long QT syndrome. Trends Pharmacol. Sci. (2005) 26(3):119-124.
  • RECANATINI M, POLUZZI E, MASETTI M, CAVALLI A, DE PONTI F: QT prolongation through hERG K(+) channel blockade: current knowledge and strategies for the early prediction during drug development. Med. Res. Rev. (2005) 25(2):133-166.
  • PEARLSTEIN RA, VAZ RJ, KANG J etal.: Characterization of HERG potassium channel inhibition using CoMSiA 3D QSAR and homology modeling approaches. Bioorg. Med. Chem. Lett. (2003) 13(10):1829-1835.
  • CAVALLI A, POLUZZI E, DE PONTI F, RECANATINI M: Toward a pharmacophore for drugs inducing the long QT syndrome: insights from a CoMFA study of HERG K(+) channel blockers. J. Med. Chem. (2002) 45(18):3844-3853.
  • EKINS S, CRUMB WJ, SARAZAN RD, WIKEL JH, WRIGHTON SA: Three-dimensional quantitative structureactivity relationship for inhibition of human ether-a-go-go-related gene potassium channel. J. Pharmacol. Exp. Ther. (2002) 301(2):427-434.
  • ARONOV AM, GOLDMAN BB: A model for identifying HERG K+ channel blockers. Bioorg. Med. Chem. (2004) 12(9):2307-2315.
  • OSTERBERG F, AQVIST J: Exploring blocker binding to a homology model of the open hERG K+ channel using docking and molecular dynamics methods. FEBS Lett. (2005) 579(13):2939-2944.
  • HANSSON T, MARELIUS J, AQVIST J: Ligand binding affinity prediction by linear interaction energy methods. J. Comput. Aided Mol. Des. (1998) 12(1):27-35.
  • CRUMB WJ, JR.: Loratadine blockade of K(+) channels in human heart: comparison with terfenadine under physiological conditions. J. Pharmacol. Exp. Ther. (2000) 292(1):261-264.
  • TAGLIALATELA M, CASTALDO P, PANNACCIONE A etal.: Cardiac ion channels and antihistamines: possible mechanisms of cardiotoxicity. Clin. Exp. Allergy (1999) 29(Suppl. 3):182-189.
  • RAJAMANI S, ANDERSON CL, ANSONBD, JANUARY CT: Pharmacological rescue of human K(+) channel long-QT2 mutations: human ether-a-go-go-related gene rescue without block. Circulation (2002) 105(24):2830-2835.
  • TAGLIALATELA M, PANNACCIONE A, CASTALDO P etal.: Molecular basis for the lack of HERG K+ channel block-related cardiotoxicity by the H1 receptor blocker cetirizine compared with other second-generation antihistamines. Mol. Pharmacol. (1998) 54(1):113-121.
  • KIRSCH GE, TREPAKOVA ES, BRIMECOMBE JC etal.: Variability in the measurement of hERG potassium channel inhibition: effects of temperature and stimulus pattern. J. Pharmacol. Toxicol. Methods (2004) 50(2):93-101.
  • LINDQUIST M, EDWARDS IR: Risks of non-sedating antihistamines. Lancet (1997) 349(9061):1322.
  • REDFERN WS, CARLSSON L, DAVISAS etal.: Relationships between preclinical cardiac electrophysiology, clinical QT interval prolongation and torsade de pointes for a broad range of drugs: evidence for a provisional safety margin in drug development. Cardiovasc. Res. (2003) 58(1):32-45.
  • RODEN DM: Taking the idio out of idiosyncratic: predicting torsades de pointes. Pacing Clin. Electrophysiol. (1998) 21(5):1029-1034.
  • RODEN DM, YANG T: Protecting the heart against arrhythmias: potassium current physiology and repolarization reserve. Circulation (2005) 112(10):1376-1378.
  • RAJAMANI R, TOUNGE BA, LI J, REYNOLDS CH: A two-state homology model of the hERG K+ channel: application to ligand binding. Bioorg. Med. Chem. Lett. (2005) 15(6):1737-1741.
  • LONG SB, CAMPBELL EB, MACKINNON R: Voltage sensor of Kv1.2: structural basis of electromechanical coupling. Science (2005) 309(5736):903-908.
  • JIANG Y, RUTA V, CHEN J, LEE A, MACKINNON R: The principle of gating charge movement in a voltage-dependent K+ channel. Nature (2003) 423(6935):42-48.
  • JOHNSON JP, JR., ZAGOTTA WN: The carboxyl-terminal region of cyclic nucleotide-modulated channels is a gating ring, not a permeation path. Proc. Natl. Acad. Sci. USA (2005) 102(8):2742-2747.
  • DUMAINE R, ROY ML, BROWN AM: Blockade of HERG and Kv1.5 by ketoconazole. J. Pharmacol. Exp. Ther. (1998) 286(2):727-735.
  • AMENT PW, PATERSON A: Drug interactions with the nonsedating antihistamines. Am. Fam. Physician (1997) 56(1):223-231.
  • RIDLEY JM, MILNES JT, WITCHEL HJ, HANCOX JC: High affinity HERG K(+) channel blockade by the antiarrhythmic agent dronedarone: resistance to mutations of the S6 residues Y652 and F656. Biochem. Biophys. Res. Commun. (2004) 325(3):883-891.

Reprints and Corporate Permissions

Please note: Selecting permissions does not provide access to the full text of the article, please see our help page How do I view content?

To request a reprint or corporate permissions for this article, please click on the relevant link below:

Academic Permissions

Please note: Selecting permissions does not provide access to the full text of the article, please see our help page How do I view content?

Obtain permissions instantly via Rightslink by clicking on the button below:

If you are unable to obtain permissions via Rightslink, please complete and submit this Permissions form. For more information, please visit our Permissions help page.