2-[2-(3,4-Dichloro-phenyl)-2,3-dihydro-1H-isoindol-5-ylamino]-nicotinic acid (PD-307243) causes instantaneous current through human ether-a-go-go- related gene potassium channels

Molecular Pharmacology

Volumn 73, Issue 3, 2008, Pages 639-651

  Gordon, Earl ^a   Lozinskaya, Irina M ^a   Lin, Zuojun ^a   Semus, Simon F ^a   Blaney, Frank E ^b   Willette, Robert N ^a   Xu, Xiaoping ^a  

^a GLAXOSMITHKLINE   (United States)

^b GLAXOSMITHKLINE   (United Kingdom)

Author keywords

[No Author keywords available]

Indexed keywords

2 [2 (3,4 DICHLOROPHENYL) 2,3 DIHYDRO 1H ISOINDOL 5 YLAMINO]NICOTINIC ACID; NICOTINIC ACID DERIVATIVE; PD 307243; POTASSIUM CHANNEL HERG; POTASSIUM ION; UNCLASSIFIED DRUG;

ANIMAL CELL; ANIMAL TISSUE; ARTICLE; CHO CELL; CONCENTRATION RESPONSE; CONTROLLED STUDY; DRUG ACTIVITY; DRUG MECHANISM; ELECTRIC CURRENT; ELECTRIC POTENTIAL; EMBRYO; EXTRACELLULAR MATRIX; FEMALE; FILTER; GENETIC TRANSFECTION; HEART MUSCLE CELL; HEART MUSCLE POTENTIAL; HEART VENTRICLE WALL; HUMAN; HUMAN CELL; MALE; MEMBRANE POTENTIAL; NONHUMAN; PATCH CLAMP; POTASSIUM CURRENT; PRIORITY JOURNAL; PROTEIN EXPRESSION; RABBIT; VOLTAGE CLAMP; WHOLE CELL;

ACTION POTENTIALS; ANIMALS; BINDING SITES; CHO CELLS; CRICETINAE; CRICETULUS; DATA INTERPRETATION, STATISTICAL; DOSE-RESPONSE RELATIONSHIP, DRUG; ELECTRIC CONDUCTIVITY; ETHER-A-GO-GO POTASSIUM CHANNELS; HEART VENTRICLES; HUMANS; HYDROPHOBICITY; ISOINDOLES; KINETICS; MALE; MICE; MICROELECTRODES; MODELS, MOLECULAR; MOLECULAR STRUCTURE; MYOCYTES, CARDIAC; NIACIN; NICOTINIC ACIDS; PATCH-CLAMP TECHNIQUES; PROTEIN BINDING; PROTEIN STRUCTURE, SECONDARY; PROTEIN STRUCTURE, TERTIARY; RABBITS; TRANSFECTION;

EID: 40849140985     PISSN: 0026895X     EISSN: 15210111     Source Type: Journal    
DOI: 10.1124/mol.107.041152     Document Type: Article

References (33)

1. Abbott GW, Sesti F, Splawski I, Buck ME, Lehmann MH, Timothy KW, Keating MT, and Goldstein SA (1999) MiRP1 forms IKr potassium channels with HERG and is associated with cardiac arrhythmia. Cell 97:175-187.
2. Brown AM (2005) HERG block, QT liability and sudden cardiac death. Novartis Found Symp 266:118-131.
3. Brugada R, Hong K, Dumaine R, Cordeiro J, Gaita F, Borggrefe M, Menendez TM, Brugada J, Pollevick GD, Wolpert C, et al. (2004) Sudden death associated with short-QT syndrome linked to mutations in HERG. Circulation 109:30-35.
4. Casis O, Olesen SP, and Sanguinetti MC (2006) Mechanism of action of a novel human ether-a-go-go-related gene channel activator. Mol Pharmacol 69:658-665.
5. Cordeiro JM, Brugada R, Wu YS, Hong K, and Dumaine R (2005) Modulation of IKr inactivation by mutation N588K in KCNH2: a link to arrhythmogenesis in short QT syndrome. Cardiovasc Res 67:498-509.
6. Hansen RS, Diness TG, Christ T, Demnitz J, Ravens U, Olesen SP, and Grunnet M (2006a) Activation of human ether-a-go-go-related gene potassium channels by the diphenylurea 1,3-bis-(2-hydroxy-5-trifluoromethyl-phenyl)-urea (NS1643). Mol Pharmacol 69:266-277.
7. Hansen RS, Diness TG, Christ T, Wettwer E, Ravens U, Olesen SP, and Grunnet M (2006b) Biophysical characterization of the new human ether-a-go-go-related gene channel opener NS3623 [N-(4-bromo-2-(1 H-tetrazol-5-Yl)-phenyl)-N′-(3′-trifluoromethylphenyl) urea]. Mol Pharmacol 70:1319-1329.
8. Jiang M, Zhang M, Maslennikov IV, Liu J, Wu DM, Korolkova YV, Arseniev AS, Grishin EV, and Tseng GN (2005) Dynamic conformational changes of extracellular S5-P linkers in the HERG channel. J Physiol 569:75-89.
9. + current by dofetilide. Circ Res 72:75-83.
10. + channel. Mol Pharmacol 67:827-836.
11. Kiehn J, Lacerda AE, and Brown AM (1999) Pathways of HERG inactivation. Am J Physiol 277:H199-H210.
12. Lalik PH, Krafte DS, Volberg WA, and Ciccarelli RB (1993) Characterization of endogenous sodium channel gene expressed in Chinese hamster ovary cells. Am J Physiol 264:C803-C809.
13. Liu J, Zhang M, Jiang M, and Tseng GN (2002) Structural and functional role of the extracellular S5-p linker in the HERG potassium channel. J Gen Physiol 120:723-737.
14. + channel. Science 309:897-903.
15. + channel mutation in the 'short QT syndrome': mechanism of gain-infunction determined at 37 degrees C. Biochem Biophys Res Commun 334:441-449.
16. 3 receptor antagonists. J Med Chem 50:5076-5089.
17. Modell SM and Lehmann MH (2006) The long QT syndrome family of cardiac ion channelopathies: a HuGE review. Genet Med 8:143-155.
18. Rials SJ, Wu Y, Xu X, Filart RA, Marinchak RA, and Kowey PR (1997) Regression of left ventricular hypertrophy with captopril restores normal ventricular action potential duration, dispersion of refractoriness, and vulnerability to inducible ventricular fibrillation. Circulation 96:1330-1336.
19. Ks potassium channel. Nature 384:80-83.
20. Seebohm G (2005) Activators of cation channels: potential in treatment of channelopathies. Mol Pharmacol 67:585-588.
21. Smith PL, Baukrowitz T, and Yellen G (1996) The inward rectification mechanism of the HERG cardiac potassium channel. Nature 379:833-836.
22. Spector PS, Curran ME, Zou A, Keating MT, and Sanguinetti MC (1996) Fast inactivation causes rectification of the IKr channel. J Gen Physiol 107:611-619.
23. + channel S5P extracellular linker: role of an amphipathic α-helix in C-type inactivation. J Biol Chem 278:42136-42148.
24. Tseng GN, Sonawane KD, Korolkova YV, Zhang M, Liu J, Grishin EV, and Guy HR (2007) Probing the outer mouth structure of the HERG channel with peptide toxin footprinting and molecular modeling. Biophys J 92:3524-3540.
25. + channel: progress in understanding the molecular basis of its unusual gating kinetics. Eur Biophys J 33:89-97.
26. Wible BA, Hawryluk P, Ficker E, Kuryshev YA, Kirsch G, and Brown AM (2005) HERG-lite: a novel comprehensive high-throughput screen for drug-induced HERG risk. J Pharmacol Toxicol Methods 52:136-145.
27. Witchel HJ (2007) The HERG potassium channel as a therapeutic target. Expert Opin Ther Targets 11:321-336.
28. Yu SP and Kerchner GA (1998) Endogenous voltage-gated potassium channels in human embryonic kidney (HEK293) cells. J Neurosci Res 52:612-617.
29. Zeng H, Lozinskaya IM, Lin Z, Willette RN, Brooks DP, and Xu X (2006) Mallotoxin is a novel human ether-a-go-go-related gene (HERG) potassium channel activator. J Pharmacol Exp Ther 319:957-962.
30. Zeng H, Weiger TM, Fei H, Jaramillo AM, and Levitan IB (2005) The amino terminus of slob, slowpoke channel binding protein, critically influences its modulation of the channel. J Gen Physiol 125:631-640.
31. Zhou J, Augelli-Szafran CE, Bradley JA, Chen X, Koci BJ, Volberg WA, Sun Z, and Cordes JS (2005) Novel potent human ether-a-go-go-related gene (HERG) potassium channel enhancers and their in vitro antiarrhythmic activity. Mol Pharmacol 68:876-884.
32. Zhou Z, Gong Q, Ye B, Fan Z, Makielski JC, Robertson GA, and January CT (1998) Properties of HERG Channels Stably Expressed in HEK 293 cells studied at physiological temperature. Biophys J 74:230-241.
33. + channels expressed in Xenopus oocytes reduces rectification by shifting the voltage dependence of inactivation. J Physiol 509:129-137.