Ranolazine inhibition of hERG potassium channels: Drug-pore interactions and reduced potency against inactivation mutants

Journal of Molecular and Cellular Cardiology

Volumn 74, Issue , 2014, Pages 220-230

  Du, Chunyun ^a   Zhang, Yihong ^a   El Harchi, Aziza ^a   Dempsey, Christopher E ^a   Hancox, Jules C ^a  

^a UNIVERSITY OF BRISTOL   (United Kingdom)

Author keywords

Antiarrhythmic; Docking; HERG; Lidocaine; QT interval; Ranolazine

Indexed keywords

LIDOCAINE; POTASSIUM CHANNEL HERG; RANOLAZINE; ACETANILIDE DERIVATIVE; ANTIARRHYTHMIC AGENT; ERG1 POTASSIUM CHANNEL; PIPERAZINE DERIVATIVE; POTASSIUM;

ARTICLE; CONTROLLED STUDY; DRUG INTERACTION; DRUG MECHANISM; DRUG POTENCY; DRUG SENSITIVITY; ELECTROPHYSIOLOGY; GENETIC TRANSFECTION; HEK293 CELL LINE; IC 50; MOLECULAR DOCKING; MUTANT; MUTATION; PHARMACOLOGICAL BLOCKING; POTASSIUM TRANSPORT; PRIORITY JOURNAL; VOLTAGE CLAMP TECHNIQUE; WILD TYPE; ACTION POTENTIAL; CHEMISTRY; DOSE RESPONSE; DRUG EFFECTS; GENE EXPRESSION; GENETICS; HUMAN; ION TRANSPORT; METABOLISM; PATCH CLAMP TECHNIQUE; PROTEIN SECONDARY STRUCTURE; PROTEIN TERTIARY STRUCTURE; STRUCTURE ACTIVITY RELATION; TRANSGENE;

ACETANILIDES; ACTION POTENTIALS; ANTI-ARRHYTHMIA AGENTS; DOSE-RESPONSE RELATIONSHIP, DRUG; ETHER-A-GO-GO POTASSIUM CHANNELS; GENE EXPRESSION; HEK293 CELLS; HUMANS; ION TRANSPORT; LIDOCAINE; MOLECULAR DOCKING SIMULATION; MUTATION; PATCH-CLAMP TECHNIQUES; PIPERAZINES; POTASSIUM; PROTEIN STRUCTURE, SECONDARY; PROTEIN STRUCTURE, TERTIARY; STRUCTURE-ACTIVITY RELATIONSHIP; TRANSGENES;

EID: 84904763623     PISSN: 00222828     EISSN: 10958584     Source Type: Journal    
DOI: 10.1016/j.yjmcc.2014.05.013     Document Type: Article

References (70)

1. Nattel S. Class III drugs: amiodarone, bretylium, ibutilide and sotalol. Cardiac electrophysiology; from cell to bedside 1999, 921-932. 3rd ed. D.P. Zipes, J. Jalife (Eds.).
2. Hondeghem L.M., Snyders D.J. Class III antiarrhythmic agents have a lot of potential but a long way to go. Circulation 1990, 81:686-690.
3. Sanguinetti M.C., Tristani-Firouzi M. hERG potassium channels and cardiac arrhythmia. Nature March 23 2006, 440:463-469.
4. Hancox J.C., McPate M.J., El Harchi A., Zhang Y.H. The hERG potassium channel and hERG screening for drug-induced torsades de pointes. Pharmacol Ther 2008, 119:118-132.
5. Lees-Miller J.P., Duan Y., Teng G.Q., Duff H.J. Molecular determinant of high affinity dofetilide binding to HERG1 expressed in Xenopus oocytes: involvement of S6 sites. Mol Pharmacol 2000, 57:367-374.
6. Paul A.A., Witchel H.J., Hancox J.C. Inhibition of HERG potassium channel current by the Class 1a antiarrhythmic agent disopyramide. Biochem Biophys Res Commun 2001, 280:1243-1250.
7. Arias C., Gonzalez T., Moreno I., Caballero R., Delpon E., Tamargo J., et al. Effects of propafenone and its main metabolite, 5-hydroxypropafenone, on HERG channels. Cardiovasc Res 2003, 57(3):660-669.
8. + channel mutation: differential impact on selected class I and class III antiarrhythmic drugs. Br J Pharmacol 2008, 155:957-966.
9. Wang D.W., Kiyosue T., Sato T., Arita M. Comparison of the effects of Class-I antiarrhythmic drugs, cibenzoline, mexiletine and flecainide, on the delayed rectifier K current of guinea-pig ventricular myocytes. J Mol Cell Cardiol 1996, 28:893-903.
10. Mitcheson J.S., Hancox J.C. Modulation by mexiletine of action potentials, L-type Ca current and delayed rectifier K current recorded from isolated rabbit atrioventricular nodal myocytes. Pflugers Arch 1997, 434:855-858.
11. Paul A.A., Witchel H.J., Hancox J.C. Inhibition of heterologously expressed HERG potassium channels by flecainide and comparison with quinidine, propafenone and lignocaine. Br J Pharmacol 2002, 136:717-729.
12. Viskin S. Long QT, syndromes and torsade de pointes. Lancet 1999, 354:1625-1633.
13. Yap Y.G., Camm A.J. Drug induced QT prolongation and torsades de pointes. Heart 2003, 89:1363-1372.
14. Hancox J.C., Doggrell S.A. Perspective: does ranolazine have potential for the treatment of atrial fibrillation?. Expert Opin Investig Drugs 2010, 19:1465-1474.
15. Saklani P., Skanes A. Novel anti-arrhythmic medications in the treatment of atrial fibrillation. Curr Cardiol Rev 2012, 8:302-309.
16. Singh B.N., Wadhani N. Antiarrhythmic and proarrhythmic properties of QT-prolonging antianginal drugs. J Cardiovasc Pharmacol Ther 2004, 9:S85-S97.
17. Zaza A., Belardinelli L., Shryock J.C. Pathophysiology and pharmacology of the cardiac "late sodium current.". Pharmacol Ther 2008, 119:326-339.
18. Chaitman B.R. Efficacy and safety of a metabolic modulator drug in chronic stable angina: review of evidence from clinical trials. J Cardiovasc Pharmacol Ther 2004, 9:S47-S64.
19. Scirica B.M., Morrow D.A., Hod H., Murphy S.A., Belardinelli L., Hedgepath C.M., et al. Effect of ranolazine, an antianginal agent with novel electrophysiological properties, on the incidence of arrhythmias in patients with non ST-segment elevation acute coronary syndrome: results from the Metabolic Efficiency With Ranolazine for Less Ischemia in Non ST-Elevation Acute Coronary Syndrome Thrombolysis in Myocardial Infarction 36 (MERLIN-TIMI 36) randomized controlled trial. Circulation 2007, 116:1647-1652.
20. Murdock D.K., Kersten M., Kaliebe J., Larrain G. The use of oral ranolazine to convert new or paroxysmal atrial fibrillation: a review of experience with implications for possible "pill in the pocket" approach to atrial fibrillation. Indian Pacing Electrophysiol J 2009, 9:260-267.
21. Murdock D.K., Kaliebe J., Larrain G. The use of ranolazine to facilitate electrical cardioversion in cardioversion-resistant patients: a case series. Pacing Clin Electrophysiol 2012, 35:302-307.
22. + current by ranolazine. Heart Rhythm 2009, 6:1625-1631.
23. + current in the heart. Am J Physiol Heart Circ Physiol 2009, 297:H1048-H1057.
24. Burashnikov A., Di Diego J.M., Zygmunt A.C., Belardinelli L., Antzelevitch C. Atrium-selective sodium channel block as a strategy for suppression of atrial fibrillation: differences in sodium channel inactivation between atria and ventricles and the role of ranolazine. Circulation 2007, 116:1449-1457.
25. Antzelevitch C., Belardinelli L., Wu L., Fraser H., Zygmunt A.C., Burashnikov A., et al. Electrophysiologic properties and antiarrhythmic actions of a novel antianginal agent. J Cardiovasc Pharmacol Ther 2004 September, 9(Suppl. 1):S65-S83.
26. + current. J Cardiovasc Pharmacol 2008, 51:581-589.
27. Trenor B., Gomis-Tena J., Cardona K., Romero L., Rajamani S., Belardinelli L., et al. In silico assessment of drug safety in human heart applied to late sodium current blockers. Channels (Austin) 2013, 7:249-262. [21].
28. Kumar K., Nearing B.D., Carvas M., Nascimento B.C., Acar M., Belardinelli L., et al. Ranolazine exerts potent effects on atrial electrical properties and abbreviates atrial fibrillation duration in the intact porcine heart. J Cardiovasc Electrophysiol 2009, 20:796-802.
29. Smith J.L., Reloj A.R., Nataraj P.S., Bartos D.C., Schroder E.A., Moss A.J., et al. Pharmacological correction of long QT-linked mutations in KCNH2 (hERG) increases the trafficking of Kv11.1 channels stored in the transitional endoplasmic reticulum. Am J Physiol Cell Physiol 2013, 305:C919-C930.
30. Perrin M.J., Kuchel P.W., Campbell T.J., Vandenberg J.I. Drug binding to the inactivated state is necessary but not sufficient for high-affinity binding to human ether-à-go-go-related gene channels. Mol Pharmacol 2008, 74:1443-1452.
31. Fredj S., Sampson K.J., Liu H., Kass R.S. Molecular basis of ranolazine block of LQT-3 mutant sodium channels: evidence for site of action. Br J Pharmacol 2006, 148:16-24.
32. Zhou Z., Gong Q., Ye B., Fan Z., Makielski J.C., Robertson G.A., et al. Properties of HERG channels stably expressed in HEK 293 cells studied at physiological temperature. Biophys J 1998, 74:230-241.
33. Milnes J.T., Crociani O., Arcangeli A., Hancox J.C., Witchel H.J. Blockade of HERG potassium currents by fluvoxamine: incomplete attenuation by S6 mutations at F656 or Y652. Br J Pharmacol 2003, 139:887-898.
34. El Harchi A., Zhang Y.H., Hussein L., Dempsey C.E., Hancox J.C. Molecular determinants of hERG potassium channel inhibition by disopyramide. J Mol Cell Cardiol 2012, 52:185-195.
35. + channel S4 domain L532P mutation: characterization at 37°C. Biochim Biophys Acta 1808, 2011:2477-2487.
36. Levi A.J., Hancox J.C., Howarth F.C., Croker J., Vinnicombe J. A method for making rapid changes of superfusate whilst maintaining temperature at 37°C. Pflugers Arch 1996, 432:930-937.
37. Jiang Y., Lee A., Chen J., Cadene M., Chait B.T., MacKinnon R. Crystal structure and mechanism of a calcium-gated potassium channel. Nature 2002, 417:515-522.
38. Witchel H.J., Dempsey C.E., Sessions R.B., Perry M., Milnes J.T., Hancox J.C., et al. The low-potency, voltage-dependent HERG channel blocker propafenone - molecular determinants and drug trapping. Mol Pharmacol 2004, 66:1201-1212.
39. Dempsey C.E., Wright D., Colenso C.K., Sessions R.B., Hancox J.C. Assessing HERG pore models as templates for drug docking using published experimental constraints: the inactivated state in the context of drug block. J Chem Inf Model 2014, 54:601-612.
40. Farid R., Day T., Friesner R.A., Pearlstein R.A. New insights about HERG blockade obtained from protein modeling, potential energy mapping, and docking studies. Bioorg Med Chem 2006, 14:3160-3173.
41. + channels involved in variant 1 short QT syndrome. J Mol Cell Cardiol 2006, 41:563-566.
42. Kr. Implications for torsade de pointes and reverse use-dependence. Circulation 1996, 93:407-411.
43. Barrows B., Cheung K., Bialobrzeski T., Foster J., Schulze J., Miller A. Extracellular potassium dependency of block of HERG by quinidine and cisapride is primarily determined by the permeant ion and not by inactivation. Channels (Austin) 2009, 3:239-248.
44. Ficker E., Jarolimek W., Kiehn J., Baumann A., Brown A.M. Molecular determinants of dofetilide block of HERG K channels. Circ Res 1998, 82:386-395.
45. Duncan R.S., McPate M.J., Ridley J.M., Gao Z., James A.F., Leishman D.J., et al. Inhibition of the HERG potassium channel by the tricyclic antidepressant doxepin. Biochem Pharmacol 2007, 74:425-437.
46. Kr inactivation by mutation N588K in KCNH2: a link to arrhythmogenesis in short QT syndrome. Cardiovas Res 2005, 67:498-509.
47. + channel mutation in the 'short QT syndrome': mechanism of gain-in-function determined at 37°C. Biochem Biophys Res Commun 2005, 334:441-449.
48. Wolpert C., Schimpf R., Giustetto C., Antzelevitch C., Cordeiro J., Dumaine R., 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.
49. Brugada R., Hong K., Dumaine R., Cordeiro J., Gaita F., Borgreffe M., et al. Sudden death associated with short-QT syndrome linked to mutations in HERG. Circulation 2004, 109:30-35.
50. Hong K., Bjeerregaard P., Gussak I., Brugada R. Short QT syndrome and atrial fibrillation caused by mutation in KCNH2. J Cardiovasc Electrophysiol 2005, 16:394-396.
51. Mitcheson J.S., Chen J., Lin M., Culberson C., Sanguinetti M.C. A structural basis for drug-induced long QT syndrome. Proc Natl Acad Sci U S A 2000, 97:12329-12333.
52. Kamiya K., Niwa R., Mitcheson J.S., Sanguinetti M.C. Molecular determinants of HERG channel block. Mol Pharmacol 2006, 69:1709-1716.
53. Perry M., Stansfeld P.J., Leaney J., Wood C., de Groot M.J., Leishman D., et al. Drug binding interactions in the inner cavity of HERG channels: molecular insights from structure-activity relationships of clofilium and ibutilide analogs. Mol Pharmacol 2006, 69:509-519.
54. Perry M.D., deGroot M.J., Helliwell R., Leishman D., Sanguinetti M.C. Structural determinants of HERG channel block by clofilium and ibutilide. Mol Pharmacol 2004, 66:240-249.
55. Chen J., Seebohm G., Sanguinetti M.C. 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 2002, 99:12329-12333.
56. Splawski I., Shen J., Timothy K.W., Lehmann M.H., Priori S., Robinson J.L., et al. Spectrum of mutations in long-QT syndrome genes. KvLQT1, HERG, SCN5A, KCNE1 and KCNE2. Circulation 2000, 102:1175-1185.
57. + channels. J Physiol; 2006, 573:730.291-304.
58. Pless S.A., Galpin J.D., Frankel A., Ahern C.A. Molecular basis for class Ib anti-arrhythmic inhibition of cardiac sodium channels. Nat Commun 2011, 2:351. 10.1038/ncomms1351.
59. Hanck D.A., Nikitina E., McNulty M.M., Fozzard H.A., Lipkind G.M., Sheets M.F. Using lidocaine and benzocaine to link sodium channel molecular conformations to state-dependent antiarrhythmic drug affinity. Circ Res 2009, 105(5):492-499.
60. Tikhonov D.B., Bruhova I., Zhorov B.S. Atomic determinants of state-dependent block of sodium channels by charged local anesthetics and benzocaine. FEBS Lett 2006, 580:6027-6032.
61. Tan Q.Y., Li H.D., Zhu R.H., Zhang Q.Z., Zhang J., Peng W.X. Tolerability and pharmacokinetics of ranolazine following single and multiple sustained release doses in healthy Chinese adult volunteers: a randomized, open-label, Latin square design, phase I study. Am J Cardiovasc Drugs 2013, 13:17-25.
62. Lui H.K., Harris F.J., Chan M.C., Lee G., Mason D.T. Comparison of intravenous mexiletine and lidocaine for the treatment of ventricular arrhythmias. Am Heart J 1986, 112:1153-1158.
63. Silke B., Frais M.A., Verma S.P., Reynolds G.W., Hafizullah M., Kalra P.A., et al. Comparative haemodynamic effects of intravenous lignocaine, disopyramide and flecainide in uncomplicated myocardial infarction. Br J Clin Pharmacol 1986, 22:707-714.
64. Burashnikov A., Di Diego J.M., Zygmunt A.C., Belardinelli L., Antzelevitch C. Atrial-selective sodium channel block as a strategy for suppression of atrial fibrillation. Ann N Y Acad Sci 2008, 1123:105-112.
65. Vizzardi E., D'Aloia A., Quinzani F., Bonadei I., Rovetta R., Bontempi L., et al. A focus on antiarrhythmic properties of ranolazine. J Cardiovasc Pharmacol Ther 2012, 17:353-356.
66. Luderitz B., Mletzko R., Jung W., Manz M. Combination of antiarrhythmic drugs. J Cardiovasc Pharmacol 1991, 17(Suppl. 6):S48-S52.
67. Opincariu M., Varro A., Iost N., Virag L., Hala O., Szolnoki, et al. The cellular electrophysiologic effect of a new amiodarone like antiarrhythmic drug GYKI 16638 in undiseased human ventricular muscle: comparison with sotalol and mexiletine. Curr Med Chem 2002, 9:41-46.
68. Matyus P., Varga I., Rettegi T., Simay A., Kallay N., Karolyhazy L., et al. Novel antiarrhythmic compounds with combined class IB and class III mode of action. Curr Med Chem 2004, 11:61-69.
69. Schimpf R., Wolpert C., Bianchi F., Giustetto C., Gaita F., Bauersfeld U., et al. Congenital short QT syndrome and implantable cardioverter defibrillator treatment: inherent risk for inappropriate shock delivery. J Cardiovasc Electrophysiol 2003, 14:1273-1277.
70. Giustetto C., Schimpf R., Mazzanti A., Scrocco C., Maury P., Anttonen O., et al. Long-term follow-up of patients with short QT syndrome. J Am Coll Cardiol 2011, 58:587-595.