© 1996 American Heart Association, Inc.
Articles |
Class III Antiarrhythmic Drugs Block HERG, a Human Cardiac Delayed Rectifier K+ Channel
Open-Channel Block by Methanesulfonanilides
From the Cardiology Division (P.S.S., M.E.C., M.T.K., M.C.S.), Eccles Program in Human Molecular Biology and Genetics (M.C.S.), Department of Human Genetics (M.E.C., M.T.K.), and Howard Hughes Medical Institute (M.T.K.), University of Utah Health Sciences Center, Salt Lake City.
Correspondence to Michael Sanguinetti, PhD, Cardiology Division, University of Utah Health Sciences Center, Salt Lake City, UT 84112. E-mail mikes@gene1.med.utah.edu.
Abstract We recently reported that mutations in HERG, a potassium channel gene, cause long QT syndrome. Heterologous expression of HERG in Xenopus oocytes revealed that this channel had biophysical properties nearly identical to a cardiac delayed rectifier K+ current, IKr, but had dissimilar pharmacological properties. Class III antiarrhythmic drugs such as E-4031 and MK-499 are potent and specific blockers of IKr in cardiac myocytes. Our initial studies indicated that these compounds did not block HERG at a concentration of 1 µmol/L. In the present study, we used standard two-microelectrode voltage-clamp techniques to further characterize the effects of these drugs on HERG channels expressed in oocytes. Consistent with initial findings, 1 µmol/L MK-499 and E-4031 had no effect on HERG when oocytes were voltage clamped at a negative potential and not pulsed during equilibration with the drug. However, MK-499 did block HERG current if oocytes were repetitively pulsed, or clamped at a voltage positive to the threshold potential for channel activation. This finding is in contrast to previous studies that showed significant block of IKr in isolated myocytes by similar drugs, even in the absence of pulsing. This apparent discrepancy may be due to differences in channel characteristics (HERG versus guinea pig and mouse IKr), tissue (oocytes versus myocytes), or specific drugs. Under steady state conditions, block of HERG by MK-499 was half maximal at 123±12 nmol/L at a test potential of -20 mV. MK-499 (150 nmol/L) did not affect the voltage dependence of activation and rectification nor the kinetics of activation and deactivation of HERG. These data indicate that MK-499 preferentially blocks open HERG channels and further support the conclusion that HERG subunits form IKr channels in cardiac myocytes.
Key Words: HERG • K+ current • class III antiarrhythmic drug • Xenopus oocytes
This article has been cited by other articles:
 |
|
 |
|
  S. Z. Stepanovic, F. Potet, C. I. Petersen, J. A. Smith, J. Meiler, J. R. Balser, and S. Kupershmidt The evolutionarily conserved residue A653 plays a key role in HERG channel closing J. Physiol., June 1, 2009; 587(11): 2555 - 2566. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. B. Ganapathi, M. Kester, and K. S. Elmslie State-dependent block of HERG potassium channels by R-roscovitine: implications for cancer therapy Am J Physiol Cell Physiol, April 1, 2009; 296(4): C701 - C710. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. Hagendorf, D. Fluegge, C. Engelhardt, and M. Spehr Homeostatic Control of Sensory Output in Basal Vomeronasal Neurons: Activity-Dependent Expression of Ether-a-Go-Go-Related Gene Potassium Channels J. Neurosci., January 7, 2009; 29(1): 206 - 221. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 E. J. White, S. J. Park, J. A. Foster, and J. D. Huizinga Ether-a-go-go-related gene 3 is the main candidate for the E-4031-sensitive potassium current in the pacemaker interstitial cells of Cajal Am J Physiol Gastrointest Liver Physiol, October 1, 2008; 295(4): G691 - G699. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 H. Sale, J. Wang, T. J. O'Hara, D. J. Tester, P. Phartiyal, J.-Q. He, Y. Rudy, M. J. Ackerman, and G. A. Robertson Physiological Properties of hERG 1a/1b Heteromeric Currents and a hERG 1b-Specific Mutation Associated With Long-QT Syndrome Circ. Res., September 26, 2008; 103(7): e81 - e95. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
G. C. L. Bett and R. L. Rasmusson Modification of K+ channel-drug interactions by ancillary subunits J. Physiol., February 15, 2008; 586(4): 929 - 950. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 C. C. Canavier, S. A. Oprisan, J. C. Callaway, H. Ji, and P. D. Shepard Computational Model Predicts a Role for ERG Current in Repolarizing Plateau Potentials in Dopamine Neurons: Implications for Modulation of Neuronal Activity J Neurophysiol, November 1, 2007; 98(5): 3006 - 3022. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 E. L. Strevel, D. J. Ing, and L. L. Siu Molecularly Targeted Oncology Therapeutics and Prolongation of the QT Interval J. Clin. Oncol., August 1, 2007; 25(22): 3362 - 3371. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 R. S. Hansen, S.-P. Olesen, and M. Grunnet Pharmacological Activation of Rapid Delayed Rectifier Potassium Current Suppresses Bradycardia-Induced Triggered Activity in the Isolated Guinea Pig Heart J. Pharmacol. Exp. Ther., June 1, 2007; 321(3): 996 - 1002. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. Y. M. Yeung and I. A. Greenwood Pharmacological and biophysical isolation of K+ currents encoded by ether-a-go-go-related genes in murine hepatic portal vein smooth muscle cells Am J Physiol Cell Physiol, January 1, 2007; 292(1): C468 - C476. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 K. Kamiya, R. Niwa, J. S. Mitcheson, and M. C. Sanguinetti Molecular Determinants of hERG Channel Block Mol. Pharmacol., May 1, 2006; 69(5): 1709 - 1716. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. Perry, P. J. Stansfeld, J. Leaney, C. Wood, M. J. de Groot, D. Leishman, M. J. Sutcliffe, and J. S. Mitcheson Drug Binding Interactions in the Inner Cavity of hERG Channels: Molecular Insights from Structure-Activity Relationships of Clofilium and Ibutilide Analogs Mol. Pharmacol., February 1, 2006; 69(2): 509 - 519. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. Rubart and D. P. Zipes Genes and Cardiac Repolarization: The Challenge Ahead Circulation, August 30, 2005; 112(9): 1242 - 1244. [Full Text] [PDF]
|
|
|
|
 |
|
 I. Kim, K. M. Boyle, and J. L. Carroll Postnatal development of E-4031-sensitive potassium current in rat carotid chemoreceptor cells J Appl Physiol, April 1, 2005; 98(4): 1469 - 1477. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
W. Hirdes, M. Schweizer, K. S Schuricht, S. S Guddat, I. Wulfsen, C. K Bauer, and J. R Schwarz Fast erg K+ currents in rat embryonic serotonergic neurones J. Physiol., April 1, 2005; 564(1): 33 - 49. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 C. E. Clancy and R. S. Kass Inherited and Acquired Vulnerability to Ventricular Arrhythmias: Cardiac Na+ and K+ Channels Physiol Rev, January 1, 2005; 85(1): 33 - 47. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
H. J. Witchel, C. E. Dempsey, R. B. Sessions, M. Perry, J. T. Milnes, J. C. Hancox, and J. S. Mitcheson The Low-Potency, Voltage-Dependent HERG Blocker Propafenone--Molecular Determinants and Drug Trapping Mol. Pharmacol., November 1, 2004; 66(5): 1201 - 1212. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J.-S. Bian, A. Kagan, and T. V. McDonald Molecular analysis of PIP2 regulation of HERG and IKr Am J Physiol Heart Circ Physiol, November 1, 2004; 287(5): H2154 - H2163. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 D. Fernandez, A. Ghanta, G. W. Kauffman, and M. C. Sanguinetti Physicochemical Features of the hERG Channel Drug Binding Site J. Biol. Chem., March 12, 2004; 279(11): 10120 - 10127. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. Diochot, E. Loret, T. Bruhn, L. Beress, and M. Lazdunski APETx1, a New Toxin from the Sea Anemone Anthopleura elegantissima, Blocks Voltage-Gated Human Ether-a-go-go-Related Gene Potassium Channels Mol. Pharmacol., July 1, 2003; 64(1): 59 - 69. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 D. Thomas, W. Zhang, K. Wu, A.-B. Wimmer, B. Gut, G. Wendt-Nordahl, S. Kathofer, V. A.W. Kreye, H. A. Katus, W. Schoels, et al. Regulation of HERG potassium channel activation by protein kinase C independent of direct phosphorylation of the channel protein Cardiovasc Res, July 1, 2003; 59(1): 14 - 26. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. M. Farrelly, S. Ro, B. P. Callaghan, M. A. Khoyi, N. Fleming, B. Horowitz, K. M. Sanders, and K. D. Keef Expression and function of KCNH2 (HERG) in the human jejunum Am J Physiol Gastrointest Liver Physiol, June 1, 2003; 284(6): G883 - G895. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
W.S. Redfern, L. Carlsson, A.S. Davis, W.G. Lynch, I. MacKenzie, S. Palethorpe, P.K.S. Siegl, I. Strang, A.T. Sullivan, R. Wallis, et al. 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, April 1, 2003; 58(1): 32 - 45. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
K. Ishii, M. Nagai, M. Takahashi, and M. Endoh Dissociation of E-4031 from the HERG channel caused by mutations of an amino acid results in greater block at high stimulation frequency Cardiovasc Res, March 1, 2003; 57(3): 651 - 659. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. Wang, K. Della Penna, H. Wang, J. Karczewski, T. M. Connolly, K. S. Koblan, P. B. Bennett, and J. J. Salata Functional and pharmacological properties of canine ERG potassium channels Am J Physiol Heart Circ Physiol, January 1, 2003; 284(1): H256 - H267. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J.-B. Park, H. Choe, Y.-K. Lee, K.-C. Ha, K.-S. Rhee, J.-K. Ko, C.-U. Joo, S.-W. Chae, and Y.-G. Kwak Open Channel Block by KCB-328 [1-(2-Amino-4-methanesulfonamidophenoxy)-2-[N-(3,4-dimethoxyphenethyl)-N-methylamino]ethane Hydrochloride] of the Heterologously Expressed Human Ether-a-go-go-Related Gene K+ Channels J. Pharmacol. Exp. Ther., July 1, 2002; 302(1): 314 - 319. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. A. Sanchez-Chapula, R. A. Navarro-Polanco, C. Culberson, J. Chen, and M. C. Sanguinetti Molecular Determinants of Voltage-dependent Human Ether-a-Go-Go Related Gene (HERG) K+ Channel Block J. Biol. Chem., June 21, 2002; 277(26): 23587 - 23595. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
G. A. M. Smith, H.-W. Tsui, E. W. Newell, X. Jiang, X.-P. Zhu, F. W. L. Tsui, and L. C. Schlichter Functional Up-regulation of HERG K+ Channels in Neoplastic Hematopoietic Cells J. Biol. Chem., May 17, 2002; 277(21): 18528 - 18534. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. E O'Leary Inhibition of HERG potassium channels by cocaethylene: a metabolite of cocaine and ethanol Cardiovasc Res, January 1, 2002; 53(1): 59 - 67. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
E. Ficker, W. Jarolimek, and A. M. Brown Molecular Determinants of Inactivation and Dofetilide Block in ether a-go-go (EAG) Channels and EAG-Related K+ Channels Mol. Pharmacol., December 1, 2001; 60(6): 1343 - 1348. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. E. O'Leary Inhibition of Human Ether-A-Go-Go Potassium Channels by Cocaine Mol. Pharmacol., February 1, 2001; 59(2): 269 - 277. [Abstract] [Full Text]
|
|
|
|
|
|
C. A Karle, V. A.W Kreye, D. Thomas, K. Rockl, S. Kathofer, W. Zhang, and J. Kiehn Antiarrhythmic drug carvedilol inhibits HERG potassium channels Cardiovasc Res, February 1, 2001; 49(2): 361 - 370. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
H. Numaguchi, F. M. Mullins, J. P. Johnson Jr., D. C. Johns, S. S. Po, I. C.-H. Yang, G. F. Tomaselli, and J. R. Balser Probing the Interaction Between Inactivation Gating and Dd-Sotalol Block of HERG Circ. Res., November 24, 2000; 87(11): 1012 - 1018. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. S. Mitcheson, J. Chen, M. Lin, C. Culberson, and M. C. Sanguinetti A structural basis for drug-induced long QT syndrome PNAS, September 22, 2000; (2000) 210244497. [Abstract] [Full Text]
|
|
|
|
 |
|
 C.-E. Chiang and D. M. Roden The long QT syndromes: genetic basis and clinical implications J. Am. Coll. Cardiol., July 1, 2000; 36(1): 1 - 12. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
Y. Katayama, A. Fujita, T. Ohe, I. Findlay, and Y. Kurachi Inhibitory Effects of Vesnarinone on Cloned Cardiac Delayed Rectifier K+ Channels Expressed in a Mammalian Cell Line J. Pharmacol. Exp. Ther., July 1, 2000; 294(1): 339 - 346. [Abstract] [Full Text]
|
|
|
|
 |
|
 J. S. Mitcheson, J. Chen, and M. C. Sanguinetti Trapping of a Methanesulfonanilide by Closure of the Herg Potassium Channel Activation Gate J. Gen. Physiol., March 1, 2000; 115(3): 229 - 240. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. P. Lees-Miller, Y. Duan, G. Q. Teng, and H. J. Duff Molecular Determinant of High-Affinity Dofetilide Binding to HERG1 Expressed in Xenopus Oocytes: Involvement of S6 Sites Mol. Pharmacol., February 1, 2000; 57(2): 367 - 374. [Abstract] [Full Text]
|
|
|
|
|
|
H. I. Akbarali, H. Thatte, X. D. He, W. R. Giles, and R. K. Goyal Role of HERG-like K+ currents in opossum esophageal circular smooth muscle Am J Physiol Cell Physiol, December 1, 1999; 277(6): C1284 - C1290. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
D. Thomas, W. Zhang, C. A. Karle, S. Kathofer, W. Schols, W. Kubler, and J. Kiehn Deletion of Protein Kinase A Phosphorylation Sites in the HERG Potassium Channel Inhibits Activation Shift by Protein Kinase A J. Biol. Chem., September 24, 1999; 274(39): 27457 - 27462. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
R. Schafer, I. Wulfsen, S. Behrens, F. Weinsberg, C. K Bauer, and J. R Schwarz The erg-like potassium current in rat lactotrophs J. Physiol., July 15, 1999; 518(2): 401 - 416. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
E. Carmeliet Cardiac Ionic Currents and Acute Ischemia: From Channels to Arrhythmias Physiol Rev, July 1, 1999; 79(3): 917 - 1017. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. Kiehn, A. E. Lacerda, and A. M. Brown Pathways of HERG inactivation Am J Physiol Heart Circ Physiol, July 1, 1999; 277(1): H199 - H210. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
D. J Snyders Structure and function of cardiac potassium channels Cardiovasc Res, May 1, 1999; 42(2): 377 - 390. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. C. Trudeau, S. A. Titus, J. L. Branchaw, B. Ganetzky, and G. A. Robertson Functional Analysis of a Mouse Brain Elk-Type K+ Channel J. Neurosci., April 15, 1999; 19(8): 2906 - 2918. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J.P. Johnson Jr., F. M. Mullins, and P. B. Bennett Human Ether-a-go-go-related Gene K+ Channel Gating Probed with Extracellular Ca2+: Evidence for Two Distinct Voltage Sensors J. Gen. Physiol., April 1, 1999; 113(4): 565 - 580. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
B. Drolet, F. Vincent, J. Rail, M. Chahine, D. Deschênes, S. Nadeau, M. Khalifa, B. A. Hamelin, and J. Turgeon Thioridazine Lengthens Repolarization of Cardiac Ventricular Myocytes by Blocking the Delayed Rectifier Potassium Current J. Pharmacol. Exp. Ther., March 1, 1999; 288(3): 1261 - 1268. [Abstract] [Full Text]
|
|
|
|
|
|
S. Kupershmidt, D. J. Snyders, A. Raes, and D. M. Roden A K+ Channel Splice Variant Common in Human Heart Lacks a C-terminal Domain Required for Expression of Rapidly Activating Delayed Rectifier Current J. Biol. Chem., October 16, 1998; 273(42): 27231 - 27235. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. Kiehn, C. Karle, D. Thomas, X. Yao, J. Brachmann, and W. Kubler HERG Potassium Channel Activation Is Shifted by Phorbol Esters via Protein Kinase A-dependent Pathways J. Biol. Chem., September 25, 1998; 273(39): 25285 - 25291. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
F. Barros, D. Gomez-Varela, C. G Viloria, T. Palomero, T. Giraldez, and P. de la Pena Modulation of human erg K+ channel gating by activation of a G protein-coupled receptor and protein kinase C J. Physiol., September 1, 1998; 511(2): 333 - 346. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
I. M Herzberg, M. C Trudeau, and G. A Robertson Transfer of rapid inactivation and sensitivity to the class III antiarrhythmic drug E-4031 from HERG to M-eag channels J. Physiol., August 15, 1998; 511(1): 3 - 14. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
Z. Zhou, Q. Gong, M. L. Epstein, and C. T. January HERG Channel Dysfunction in Human Long QT Syndrome. INTRACELLULAR TRANSPORT AND FUNCTIONAL DEFECTS J. Biol. Chem., August 14, 1998; 273(33): 21061 - 21066. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
D. Rampe, M. K. Murawsky, J. Grau, and E. W. Lewis The Antipsychotic Agent Sertindole is a High Affinity Antagonist of the Human Cardiac Potassium Channel HERG J. Pharmacol. Exp. Ther., August 1, 1998; 286(2): 788 - 793. [Abstract] [Full Text]
|
|
|
|
|
|
M.-D. Drici, I. Arrighi, C. Chouabe, J. R. Mann, M. Lazdunski, G. Romey, and J. Barhanin Involvement of IsK-Associated K+ Channel in Heart Rate Control of Repolarization in a Murine Engineered Model of Jervell and Lange-Nielsen Syndrome Circ. Res., July 13, 1998; 83(1): 95 - 102. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C. K Bauer The erg inwardly rectifying K+ current and its modulation by thyrotrophin-releasing hormone in giant clonal rat anterior pituitary cells J. Physiol., July 1, 1998; 510(1): 63 - 70. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. Taglialatela, A. Pannaccione, P. Castaldo, G. Giorgio, Z. Zhou, C. T. January, A. Genovese, G. Marone, and L. Annunziato 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., July 1, 1998; 54(1): 113 - 121. [Abstract] [Full Text]
|
|
|
|
|
|
W. Zhou, F. S. Cayabyab, P. S. Pennefather, L. C. Schlichter, and T. E. DeCoursey HERG-like K+ Channels in Microglia J. Gen. Physiol., June 1, 1998; 111(6): 781 - 794. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. Zou, Q. P Xu, and M. C Sanguinetti 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., May 15, 1998; 509(1): 129 - 137. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
E. Ficker, W. Jarolimek, J. Kiehn, A. Baumann, and A. M. Brown Molecular Determinants of Dofetilide Block of HERG K+ Channels Circ. Res., February 23, 1998; 82(3): 386 - 395. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
W. Shi, R. S. Wymore, H.-S. Wang, Z. Pan, I. S. Cohen, D. McKinnon, and J. E. Dixon Identification of Two Nervous System-Specific Members of the erg Potassium Channel Gene Family J. Neurosci., December 15, 1997; 17(24): 9423 - 9432. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
G. Loussouarn, F. Charpentier, R. Mohammad-Panah, K. Kunzelmann, I. Baró, and D. Escande KvLQT1 Potassium Channel but Not IsK Is the Molecular Target for trans-6-Cyano-4-(N-ethylsulfonyl-N-methylamino)-3-hydroxy-2,2-dimethyl-chromane Mol. Pharmacol., December 1, 1997; 52(6): 1131 - 1136. [Abstract] [Full Text]
|
|
|
|
|
|
J. P. Lees-Miller, C. Kondo, L. Wang, and H. J. Duff Electrophysiological Characterization of an Alternatively Processed ERG K+ Channel in Mouse and Human Hearts Circ. Res., November 19, 1997; 81(5): 719 - 726. [Abstract] [Full Text]
|
|
|
|
|
|
B. London, M. C. Trudeau, K. P. Newton, A. K. Beyer, N. G. Copeland, D. J. Gilbert, N. A. J enkins, C. A. Satler, and G. A. Robertson Two Isoforms of the Mouse Ether-a-go-go–Related Gene Coassemble to Form Channels With Properties Similar to the Rapidly Activating Component of the Cardiac Delayed Rectifier K+ Current Circ. Res., November 19, 1997; 81(5): 870 - 878. [Abstract] [Full Text]
|
|
|
|
|
|
M. Taglialatela, P. Castaldo, S. Iossa, A. Pannaccione, A. Fresi, E. Ficker, and L. Annunziato Regulation of the human ether-a-gogo related gene (HERG) K+ channels by reactive oxygen species PNAS, October 14, 1997; 94(21): 11698 - 11703. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C. Fiset, B. Drolet, B. A. Hamelin, and J. Turgeon Block of IKs by the Diuretic Agent Indapamide Modulates Cardiac Electrophysiological Effects of the Class III Antiarrhythmic Drug dl-Sotalol J. Pharmacol. Exp. Ther., October 1, 1997; 283(1): 148 - 156. [Abstract] [Full Text]
|
|
|
|
|
|
T. Yang, D. J. Snyders, and D. M. Roden Rapid Inactivation Determines the Rectification and [K+]o Dependence of the Rapid Component of the Delayed Rectifier K+ Current in Cardiac Cells Circ. Res., June 19, 1997; 80(6): 782 - 789. [Abstract] [Full Text]
|
|
|
|
|
|
R. S. Wymore, G. A. Gintant, R. T. Wymore, J. E. Dixon, D. McKinnon, and I. S. Cohen Tissue and Species Distribution of mRNA for the IKr-like K+ Channel, erg Circ. Res., February 1, 1997; 80(2): 261 - 268. [Abstract] [Full Text]
|
|
|
|
 |
|
 P. D. West, D. K. Martin, J. A. Bursill, K. R. Wyse, and T. J. Campbell Modulation of the Electrophysiologic Actions of E-4031 and Dofetilide by Hyperkalemia and Acidosis in Rabbit Ventricular Myocytes Journal of Cardiovascular Pharmacology and Therapeutics, January 1, 1997; 2(3): 205 - 212. [Abstract] [PDF]
|
|
|
|
|
|
N. K. Jurkiewicz, J. Wang, B. Fermini, M. C. Sanguinetti, and J. J. Salata Mechanism of Action Potential Prolongation by RP 58866 and Its Active Enantiomer, Terikalant: Block of the Rapidly Activating Delayed Rectifier K+ Current, IKr Circulation, December 1, 1996; 94(11): 2938 - 2946. [Abstract] [Full Text]
|
|
|
|
|
|
J. Kiehn, A. E. Lacerda, B. Wible, and A. M. Brown Molecular Physiology and Pharmacology of HERG: Single-Channel Currents and Block by Dofetilide Circulation, November 15, 1996; 94(10): 2572 - 2579. [Abstract] [Full Text]
|
|
|
|
|
|
D. M. Roden, R. Lazzara, M. Rosen, P. J. Schwartz, J. Towbin, and G. M. Vincent Multiple Mechanisms in the Long-QT Syndrome: Current Knowledge, Gaps, and Future Directions Circulation, October 15, 1996; 94(8): 1996 - 2012. [Abstract] [Full Text]
|
|
|
|
|
|
M.-L. Roy, R. Dumaine, and A. M. Brown HERG, a Primary Human Ventricular Target of the Nonsedating Antihistamine Terfenadine Circulation, August 15, 1996; 94(4): 817 - 823. [Abstract] [Full Text]
|
|
|
|
|
|
J. S. Mitcheson, J. Chen, M. Lin, C. Culberson, and M. C. Sanguinetti A structural basis for drug-induced long QT syndrome PNAS, October 24, 2000; 97(22): 12329 - 12333. [Abstract] [Full Text] [PDF]
|
|