Research Topics
Species | H J WitchelSummaryAffiliation: University of Bristol Country: UK Publications
| Collaborators
|
Detail Information
Publications
Inhibitory actions of the selective serotonin re-uptake inhibitor citalopram on HERG and ventricular L-type calcium currentsHarry J Witchel
Cardiovascular Research Laboratories and Department of Physiology, School of Medical Sciences, Bristol, UK
FEBS Lett 512:59-66. 2002..The effects of citalopram on both calcium current amplitude and the I(Ca,L) 'window' may help to explain citalopram's good cardiac safety profile, given its propensity to block HERG at excessive dosages...
Inhibition of HERG K+ current and prolongation of the guinea-pig ventricular action potential by 4-aminopyridineJ M Ridley
Department of Physiology and Cardiovascular Research Laboratories, School of Medical Sciences, University Walk, Bristol BS8 1TD, UK
J Physiol 549:667-72. 2003..We conclude that by blocking the alpha-subunit of the IKr channel, millimolar concentrations of 4-AP can modulate ventricular repolarisation independently of any action on ITO,1...- Troubleshooting problems with in vitro screening of drugs for QT interval prolongation using HERG K+ channels expressed in mammalian cell lines and Xenopus oocytesHarry J Witchel
Cardiovascular Research Laboratories, Department of Physiology, School of Medical Sciences, University Walk, Bristol BS8 1TD, UK
J Pharmacol Toxicol Methods 48:65-80. 2002..In Xenopus oocytes, endogenous chloride currents, insufficient superfusate flow, diminished HERG current and HERG current 'run up' may create difficulties... - The hERG potassium channel as a therapeutic targetHarry J Witchel
University of Bristol, School of Medical Sciences, Department of Physiology, Bristol, BS8 1TD, UK
Expert Opin Ther Targets 11:321-36. 2007..Future developments will synthesise preclinical data on hERG with other criteria to determine net arrhythmogenic risk. Also, the molecular actions of hERG and its genetics will be elucidated in detail to allow clinical risk reduction... - Psychotropic drugs, cardiac arrhythmia, and sudden deathHarry J Witchel
Department of Physiology and Cardiovascular Research Laboratories, School of Medical Sciences, University of Bristol, Bristol, United Kingdom
J Clin Psychopharmacol 23:58-77. 2003.... - The low-potency, voltage-dependent HERG blocker propafenone--molecular determinants and drug trappingHarry J Witchel
Cardiovascular Research Laboratories and Department of Physiology, School of Medical Sciences, University of Bristol, Bristol, BS8 1TD, UK
Mol Pharmacol 66:1201-12. 2004..This provides further evidence for the existence of gating-induced changes in the spatial location of Phe656 side chains... - Familial and acquired long qt syndrome and the cardiac rapid delayed rectifier potassium currentH J Witchel
Department of Physiology and Cardiovascular Research Laboratories, School of Medical Sciences, University of Bristol, United Kingdom
Clin Exp Pharmacol Physiol 27:753-66. 2000..Until such time, awareness of the QT-prolongation risk of particular agents is important for the clinician... - Time course and voltage dependence of expressed HERG current compared with native "rapid" delayed rectifier K current during the cardiac ventricular action potentialJ C Hancox
Department of Physiology, School of Medical Sciences, University Walk, Bristol, BS8 1TD, UK
Pflugers Arch 436:843-53. 1998.... - Effects of the class III antiarrhythmic agent dofetilide (UK-68,798) on L-type calcium current from rabbit ventricular myocytesA A Paul
Department of Physiology and Cardiovascular Research Laboratories, School of Medical Sciences, Bristol, UK
J Pharm Pharmacol 53:1671-8. 2001..The findings support the notion that dofetilide is a highly selective Class III antiarrhythmic agent, devoid of Class IV antiarrhythmic activity... - Comparative effects of the short QT N588K mutation at 37 degrees C on hERG K+ channel current during ventricular, Purkinje fibre and atrial action potentials: an action potential clamp studyM J McPate
Department of Physiology and Pharmacology, Bristol Heart Institute, School of Medical Sciences, The University of Bristol, University Walk, Bristol, UK
J Physiol Pharmacol 60:23-41. 2009..Changes in the timing of outward I(hERG) transients elicited by premature stimuli following AP commands indicate that SQT1 may alter the protection that hERG provides cardiac tissue against premature arrhythmogenic stimuli... - Pharmacology of the short QT syndrome N588K-hERG K+ channel mutation: differential impact on selected class I and class III antiarrhythmic drugsM J McPate
Cardiovascular Research Laboratories, Department of Physiology and Pharmacology, School of Medical Sciences, University of Bristol, Bristol, UK
Br J Pharmacol 155:957-66. 2008.... - Alteration of HERG current profile during the cardiac ventricular action potential, following a pore mutationJ C Hancox
Department of Physiology, School of Medical Sciences, University of Bristol, United Kingdom
Biochem Biophys Res Commun 253:719-24. 1998..These data provide a direct demonstration that rapid inactivation normally plays a critical role in determining both time-course and voltage dependence of HERG/I(Kr) -current during the cardiac ventricular AP... - Inhibition of the HERG potassium channel by the tricyclic antidepressant doxepinR S Duncan
Department of Physiology and Cardiovascular Research Laboratories, School of Medical Sciences, University Walk, Bristol, BS8 1TD, UK
Biochem Pharmacol 74:425-37. 2007..Notably, this study also establishes doxepin as an effective inhibitor of mutant (N588K) HERG channels responsible for variant 1 of the short QT syndrome... - Potent inhibition of human cardiac potassium (HERG) channels by the anti-estrogen agent clomiphene-without QT interval prolongationKathryn H Yuill
Department of Physiology and Cardiovascular Research Laboratories, School of Medical Sciences, University Walk, Bristol BS8 1TD, UK
Biochem Biophys Res Commun 318:556-61. 2004.... - Preferential closed channel blockade of HERG potassium currents by chemically synthesised BeKm-1 scorpion toxinJames T Milnes
Department of Physiology and Cardiovascular Research Laboratories, School of Medical Sciences, University of Bristol, University Walk, BS8 1TD, Bristol, UK
FEBS Lett 547:20-6. 2003..We conclude that synthetic BeKm-1 toxin blocks HERG preferentially through a closed (resting) state channel blockade mechanism, although some open channel blockade also occurs... - Characterisation of recombinant HERG K+ channel blockade by the Class Ia antiarrhythmic drug procainamideJohn M Ridley
Department of Physiology and Cardiovascular Research Laboratories, School of Medical Sciences, University Walk, BS8 1TD, Bristol, UK
Biochem Biophys Res Commun 306:388-93. 2003..Thus, differences between the chemical structure of PROC and other Class Ia antiarrhythmic drugs may help provide insight into chemical determinants of blocking potency for agents that bind to open/activated HERG channels... - Depleting serotonin enhances both cardiovascular and psychological stress reactivity in recovered patients with anxiety disordersSimon J C Davies
Psychopharmacology Unit, University of Bristol, Whitson Street, Bristol BS1 8NY, United Kingdom
J Clin Psychopharmacol 26:414-8. 2006.... - Tryptophan depletion reverses the therapeutic effect of selective serotonin reuptake inhibitors in social anxiety disorderSpilios V Argyropoulos
Psychopharmacology Unit, University of Bristol, Bristol, United Kingdom
Biol Psychiatry 56:503-9. 2004..This finding supports the notion that SSRIs improve social anxiety by increasing 5-HT availability. The autobiographical script seems to be a more robust challenge test for SAD than the stressful verbal task... - Blockade of HERG potassium currents by fluvoxamine: incomplete attenuation by S6 mutations at F656 or Y652James T Milnes
Department of Physiology and Cardiovascular Research Laboratories, School of Medical Sciences, University Walk, Bristol BS8 1TD, UK
Br J Pharmacol 139:887-98. 2003..Fluvoxamine is therefore quite distinct in this regard from previously studied agents... - Inhibition of the current of heterologously expressed HERG potassium channels by flecainide and comparison with quinidine, propafenone and lignocaineAshok A Paul
Department of Physiology and Cardiovascular Research Laboratories, School of Medical Sciences, University Walk, Bristol, BS8 1TD
Br J Pharmacol 136:717-29. 2002..40 microM. 7. Our data are consistent with FLEC, PROPAF and QUIN exerting I(HERG) blockade at clinically relevant concentrations. The rank potency as HERG blockers of the Class I drugs tested in this study was QUIN=PROPAF>FLEC>>LIG... - hERG1a/1b heteromeric currents exhibit amplified attenuation of inactivation in variant 1 short QT syndromeM J McPate
Department of Physiology and Pharmacology, Bristol Heart Institute, School of Medical Sciences, The University of Bristol, University Walk, Bristol BS8 1TD, UK
Biochem Biophys Res Commun 386:111-7. 2009.... - Disopyramide is an effective inhibitor of mutant HERG K+ channels involved in variant 1 short QT syndromeMark J McPate
Department of Physiology and Cardiovascular Research Laboratories, School of Medical Sciences, University Walk, University of Bristol, BS8 1TD, UK
J Mol Cell Cardiol 41:563-6. 2006..Disopyramide is associated with QT prolongation in normal use and our findings provide a rational basis for its evaluation as a treatment for SQT1... 
Investigating dynamic protocol-dependence of hERG potassium channel inhibition at 37 degrees C: Cisapride versus dofetilideJames T Milnes
Department of Physiology and Pharmacology, School of Medical Sciences, University Walk, Bristol, BS8 1TD, UK
J Pharmacol Toxicol Methods 61:178-91. 2010..Furthermore, it evaluated dynamic (pulse-by-pulse) protocol-dependence of hERG channel inhibition by these drugs...- Erythromycin block of the HERG K+ channel: accessibility to F656 and Y652Rona S Duncan
Department of Physiology and Cardiovascular Research Laboratories, School of Medical Sciences, University of Bristol, University Walk, Bristol BS8 1TD, UK
Biochem Biophys Res Commun 341:500-6. 2006..In computer models of the channel, erythromycin could make several direct contacts with F656, but not with Y652, in the open-state model, and erythromycin was unable to fit into a closed-state channel model... - Clemastine, a conventional antihistamine, is a high potency inhibitor of the HERG K+ channelJohn M Ridley
Department of Physiology and Cardiovascular Research Laboratories, School of Medical Sciences, University Walk, Bristol BS8 1TD, UK
J Mol Cell Cardiol 40:107-18. 2006..The disparity between clemastine's potent IHERG inhibition and a lack of QT-prolongation in normal clinical use underscores the need to interpret HERG IC50 data for novel compounds in the context of information from other safety assays... - The N588K-HERG K+ channel mutation in the 'short QT syndrome': mechanism of gain-in-function determined at 37 degrees CMark J McPate
Department of Physiology and Cardiovascular Research Laboratories, School of Medical Sciences, University Walk, Bristol BS8 1TD, UK
Biochem Biophys Res Commun 334:441-9. 2005.... - High affinity HERG K(+) channel blockade by the antiarrhythmic agent dronedarone: resistance to mutations of the S6 residues Y652 and F656John M Ridley
Department of Physiology and Cardiovascular Research Laboratories, School of Medical Sciences, University Walk, Bristol BS8 1TD, UK
Biochem Biophys Res Commun 325:883-91. 2004..These findings demonstrate that high affinity drug blockade of I(HERG) can occur without a strong dependence on the Y652 and F656 aromatic amino-acid residues... - Lidoflazine is a high affinity blocker of the HERG K(+)channelJohn M Ridley
Department of Physiology and Cardiovascular Research Laboratories, School of Medical Sciences, University Walk, Bristol BS8 1TD, United Kingdom
J Mol Cell Cardiol 36:701-5. 2004.... - Inhibition of ERK and JNK decreases both osmosensitive taurine release and cell proliferation in glioma cellsMark J Belsey
Department of Pharmacology, School of Medical Sciences, University of Bristol, Bristol BS8 1TD, UK
Neurochem Res 32:1940-9. 2007.... - Moderately elevated plasma homocysteine impairs functional endothelial recovery following denudation of mouse carotid arteriesAlastair L Miller
Bristol Heart Institute, University of Bristol, Bristol, UK
Metabolism 53:760-5. 2004..69, P <.003). These data suggest that even modest homocysteinemia has a deleterious effect on the function of healed endothelium in mouse arteries. This may account for its adverse influence on chronic cardiovascular disease... - hERG K+ channel blockade by the antipsychotic drug thioridazine: An obligatory role for the S6 helix residue F656James T Milnes
Department of Physiology and Cardiovascular Research Laboratories, School of Medical Sciences, University Walk, Bristol BS8 1TD, UK
Biochem Biophys Res Commun 351:273-80. 2006.... - Acquired QT interval prolongation and HERG: implications for drug discovery and developmentKeith Finlayson
Fujisawa Institute of Neuroscience in Edinburgh, University of Edinburgh, 1 George Square, Edinburgh EH8 9JZ, UK
Eur J Pharmacol 500:129-42. 2004..Here we review the relationship between HERG, long QT syndrome and TdP, together with a summary of the associated regulatory issues, and developments in pre-clinical screening...