Dierk Thomas

Summary

Affiliation: University of Heidelberg
Country: Germany

Publications

  1. pmc Systemic Embolization and Myocardial Infarction due to Clinically Unrecognized Left Atrial Myxoma
    Britta Vogel
    Department of Cardiology, Medical University Hospital Heidelberg, Im Neuenheimer Feld 410, 69120 Heidelberg, Germany
    Case Report Med 2011:159024. 2011
  2. pmc Acute effects of dronedarone on both components of the cardiac delayed rectifier K+ current, HERG and KvLQT1/minK potassium channels
    Dierk Thomas
    Department of Cardiology, Medical University Hospital Heidelberg, Bergheimerstrasse 58, Heidelberg D 69115, Germany
    Br J Pharmacol 140:996-1002. 2003
  3. ncbi Radiation therapy-induced electrical reset of an implantable cardioverter defibrillator device located outside the irradiation field
    Dierk Thomas
    Department of Cardiology, Medical University Hospital Heidelberg, Heidelberg, Germany
    J Electrocardiol 37:73-4. 2004
  4. ncbi Inhibition of human ether-a-go-go-related gene potassium channels by alpha 1-adrenoceptor antagonists prazosin, doxazosin, and terazosin
    Dierk Thomas
    Department of Cardiology, Medical University Hospital Heidelberg, Bergheimerstrasse 58, 69115, Heidelberg, Germany
    Naunyn Schmiedebergs Arch Pharmacol 369:462-72. 2004
  5. ncbi Defective protein trafficking in hERG-associated hereditary long QT syndrome (LQT2): molecular mechanisms and restoration of intracellular protein processing
    Dierk Thomas
    Department of Cardiology, Medical University Hospital Heidelberg, Bergheimerstrasse 58, D 69115 Heidelberg, Germany
    Cardiovasc Res 60:235-41. 2003
  6. ncbi Modulation of HERG potassium channel function by drug action
    Dierk Thomas
    Department of Cardiology, Medical University Hospital Heidelberg, Bergheimerstrasse 58, D 69115 Heidelberg, Germany
    Ann Med 36:41-6. 2004
  7. ncbi Adrenergic regulation of the rapid component of the cardiac delayed rectifier potassium current, I(Kr), and the underlying hERG ion channel
    Dierk Thomas
    Department of Cardiology, Medical University Hospital Heidelberg, Bergheimer Strasse 58
    Basic Res Cardiol 99:279-87. 2004
  8. ncbi Activation of cardiac human ether-a-go-go related gene potassium currents is regulated by alpha(1A)-adrenoceptors
    Dierk Thomas
    Department of Cardiology, Medical University Hospital, Im Neuenheimer Feld 410, 69120, Heidelberg, Germany
    J Mol Med (Berl) 82:826-37. 2004
  9. pmc Inhibition of cardiac HERG currents by the DNA topoisomerase II inhibitor amsacrine: mode of action
    Dierk Thomas
    Department of Cardiology, Medical University Hospital Heidelberg, Germany
    Br J Pharmacol 142:485-94. 2004
  10. ncbi Inhibition of cloned HERG potassium channels by the antiestrogen tamoxifen
    Dierk Thomas
    Department of Cardiology, Medical University Hospital Heidelberg, Bergheimerstrasse 58, 69115 Heidelberg, Germany
    Naunyn Schmiedebergs Arch Pharmacol 368:41-8. 2003

Collaborators

Detail Information

Publications76

  1. pmc Systemic Embolization and Myocardial Infarction due to Clinically Unrecognized Left Atrial Myxoma
    Britta Vogel
    Department of Cardiology, Medical University Hospital Heidelberg, Im Neuenheimer Feld 410, 69120 Heidelberg, Germany
    Case Report Med 2011:159024. 2011
    ..In summary, early diagnostic differentiation of myxoma from vasculitis is critical, and immediate surgical removal of myxoma is required as the probability of thromboembolic complications increases over time...
  2. pmc Acute effects of dronedarone on both components of the cardiac delayed rectifier K+ current, HERG and KvLQT1/minK potassium channels
    Dierk Thomas
    Department of Cardiology, Medical University Hospital Heidelberg, Bergheimerstrasse 58, Heidelberg D 69115, Germany
    Br J Pharmacol 140:996-1002. 2003
    ....
  3. ncbi Radiation therapy-induced electrical reset of an implantable cardioverter defibrillator device located outside the irradiation field
    Dierk Thomas
    Department of Cardiology, Medical University Hospital Heidelberg, Heidelberg, Germany
    J Electrocardiol 37:73-4. 2004
    ..This case report highlights the diagnostic challenge represented by the environment of therapeutic radiation...
  4. ncbi Inhibition of human ether-a-go-go-related gene potassium channels by alpha 1-adrenoceptor antagonists prazosin, doxazosin, and terazosin
    Dierk Thomas
    Department of Cardiology, Medical University Hospital Heidelberg, Bergheimerstrasse 58, 69115, Heidelberg, Germany
    Naunyn Schmiedebergs Arch Pharmacol 369:462-72. 2004
    ..These data may provide a hypothetical molecular explanation for the apoptotic effect of quinazoline-derived alpha1-adrenoceptor antagonists...
  5. ncbi Defective protein trafficking in hERG-associated hereditary long QT syndrome (LQT2): molecular mechanisms and restoration of intracellular protein processing
    Dierk Thomas
    Department of Cardiology, Medical University Hospital Heidelberg, Bergheimerstrasse 58, D 69115 Heidelberg, Germany
    Cardiovasc Res 60:235-41. 2003
    ..This review summarizes the current knowledge on hERG channel trafficking under physiological and pathological conditions. In addition, therapeutic approaches to restore normal hERG trafficking in vitro and in vivo are discussed...
  6. ncbi Modulation of HERG potassium channel function by drug action
    Dierk Thomas
    Department of Cardiology, Medical University Hospital Heidelberg, Bergheimerstrasse 58, D 69115 Heidelberg, Germany
    Ann Med 36:41-6. 2004
    ..In conclusion, the increasing understanding of the molecular mechanisms that underlie HERG channel block by antiarrhythmic and non-antiarrhythmic drugs may improve prevention and treatment of drug-induced long-QT syndrome...
  7. ncbi Adrenergic regulation of the rapid component of the cardiac delayed rectifier potassium current, I(Kr), and the underlying hERG ion channel
    Dierk Thomas
    Department of Cardiology, Medical University Hospital Heidelberg, Bergheimer Strasse 58
    Basic Res Cardiol 99:279-87. 2004
    ..This review summarizes the current knowledge on hERG/I(Kr) channel modulation by adrenergic activity. In addition, therapeutic approaches to future effective, more genotype-specific antiarrhythmic therapies are discussed...
  8. ncbi Activation of cardiac human ether-a-go-go related gene potassium currents is regulated by alpha(1A)-adrenoceptors
    Dierk Thomas
    Department of Cardiology, Medical University Hospital, Im Neuenheimer Feld 410, 69120, Heidelberg, Germany
    J Mol Med (Berl) 82:826-37. 2004
    ..This novel regulatory pathway of alpha1-adrenergic hERG current regulation provides a link between stress and ventricular arrhythmias, in particular in patients with heart disease...
  9. pmc Inhibition of cardiac HERG currents by the DNA topoisomerase II inhibitor amsacrine: mode of action
    Dierk Thomas
    Department of Cardiology, Medical University Hospital Heidelberg, Germany
    Br J Pharmacol 142:485-94. 2004
    ....
  10. ncbi Inhibition of cloned HERG potassium channels by the antiestrogen tamoxifen
    Dierk Thomas
    Department of Cardiology, Medical University Hospital Heidelberg, Bergheimerstrasse 58, 69115 Heidelberg, Germany
    Naunyn Schmiedebergs Arch Pharmacol 368:41-8. 2003
    ..This study demonstrates that HERG potassium channels are blocked by the antiestrogenic drug tamoxifen. We conclude that HERG current inhibition might be an explanation for the QT interval prolongation associated with this drug...
  11. ncbi Direct block of hERG potassium channels by the protein kinase C inhibitor bisindolylmaleimide I (GF109203X)
    Dierk Thomas
    Department of Cardiology, Medical University Hospital Heidelberg, Im Neuenheimer Feld 410, D 69120 Heidelberg, Germany
    Cardiovasc Res 64:467-76. 2004
    ..The direct interaction of the commonly used protein kinase C (PKC) inhibitor bisindolylmaleimide I (BIM I) with hERG, KvLQT1/minK, and I(Kr) currents was investigated in this study...
  12. ncbi Regulation of HERG potassium channel activation by protein kinase C independent of direct phosphorylation of the channel protein
    Dierk Thomas
    Department of Cardiology, Medical University Hospital Heidelberg, Bergheimerstrasse 58, D 69115 Heidelberg, Germany
    Cardiovasc Res 59:14-26. 2003
    ..The aim of the present study was to elucidate the biochemical pathways of the protein kinase C (PKC)-dependent regulation of HERG currents...
  13. ncbi Protein kinase A-mediated phosphorylation of HERG potassium channels in a human cell line
    Zhang Wei
    Department of Cardiology, Medical University Hospital Heidelberg, Heidelberg, Germany
    Chin Med J (Engl) 115:668-76. 2002
    ..To investigate the molecular mechanism of human ether-a-go-go-related gene (HERG) potassium channels regulated by protein kinase A (PKA) in a human cell line...
  14. ncbi Regulation of cardiac inwardly rectifying potassium current IK1 and Kir2.x channels by endothelin-1
    Claudia Kiesecker
    Department of Cardiology, Medical University Hospital Heidelberg, Im Neuenheimer Feld 410, 69120 Heidelberg, Germany
    J Mol Med (Berl) 84:46-56. 2006
    ..2 channel subunits and additional regulatory effects on Kir2.3 channels. This mechanism may contribute to the intrinsic arrhythmogenic potential of ET-1...
  15. doi The human cardiac K2P3.1 (TASK-1) potassium leak channel is a molecular target for the class III antiarrhythmic drug amiodarone
    Jakob Gierten
    Department of Cardiology, Medical University Hospital Heidelberg, Im Neuenheimer Feld 410, 69120, Heidelberg, Germany
    Naunyn Schmiedebergs Arch Pharmacol 381:261-70. 2010
    ..1 may cause prolongation of cardiac repolarization and action potential duration in patients with high individual plasma concentrations, possibly contributing to the antiarrhythmic efficacy of the class III drug...
  16. ncbi Inhibition of cardiac HERG potassium channels by the atypical antidepressant trazodone
    Edgar Zitron
    Department of Internal Medicine III Cardiology, Medical University Hospital Heidelberg, Bergheimerstrasse 58, 69115, Heidelberg, Germany
    Naunyn Schmiedebergs Arch Pharmacol 370:146-56. 2004
    ..In summary, the atypical antidepressant trazodone blocks cardiac HERG channels at concentrations that are probably relevant in vivo, particularly in overdosage...
  17. ncbi Drug binding to aromatic residues in the HERG channel pore cavity as possible explanation for acquired Long QT syndrome by antiparkinsonian drug budipine
    Eberhard P Scholz
    3rd Department of Internal Medicine Cardiology, University of Heidelberg Medical School, Bergheimerstrasse 58, 69115, Heidelberg, Germany
    Naunyn Schmiedebergs Arch Pharmacol 368:404-14. 2003
    ..Furthermore, these findings underline the importance of the aromatic residues Y652 and F656 in the binding of lipophilic drugs to HERG channels...
  18. ncbi Human cardiac inwardly rectifying current IKir2.2 is upregulated by activation of protein kinase A
    Edgar Zitron
    Department of Cardiology, Medical University Hospital Heidelberg, Bergheimerstrasse 58, D 69115, Heidelberg, Germany
    Cardiovasc Res 63:520-7. 2004
    ..Protein kinases A (PKA) and C (PKC) are key enzymes in adrenergic signal transduction, inducing arrhythmias in heart disease. This study investigated the regulation of Kir2.2 (KCNJ12) by PKA...
  19. doi Identification and functional characterization of zebrafish K(2P)10.1 (TREK2) two-pore-domain K(+) channels
    Jakob Gierten
    Department of Cardiology, Medical University Hospital Heidelberg, Im Neuenheimer Feld 410, D 69120 Heidelberg, Germany
    Biochim Biophys Acta 1818:33-41. 2012
    ..1 two-pore-domain K(+) channels that exhibit structural and functional properties largely similar to human K(2P)10.1. We conclude that the zebrafish represents a valid model to study K(2P)10.1 function in vivo...
  20. doi Inhibition of cardiac hERG potassium channels by tetracyclic antidepressant mianserin
    Daniel Scherer
    Department of Internal Medicine III Cardiology, University Hospital Heidelberg, Im Neuenheimer Feld 410, D 69120, Heidelberg, Germany
    Naunyn Schmiedebergs Arch Pharmacol 378:73-83. 2008
    ..Therefore, in patients with complex co-medication (i.e., additional hERG-blocking agents) and in patients with risk factors for acquired long QT syndrome as well as in cases of overdose, adequate monitoring should be recommended...
  21. doi Genetic suppression of atrial fibrillation using a dominant-negative ether-a-go-go-related gene mutant
    Radim Soucek
    Department of Cardiology, University of Heidelberg, Heidelberg, Germany
    Heart Rhythm 9:265-72. 2012
    ..Atrial fibrillation (AF) is the most common sustained cardiac arrhythmia. Gene therapy-dependent modulation of atrial electrophysiology may provide a more specific alternative to pharmacological and ablative treatment strategies...
  22. doi Genetic suppression of Gαs protein provides rate control in atrial fibrillation
    Patrick Lugenbiel
    Department of Cardiology, University of Heidelberg, Medical University Hospital, Germany
    Basic Res Cardiol 107:265. 2012
    ..Rate control by gene therapy may provide an alternative to current pharmacological treatment of AF...
  23. doi Biophysical characterization of KCNQ1 P320 mutations linked to long QT syndrome 1
    Dierk Thomas
    Department of Cardiology, Medical University Hospital Heidelberg, Im Neuenheimer Feld 410, D 69120 Heidelberg, Germany
    J Mol Cell Cardiol 48:230-7. 2010
    ..This study emphasizes the significance of mutation screening for diagnosis, risk-assessment, and mutation-site specific management in LQTS patients...
  24. ncbi Inhibition of cardiac HERG channels by grapefruit flavonoid naringenin: implications for the influence of dietary compounds on cardiac repolarisation
    Eberhard P Scholz
    Department of Cardiology, Medical University Hospital Heidelberg, Im Neuenheimer Feld 410, 69120 Heidelberg, Germany
    Naunyn Schmiedebergs Arch Pharmacol 371:516-25. 2005
    ..This may have important implications for phytotherapy and for dietary recommendations for cardiologic patients. Therefore, electrophysiological effects of flavonoids deserve further investigation...
  25. ncbi In vitro modulation of HERG channels by organochlorine solvent trichlormethane as potential explanation for proarrhythmic effects of chloroform
    Eberhard P Scholz
    3rd Department of Internal Medicine Cardiology, Medical University Hospital Heidelberg, Im Neuenheimer Feld 410, 69120 Heidelberg, Germany
    Toxicol Lett 165:156-66. 2006
    ..In summary, chloroform blocked HERG potassium channels probably in a toxicologically relevant concentration. These findings contribute to the pathophysiology of proarrhythmic effects in acute chloroform intoxication...
  26. ncbi Kir2.x inward rectifier potassium channels are differentially regulated by adrenergic alpha1A receptors
    Edgar Zitron
    Department of Cardiology, Medical University Hospital Heidelberg, Im Neuenheimer Feld 410, D 69120 Heidelberg, Germany
    J Mol Cell Cardiol 44:84-94. 2008
    ..Src tyrosine kinase pathways are essential for the inhibition of native I(K1) current by adrenergic alpha(1) receptors. This regulation may contribute to arrhythmogenesis under adrenergic stimulation...
  27. ncbi Human cardiac inwardly-rectifying K+ channel Kir(2.1b) is inhibited by direct protein kinase C-dependent regulation in human isolated cardiomyocytes and in an expression system
    Christoph A Karle
    Department of Cardiology, University of Heidelberg Medical School, Heidelberg, Germany
    Circulation 106:1493-9. 2002
    ..The native inward rectifier potassium current (IK1) plays a central role in the stabilization of the resting membrane potential and the process of arrhythmogenesis. This study investigates the functional relationship between PKC and IK1...
  28. ncbi Human beta(3)-adrenoreceptors couple to KvLQT1/MinK potassium channels in Xenopus oocytes via protein kinase C phosphorylation of the KvLQT1 protein
    Sven Kathofer
    Department of Cardiology, Medical University Hospital Heidelberg, Bergheimerstrasse 58, 69115, Heidelberg, Germany
    Naunyn Schmiedebergs Arch Pharmacol 368:119-26. 2003
    ..Our results suggest that the regulation of the KvLQT1/MinK potassium channel via beta(3)-AR is substantially mediated by PKC phosphorylation of the KvLQT1 protein at its four C-terminal PKC phosphorylation sites...
  29. ncbi Activation of inwardly rectifying Kir2.x potassium channels by beta 3-adrenoceptors is mediated via different signaling pathways with a predominant role of PKC for Kir2.1 and of PKA for Kir2.2
    Daniel Scherer
    Department of Cardiology, Medical University Hospital Heidelberg, Im Neuenheimer Feld 410, 69120, Heidelberg, Germany
    Naunyn Schmiedebergs Arch Pharmacol 375:311-22. 2007
    ..2 subunits. This regulation may contribute to the hyperpolarizing effects of beta(3)-adrenoceptors in tissues that exhibit modulation by Kir2 channel function...
  30. doi Cardiac expression and atrial fibrillation-associated remodeling of K₂p2.1 (TREK-1) K⁺ channels in a porcine model
    Constanze Schmidt
    Department of Cardiology, Medical University Hospital, Im Neuenheimer Feld 410, D 69120 Heidelberg, Germany
    Life Sci 97:107-15. 2014
    ..This study was designed to identify and functionally express porcine K2P2.1 channels. In addition, we sought to analyze cardiac expression and AF-associated K2P2.1 remodeling in a clinically relevant porcine AF model...
  31. ncbi Atypical tetracyclic antidepressant maprotiline is an antagonist at cardiac hERG potassium channels
    Claudia Kiesecker
    Department of Cardiology, Medical University Hospital Heidelberg, Im Neuenheimer Feld 350, 69120, Heidelberg, Germany
    Naunyn Schmiedebergs Arch Pharmacol 373:212-20. 2006
    ..Although the affinity of maprotiline to hERG channels is low, its use in patients with risk factors for acquired long QT syndrome should be monitored appropriately...
  32. ncbi QTc prolongation by grapefruit juice and its potential pharmacological basis: HERG channel blockade by flavonoids
    Edgar Zitron
    Department of Cardiology, University of Heidelberg Medical School, Heidelberg, Germany
    Circulation 111:835-8. 2005
    ..The effects of flavonoids on cardiac electrophysiology, which theoretically may have both antiarrhythmic and proarrhythmic consequences, have not been studied systematically to date...
  33. doi Novel electrophysiological properties of dronedarone: inhibition of human cardiac two-pore-domain potassium (K2P) channels
    Constanze Schmidt
    Department of Cardiology, Medical University Hospital, Heidelberg, Im Neuenheimer Feld 410, 69120, Heidelberg, Germany
    Naunyn Schmiedebergs Arch Pharmacol 385:1003-16. 2012
    ..1 currents. K(2P) current inhibition by dronedarone represents a previously unrecognized mechanism of action that extends the multichannel blocking profile of the drug...
  34. doi Suppression of persistent atrial fibrillation by genetic knockdown of caspase 3: a pre-clinical pilot study
    Kerstin Trappe
    Department of Cardiology, University of Heidelberg, Im Neuenheimer Feld 410, 69120 Heidelberg, Germany
    Eur Heart J 34:147-57. 2013
    ..We hypothesized that genetic suppression of an apoptotic key enzyme, caspase 3, would prevent the development of persistent AF by reducing apoptosis which may serve as an arrhythmogenic substrate...
  35. ncbi Class Ia anti-arrhythmic drug ajmaline blocks HERG potassium channels: mode of action
    Claudia Kiesecker
    Department of Cardiology, University of Heidelberg Medical School, Bergheimerstrasse 58, 69115 Heidelberg, Germany
    Naunyn Schmiedebergs Arch Pharmacol 370:423-35. 2004
    ..Therefore, inhibitory effects on HERG channels may contribute to both the high anti-arrhythmic efficacy of ajmaline and to its pro-arrhythmic potential...
  36. ncbi The antidepressant drug fluoxetine is an inhibitor of human ether-a-go-go-related gene (HERG) potassium channels
    Dierk Thomas
    Department of Cardiology, Medical University Hospital Heidelberg, Heidelberg, Germany
    J Pharmacol Exp Ther 300:543-8. 2002
    ..We conclude that HERG current inhibition might be an explanation for the arrhythmogenic side effects of this drug...
  37. doi Class I antiarrhythmic drugs inhibit human cardiac two-pore-domain K(+) (K2 ₂p) channels
    Constanze Schmidt
    Department of Cardiology, Medical University Hospital Heidelberg, Im Neuenheimer Feld 410, D 69120 Heidelberg, Germany
    Eur J Pharmacol 721:237-48. 2013
    ..In summary, class I antiarrhythmic drugs target cardiac K2P K(+) channels. Blockade of hK2P2.1 and hK2P3.1 potassium currents provides mechanistic evidence to establish cardiac K2P channels as antiarrhythmic drug targets. ..
  38. pmc PKC-dependent activation of human K(2P) 18.1 K(+) channels
    Ann Kathrin Rahm
    Department of Cardiology, Medical University Hospital Heidelberg, Heidelberg, Germany
    Br J Pharmacol 166:764-73. 2012
    ..1 has been implicated in migraine, and activation of K(2P) 18.1 channels was proposed as a therapeutic strategy. Here we elucidated the molecular mechanisms underlying PKC-dependent activation of K(2P) 18.1 currents...
  39. ncbi The antiarrhythmic drug BRL-32872
    Christoph A Karle
    Department of Cardiology, Medical University Hospital Heidelberg, Heidelberg, Germany
    Cardiovasc Drug Rev 20:111-20. 2002
    ..In the ischemic hearts of animals the drug significantly reduced early afterdepolarization and ventricular tachycardia. The antiarrhythmic effect of BRL-32872 has not yet been demonstrated in humans...
  40. pmc Transcription profiling of HCN-channel isotypes throughout mouse cardiac development
    Patrick A Schweizer
    Universitatsklinikum Heidelberg, Innere Medizin III, Im Neuenheimer Feld 410, 69120 Heidelberg, Germany
    Basic Res Cardiol 104:621-9. 2009
    ..Furthermore, constantly low HCN transcription in adult myocardium may be required to prevent atrial and ventricular arrhythmogenesis...
  41. pmc The antipsychotic drug chlorpromazine inhibits HERG potassium channels
    Dierk Thomas
    Department of Cardiology, Medical University Hospital Heidelberg, Bergheimerstrasse 58, D 69115 Heidelberg, Germany
    Br J Pharmacol 139:567-74. 2003
    ..6) In conclusion, HERG channels were blocked in the closed and activated states, and unblocking occurred very slowly...
  42. ncbi Green tea flavonoid epigallocatechin-3-gallate (EGCG) inhibits cardiac hERG potassium channels
    Kamilla Kelemen
    Department of Internal Medicine III Cardiology, Medical University Hospital Heidelberg, Im Neuenheimer Feld 410, 69120 Heidelberg, Germany
    Biochem Biophys Res Commun 364:429-35. 2007
    ..In conclusion, EGCG is a low-affinity inhibitor of hERG sharing major electrophysiological features with pharmaceutical hERG antagonists...
  43. ncbi Orange flavonoid hesperetin modulates cardiac hERG potassium channel via binding to amino acid F656
    Eberhard P Scholz
    Department of Cardiology, Medical University Hospital Heidelberg, Im Neuenheimer Feld 410, D 69120 Heidelberg, Germany
    Nutr Metab Cardiovasc Dis 17:666-75. 2007
    ..HERG potassium channels play a major role in cardiac repolarisation and represent the most important pharmacologic target of both antiarrhythmic and proarrhythmic drugs...
  44. doi Anti-KCNQ1 K⁺ channel autoantibodies increase IKs current and are associated with QT interval shortening in dilated cardiomyopathy
    Jin Li
    Department of Cardiology, University Hospital of Heidelberg, Im Neuenheimer Feld 410, Heidelberg 69120, Germany
    Cardiovasc Res 98:496-503. 2013
    ..The purpose of this pilot study was to characterize ion channel autoantibodies in DCM targeting the cardiac repolarizing K(+) current, IKs, and the underlying KCNQ1 potassium channel...
  45. doi Impaired ion channel function related to a common KCNQ1 mutation - implications for risk stratification in long QT syndrome 1
    Parwez Aidery
    Department of Cardiology, University of Heidelberg, Im Neuenheimer Feld 410, D 69120 Heidelberg, Germany
    Gene 511:26-33. 2012
    ..However, the index patient and other mutation carriers were asymptomatic, highlighting potential limitations of risk assessment schemes based on ion channel data...
  46. doi Multiple mechanisms of hERG liability: K+ current inhibition, disruption of protein trafficking, and apoptosis induced by amoxapine
    Sabrina Obers
    Department of Cardiology, Medical University Hospital Heidelberg, Im Neuenheimer Feld 410, 69120 Heidelberg, Germany
    Naunyn Schmiedebergs Arch Pharmacol 381:385-400. 2010
    ..Further experiments are required to validate a specific pro-apoptotic effect mediated through blockade of hERG channels...
  47. ncbi Anticholinergic antiparkinson drug orphenadrine inhibits HERG channels: block attenuation by mutations of the pore residues Y652 or F656
    Eberhard P Scholz
    Department of Internal Medicine III, University Hospital Heidelberg, Im Neuenheimer Feld 410, 69120, Heidelberg, Germany
    Naunyn Schmiedebergs Arch Pharmacol 376:275-84. 2007
    ..In conclusion, we show that the anticholinergic agent orphenadrine is an antagonist at HERG channels. These results provide a novel molecular basis for the reported proarrhythmic side effects of orphenadrine...
  48. ncbi Aquaporin-1 channel function is positively regulated by protein kinase C
    Wei Zhang
    Department of Cardiology, University Hospital Heidelberg, D 69120 Heidelberg, Germany
    J Biol Chem 282:20933-40. 2007
    ....
  49. pmc Bertosamil blocks HERG potassium channels in their open and inactivated states
    Edgar Zitron
    3rd Department of Internal Medicine Cardiology, University of Heidelberg Medical School, Heidelberg, Germany
    Br J Pharmacol 137:221-8. 2002
    ..6. In summary, bertosamil blocked the HERG potassium channel. These blocking properties may contribute to the anti-arrhythmic effects of bertosamil in the treatment of atrial and particular ventricular arrhythmias...
  50. ncbi Dominant-negative I(Ks) suppression by KCNQ1-deltaF339 potassium channels linked to Romano-Ward syndrome
    Dierk Thomas
    Universitätsklinik Heidelberg, Innere Medizin III, Im Neuenheimer Feld 410, 69120 Heidelberg, Germany
    Cardiovasc Res 67:487-97. 2005
    ..In this study, we investigate and discuss dominant-negative I(Ks) current reduction by a KCNQ1 deletion mutation identified in a RWS family...
  51. pmc Selective noradrenaline reuptake inhibitor atomoxetine directly blocks hERG currents
    Daniel Scherer
    Department of Internal Medicine III, University Hospital Heidelberg, Im Neuenheimer Feld 410, Heidelberg, Germany
    Br J Pharmacol 156:226-36. 2009
    ..We therefore analysed acute and subacute effects of atomoxetine on cloned human Ether-à-Go-Go-Related Gene (hERG) channels...
  52. doi Biophysical properties of zebrafish ether-à-go-go related gene potassium channels
    Eberhard P Scholz
    Department of Internal Medicine III, University Hospital Heidelberg, Im Neuenheimer Feld 410, 69120 Heidelberg, Germany
    Biochem Biophys Res Commun 381:159-64. 2009
    ..Considering the conserved channel function, the zebrafish represents a valuable model to investigate human ERG channel related diseases...
  53. doi Inhibition of cardiac Kir2.1-2.3 channels by beta3 adrenoreceptor antagonist SR 59230A
    Martin Kulzer
    Department of Cardiology, University Hospital Heidelberg, Germany
    Biochem Biophys Res Commun 424:315-20. 2012
    ..These findings establish SR59230A as a novel inhibitor of Kir2.1-2.3 channels with a favorable profile with respect to additional effects on other cardiac repolarizing potassium channels...
  54. doi Initial experience with robotic navigation for catheter ablation of paroxysmal and persistent atrial fibrillation
    Dierk Thomas
    Department of Cardiology, Medical University Hospital Heidelberg, Heidelberg, Germany
    J Electrocardiol 45:95-101. 2012
    ..Here, we assess procedural parameters of AF ablation obtained during initial use of RRN compared with a control group treated with a manual ablation approach...
  55. doi Identification and functional characterization of the novel human ether-a-go-go-related gene (hERG) R744P mutant associated with hereditary long QT syndrome 2
    Parwez Aidery
    Department of Cardiology, University of Heidelberg, Im Neuenheimer Feld 410, D 69120 Heidelberg, Germany
    Biochem Biophys Res Commun 418:830-5. 2012
    ..The functional defect associated with hERG R744P serves as molecular basis for LQTS in the index patient...
  56. pmc Alternative splicing determines mRNA translation initiation and function of human K(2P)10.1 K+ channels
    Kathrin Staudacher
    Department of Cardiology, Medical University Hospital Heidelberg, Im Neuenheimer Feld 410, D 69120 Heidelberg, Germany
    J Physiol 589:3709-20. 2011
    ..1 channels. The interaction between hK(2P)10.1 mRNA splicing, translation and function increases K+ channel complexity and is expected to contribute to electrophysiological plasticity of excitable cells...
  57. doi Connexin 43 gene therapy prevents persistent atrial fibrillation in a porcine model
    Olympia Bikou
    Department of Cardiology, Medical University Hospital, Im Neuenheimer Feld 410, Heidelberg D 69120, Germany
    Cardiovasc Res 92:218-25. 2011
    ..The first aim of this study was to assess whether AF is associated with connexin remodelling in a porcine model. A strategy to suppress persistent AF by gene therapy was then developed and evaluated in vivo...
  58. ncbi Skipping of Exon 1 in the KCNQ1 gene causes Jervell and Lange-Nielsen syndrome
    Joerg Zehelein
    Universitatsklinikum Heidelberg, Innere Medizin III, Im Neuenheimer Feld 410, 69120 Heidelberg, Germany
    J Biol Chem 281:35397-403. 2006
    ..These data suggest mechanisms that prevent production of truncated KCNQ1 channel subunits in cardiomyocytes of individuals heterozygous for the mutant allele...
  59. pmc Efficacy, High Procedural Safety And Rapid Optimization Of Cryoballoon Atrial Fibrillation Ablation In The Hands Of A New Operator
    Eberhard Scholz
    Department of Cardiology, Medical University Hospital, Im Neuenheimer Feld 410, 69120 Heidelberg, Germany
    J Atr Fibrillation 8:1341. 2016
    ..Cryoballoon (CB) ablation is successful in eliminating atrial fibrillation (AF)...
  60. doi Therapeutic targeting of two-pore-domain potassium (K(2P)) channels in the cardiovascular system
    Felix Wiedmann
    Department of Cardiology, University of Heidelberg, Im Neuenheimer Feld 410, 69120 Heidelberg, Germany
    Clin Sci (Lond) 130:643-50. 2016
    ..The function, regulation and clinical significance of cardiovascular K(2P) channels are summarized in the present review, and therapeutic options are emphasized...
  61. doi Functional characterization of zebrafish K2P18.1 (TRESK) two-pore-domain K+ channels
    Ann Kathrin Rahm
    Department of Cardiology, Medical University Hospital Heidelberg, Im Neuenheimer Feld 410, 69120, Heidelberg, Germany
    Naunyn Schmiedebergs Arch Pharmacol 387:291-300. 2014
    ..1 function in vivo. However, distinct differences in K2P18.1 current regulation require careful consideration when zebrafish data are extrapolated to human physiology. ..
  62. doi Cloning, functional characterization, and remodeling of K2P3.1 (TASK-1) potassium channels in a porcine model of atrial fibrillation and heart failure
    Constanze Schmidt
    Department of Cardiology, University of Heidelberg, Heidelberg, Germany
    Heart Rhythm 11:1798-805. 2014
    ..In rodents, inhibition of K2P3.1 causes prolongation of action potentials and QT intervals. We used a porcine model to further elucidate the significance of K2P3.1 in large mammals...
  63. doi Enhancement of K2P2.1 (TREK1) background currents expressed in Xenopus oocytes by voltage-gated K+ channel β subunits
    Jana Kisselbach
    Department of Cardiology, University of Heidelberg, Heidelberg, Germany
    Life Sci 91:377-83. 2012
    ..Based on similar tissue distribution and common functional significance of Kvβ2 protein and K(2P)2.1 channels in neuronal excitability, we hypothesized that Kvβ2 subunits modulate K2P2.1 currents...
  64. doi cAMP sensitivity of HCN pacemaker channels determines basal heart rate but is not critical for autonomic rate control
    Patrick A Schweizer
    Department of Cardiology, Medical University Hospital Heidelberg, Heidelberg, Germany
    Circ Arrhythm Electrophysiol 3:542-52. 2010
    ..HCN4 represents the dominant isotype in the sinoatrial node and binding of cAMP was suggested to be necessary for autonomic heart rate regulation...
  65. doi Biophysical properties of mutant KCNQ1 S277L channels linked to hereditary long QT syndrome with phenotypic variability
    Parwez Aidery
    Department of Cardiology, Medical University Hospital Heidelberg, Im Neuenheimer Feld, Heidelberg, Germany
    Biochim Biophys Acta 1812:488-94. 2011
    ..The inconsistent association of the KCNQ1 S277L mutation with the clinical presentation suggests that additional genetic, epigenetic, or environmental factors play a role in defining the individual clinical LQTS phenotype...
  66. doi hERG K+ channel-associated cardiac effects of the antidepressant drug desipramine
    Ingo Staudacher
    Department of Cardiology, Medical University Hospital Heidelberg, Im Neuenheimer Feld 410, 69120, Heidelberg, Germany
    Naunyn Schmiedebergs Arch Pharmacol 383:119-39. 2011
    ..These data highlight the complexity of hERG-associated drug effects...
  67. pmc Doxazosin induces apoptosis of cells expressing hERG K+ channels
    Dierk Thomas
    Department of Cardiology, Medical University Hospital Heidelberg, Im Neuenheimer Feld 410, D 69120 Heidelberg, Germany
    Eur J Pharmacol 579:98-103. 2008
    ..An unexpected biological mechanism has emerged: binding of doxazosin to its novel membrane receptor, hERG, triggers apoptosis, possibly representing a broader pathophysiological mechanism in drug-induced heart failure...
  68. pmc Biological Heart Rate Reduction Through Genetic Suppression of Gα(s) Protein in the Sinoatrial Node
    Patrick Lugenbiel
    Department of Cardiology, Medical University Hospital Heidelberg, Germany
    J Am Heart Assoc 1:. 2012
    ..We hypothesized that genetic inactivation of the stimulatory Gα(s) protein in the sinoatrial node would provide sinus rate control and would prevent inappropriate heart rate acceleration during β-adrenergic activation...
  69. doi Atrioventricular delay programming in cardiac resynchronization therapy devices: fixed or adaptive? A randomized monocenter trial
    Melanie Schueler
    Department of Cardiology, University of Heidelberg, Heidelberg, Germany
    J Electrocardiol 45:783-6. 2012
    ..Whether this AVD also ensures optimal exercise hemodynamics, is unclear...
  70. ncbi Electrophysiological findings in Fabry cardiomyopathy: mapping the maze of risk stratification
    Jin Li
    Department of Cardiology, University of Heidelberg, Heidelberg, Germany
    Acta Cardiol 67:481-5. 2012
    ..Review of the literature indicates limited knowledge on the electrophysiology of Fabry cardiomyopathy and highlights the need for optimized risk stratification strategies...
  71. pmc Dronedarone: current evidence for its safety and efficacy in the management of atrial fibrillation
    Patrick A Schweizer
    Department of Cardiology, Medical University Hospital, Heidelberg, Germany
    Drug Des Devel Ther 5:27-39. 2011
    ....
  72. ncbi The novel antiarrhythmic drug dronedarone: comparison with amiodarone
    Sven Kathofer
    Department of Cardiology, Medical University Hospital Heidelberg, Im Neuenheimer Feld 410, D 69120 Heidelberg, Germany
    Cardiovasc Drug Rev 23:217-30. 2005
    ..However, further experimental studies and long-term clinical trials are required to provide additional evidence of efficacy and safety of dronedarone...
  73. ncbi hERG: protein trafficking and potential for therapy and drug side effects
    Ingo Staudacher
    Medical University Hospital Heidelberg, Department of Cardiology, Im Neuenheimer Feld 410, D 69120 Heidelberg, Germany
    Curr Opin Drug Discov Devel 13:23-30. 2010
    ....
  74. pmc The pathology and treatment of cardiac arrhythmias: focus on atrial fibrillation
    Constanze Schmidt
    Department of Cardiology, Medical University Hospital, Heidelberg, Germany
    Vasc Health Risk Manag 7:193-202. 2011
    ..Established drug therapy and interventional treatment of AF is reviewed, and emerging clinical and experimental therapeutic approaches are highlighted...
  75. doi Asymptomatic pulmonary vein stenosis after cryoballoon catheter ablation of paroxysmal atrial fibrillation
    Dierk Thomas
    Department of Cardiology, Medical University Hospital Heidelberg, Heidelberg, Germany
    J Electrocardiol 44:473-6. 2011
    ..Here, we report a case of asymptomatic PV stenosis associated with cryoballoon PV isolation, illustrating a risk that should be considered when applying this technique...
  76. pmc Alternative translation initiation in rat brain yields K2P2.1 potassium channels permeable to sodium
    Dierk Thomas
    Department of Pediatrics and Institute for Molecular Pediatric Sciences, Pritzker School of Medicine, University of Chicago, 5721 South Maryland Avenue, Chicago, IL 60637, USA
    Neuron 58:859-70. 2008
    ..Control of ion selectivity via ATI is proposed to be a natural, epigenetic mechanism for spatial and temporal regulation of neuronal excitability...