Kliniken & Institute … Kliniken Zentrum für Innere… Internal Medicine III:… Research Arbeitsgruppen Klinische Forschung und… Task force for ion…

Research

Aims

 

The understanding of the pathophysiological mechanisms of arrhythmogenesis in ion channel cardiomyopathies still remains a key scientific challenge. Over the last years, substantial progress has been made in the dissection of the molecular structure-function relationship of cardiac ion channel mutations. Functional relevance of these changes has been further issued in animal models. However, whereas these experiments allow deep insights into disease mechanisms on a molecular and cellular level, the influence on arrhythmogenesis in humans can only be hardly predicted.
Using an integrative approach of clinical phenotyping and genotyping in combination with molecular structure-function analyses, in vivo characterization, and bioinformatics, we established a multilevel translational approach to analyze the pathogenetic link between genotype and clinical phenotype.

For this purpose, close collaboration with scientific partners on campus (Zebrafish Unit, Interdisciplinary Center for Scientific Computing) as well as remote partners (KIT, Karlsruhe) has been established.
This combination of molecular electrophysiology with mathematical modeling allows exceptional insights into the mechanisms of electrophysiological processes. Furthermore this approach provides a unique possibility to assess antiarrhythmic properties of novel therapies.

 

Simulation of excitation propagation within the cardiac conduction system

Within a cooperative project with the center for scientific calculating the working group develops novel mathematical models describing the excitation propagation in the cardiac conduction system. The goal is to get a better understanding of the involved processes.

 

 

Cooperation partner:

Dr. Sebastian Sager (Interdisciplinary Center for Scientific Computing, University of Heidelberg)

 

Selected Publications

  1. Scholz EP, Welke F, Seyler C, Völker M, Bloehs R, Thomas D, Kathöfer S, Katus HA, Karle C, Zitron E. Central role of PKCalpha in isoenzyme-selective regulation of cardiac transient outward current Ito and Kv4.3 channels. J Mol Cell Cardiol 2011, 51(5):722-9.
  2. Meder B, Scholz EP (gleichberechtigter Erstautor), Hassel D, Wolff C, Just S, Berger IM, Patzel E, Karle C, Katus HA, Rottbauer W.: Reconstitution of Defective Protein Trafficking Rescues Long-QT Syndrome in Zebrafish. Biochem Biophys Res Comm 2011, 408(2):218-24.
  3. Scholz EP, Zitron E, Katus HA, Karle C: Cardiovascular ion channels as molecular targets of flavonoids. Cardiovascular Therapeutics 2010, 28(4):e46-52.
  4. Scholz EP, Niemer N, Hassel D, Zitron E, Bürgers HF, Bloehs R, Seyler C, Scherer D, Thomas D, Kathöfer S, Katus HA, Rottbauer WA, Karle CA.: Biophysical properties of zebrafish ether-à-go-go related gene potassium channels. Biochem Biophys Res Comm 2009, 381(2):159-64.
  5. Scherer D, Hassel D, Bloehs R, Zitron E, von Löwenstern K, Seyler C, Thomas D, Konrad F, Bürgers HF, Seemann G, Rottbauer W, Katus HA, Karle CA, Scholz EP. Selective noradrenaline reuptake inhibitor atomoxetine directly blocks hERG currents. Br J Pharmacol. 2009, 156(2):226-36.
  6. Hassel D*, Scholz EP* (*gleichberechtigter Erstautor), Trano N, Friedrich O, Just S, Meder B, Weiss DL, Zitron E, Marquart S, Vogel B, Karle CA, Seemann G, Fishman MC, Katus HA, Rottbauer W: Deficient Zebrafish Ether-a-Go-Go-Related Gene Channel Gating Causes Short-QT Syndrome in Zebrafish Reggae Mutants. Circulation 2008, 19;117(7):866-75.
  7. Seemann G, Carillo P, Weiss DL, Krueger MW, Dössel O, Scholz EP: Investigating Arrhythmogenic Effects of the hERG Mutation N588K in Virtual Human Atria. Lecture Notes in Computer Science 2008, 5528:144-153.
  8. Scholz EP, Konrad FM, Weiss DL, Zitron E, Kiesecker C, Bloehs R, Kulzer M, Thomas D, Kathöfer S, Bauer A, Maurer MH, Seemann G, Katus HA, Karle CA: Anticholinergic antiparkinson drug orphenadrine inhibits HERG channels: block attenuation by mutations of the pore residues Y652 or F656. Naunyn Schmiedebergs Arch Pharmacol 2007, 376:275-284.
  9. Scholz EP, Zitron E, Kiesecker C, Thomas D, Kathöfer S, Kreuzer J, Bauer A, Katus HA, Remppis A, Karle CA, Greten J: Orange flavonoid hesperetin modulates cardiac hERG potassium channel via binding to amino acid F656. Nutr Metab Cardiovasc Dis 2007, 17:666-675.
  10. Scholz EP, Alter M, Zitron E, Kiesecker C, Kathöfer S, Thomas D, Kreye VAW, Kreuzer J, Becker R, Katus HA, Greten J, Karle CA: In vitro modulation of HERG channels by organochlorine solvent trichlormethane as potential explanation for proarrhythmic effects of chloroform. Toxicol Lett 2006, 165:156-166.
  11. Zitron E*, Scholz E* (*gleichberechtigter Erstautor), Owen RW, Lück S, Kiesecker C, Thomas D, Kathöfer S, Niroomand F, Kiehn J, Kreye VAW, Katus HA, Schoels W, Karle CA: QTc prolongation by grapefruit juice and its potential pharmacological basis: HERG channel blockade by flavonoids. Circulation 2005, 111:835-838.
  12. Scholz EP, Zitron E, Kiesecker C, Lück S, Thomas D, Kathöfer S, Kreye VAW, Katus HA, Kiehn J, Schoels W, Karle CA: Inhibition of cardiac HERG channels by grapefruit flavonoid naringenin: implications for the influence of dietary compounds on cardiac repolarisation. Naunyn Schmiedebergs Arch Pharmacol 2005, 371:516-525.
  13. Scholz EP, Zitron E, Kiesecker C, Lueck S, Kathöfer S, Thomas D, Weretka S, Peth S, Kreye VAW, Schoels W, Katus HA, Kiehn J, Karle CA: Drug binding to aromatic residues in the HERG channel pore cavity as possible explanation for acquired Long QT syndrome by antiparkinsonian drug budipine. Naunyn Schmiedebergs Arch Pharmacol 2003, 368:404-414.

Reserach Funding

Two projects are currently funded by grants from the German Research Foundationeutsche Forschungsgemeinschaft (DFG)

 

Vacancies

At present there are no job vacancies.