Faculty of Medicine Masaryk University

 

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Tibor Stračina
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Working Group Cardiac Electrophysiology

Actualities

In 2016, we offer 3 available PhD positions with the following topics. For more information, please contact Assoc. Prof. Markéta Bébarová (mbebar@med.muni.cz).

Topic I: Changes of ionic channel properties caused by mutations associated with inherited arrhythmias
Annotation:
Inherited arrhythmias (for example the long QT syndrome) are rare, life-threatening diseases caused by mutations in cardiac ionic channels. Study of the identified mutations considerably helps to understand arrhythmogenic mechanisms and, importantly, to consider prognosis of the disorder in mutation carriers. It is crucial because the syndrome may be manifested by a fatal arrhythmia for the first time, even in young age. The goal of this study will be to find out functional differences between wild type channels and channels encompassing selected mutation identified in a concrete patient (whole cell patch clamp technique in human wild-type and mutant ionic channels expressed in a cell line). The study results should ideally lead to a prospective explanation of the arrhythmogenesis and to an estimation of the risk resulting from the mutation carriage.

Topic II: Drug-induced changes of cardiac inward rectifier currents and their impact on cardiac electrophysiology
Annotation:
Cardiac inward rectifier currents play an essential role in stabilization of the resting membrane potential and contribute to the final phase of cardiac repolarization. Considerable modifications of these currents were observed in some cardiac pathologies, namely in the atrial fibrillation (AF) and also in the life-threatening ventricular fibrillation (VF). Pharmacological agents inducing similar changes of cardiac inward rectifier currents might provoke clinical manifestation of the pathology, or contribute to its worsening. As known, the drug-induced AF and VF are related to many drugs used in clinical practise. This project will be focused on analysis of effects of several drugs suspicious from AF and/or VF provocation on cardiac inward rectifier currents (whole cell patch clamp technique in isolated cardiomyocytes).

Topic III: Computational modelling of electromechanical activity of cardiomyocytes in failing hearts
Annotation:
Heart failure is characterized by an impairment of the cardiac muscle with decreased cardiac output in spite of sufficient filling of the heart. Ischemic symptoms from various tissues appear. To effectively treat patients with these symptoms in clinical practise, it is crucial to understand cellular and molecular mechanisms underlying this pathological state. The aim of this work is to mathematically formulate the changes in membrane ion transport and in the excitation - contraction coupling of failing hearts, and to explore the consequences of these changes for the electromechanical activity of cardiomyocytes by means of computational modelling.

About the group

The research group of Cellular Electrophysiology originates from the fruitful history of electrophysiological experiments on the multicellular level which were performed at the Department of Physiology FM MU from 1960s.

Within the last 10 years, our research activities are focused namely on analyses of effects of various drugs used in the clinical medicine (e.g. the antiarrhythmic drug ajmaline and the antipsychotic drug perphenazine) and also of addictive drugs (ethanol and nicotine) on ionic membrane currents and action potential configuration of both ventricular and atrial cardiac cells enzymatically isolated from hearts of small laboratory animals. In parallel, we also deal with mathematical simulations of electrophysiological events in cardiomyocytes and of drug effects.

Within the scope of study of functional impact of t-tubules in cardiac cells, we have newly focused on the analysis of capacity of t-tubular membrane, and rate of ion diffusion between t-tubules and extracellular space. This information is essential for improvement of our mathematical models of cardiac cells that we use both in analysis of the impact of t-tubules in cardiac cells and in modelling of the drug effects (see above).

In recent years, we have introduced measurement of ionic currents through human ionic channels transiently expressed in a cell line. This method enables to deal with a completely new research area, for example to analyse the functional impact of ionic channel mutations associated with inherited arrhythmias (e.g. long QT syndrome, Brugada syndrome) or with other monogenic inherited diseases.

Areas of focus:

  • Effect of pharmacological agents on electrophysiological properties of cardiac cells – changes of ionic currents and action potential configuration
  • Functional impact of t-tubules in cardiac cells, capacity of t-tubular system, rate of ion diffusion between t-tubules and extracellular space
  • Functional impact of ionic channel mutations associated with inherited arrhythmias (e.g. long QT syndrome, Brugada syndrome)

People

Coordinator Assoc. Prof. MUDr. Markéta Bébarová, Ph.D.
 
Researchers Assoc. Prof. Ing. Michal Pásek, Ph.D.
Assoc. Prof. MUDr. Milena Šimurdová, CSc.
Assoc. Prof. RNDr. Ing. Jiří Šimurda, CSc.
Ing. Olga Švecová, Ph.D.
 
Undergraduate students Roman Kula (3. roč. LF MU; P-PooL)
Martin Macháček (3. roč. LF MU; P-PooL)
Akimasa Iijima (2. roč. LF MU; SVOČ)
Nuno Jorge Dourado Ramalho (3. roč. LF MU; SVOČ)
Ivana Tomaškovicová (4. roč. LF MU; student project)
Dominik Fabián (3. roč. LF MU; student project)
Bc. Júlia Šatková (Faculty of Science MU, field of study: Medical Genetics and Molecular Diagnostics; diploma thesis)
Bc. Marcela Policarová (Faculty of Science MU, field of study: Medical Genetics and Molecular Diagnostics; diploma thesis)
Bc. Barbora Skupníková (Faculty of Science MU, field of study: Medical Genetics and Molecular Diagnostics; diploma thesis)
 
Technicians Branislava Vyoralová
 

Established Methods and Experimental Models

  • whole cell patch clamp measurement on ventricular (B) and atrial (C) cardiac cells freshly enzymatically isolated from hearts of small laboratory animals perfused according to Langendorff (A)
  • whole cell patch clamp measurement on isolated cardiac cells following their short-term incubation
  • whole cell patch clamp measurement on a cell line transiently expressing human ionic channels (D)
  • whole cell patch clamp measurement on mouse cardiomyocytes differentiated from pluripotent stem cells
  • mathematical modelling (E) – to simulate cellular events, we actually have human, rat and guinea-pig ventricular cell models published in prestigious journals include are:; human and rat atrial cell models are in preparation

Cellular Electrophysiology

Research Grants

  • 2016-2019: Clinical signifikance and electrophysiological evaluation of KCNQ1 gene mutation c.926CT (p.T309I) as a possible long QT syndrome founder mutation (16-30571A; investor: AZV MZ ČR; co-investigator: Assoc. Prof. M. Bébarová)
  • 2018: Kardiovaskulární systém napříč obory – od molekulární diagnostiky po klinická vyšetření (MUNI/A/1157/2017; investor: MU - specific research project; principal investigator: prof. M. Nováková)
  • 2016: Kardiovaskulární systém: od modelu přes terapii k prevenci („Cardiovascular system: from model through therapy to prevention“; MUNI/A/1365/2015; investor: MU – specific research project; principal investigator: Prof. M. Nováková)
  • 2015: Kardiovaskulární systém od buňky k lůžku pacienta („Cardiovascular system from cell to bedsight“; MUNI/A/1326/2014; investor: MU - specific research project; principal investigator: Prof. M. Nováková)
  • 2013 – 2015: Effect of ethanol and its principle metabolite acetaldehyde on cardiac inward rectifier potassium currents: a link to atrial fibrillation related to alcohol consumption? (NT14301-3/2013; investor: IGA of the Ministry of Health of the CR; principal investigator: Assoc. Prof. M. Bébarová)
  • 2003: Effects of ajmaline on membrane currents in cardiomyocytes (FRVS/492/2003; investor: University Development Fund of the Ministry of Education, Youth and Sports of the CR; principal investigator: Assoc. Prof. M. Bébarová)
  • 2002 – 2004: Quantitative analysis of effect of tubular system on electrical activity of cardiac cells (GP204/02/D129; investor: Czech Science Foundation; principal investigator: Assoc. Prof. M. Pásek)

Co-operations

  • Dr. Georges Christé (Inserm, Lyon, France)
  • prof. Paul G.A. Volders (Maastricht University, Maastricht, Netherlands)
  • RNDr. Jan Hošek, Ph.D. (University of Veterinary and Pharmaceutical Sciences Brno)
  • doc. MUDr. Tomáš Novotný, Ph.D. (Department of Internal Cardiology Medicine, FN Brno)
  • prim. MUDr. Renata Gaillyová, Ph.D. (Department of Medical Genetics, FN Brno)
  • Mgr. Jiří Pacherník, Ph.D. (Department of Experimental Biology, Faculty of Science MU)
  • Ing. Vratislav Čmiel, Ph.D. (Department of Biomedical Engineering, VUT Brno)
  • Mgr. Josef Skopalík, Ph.D. (Department of Biomedical Engineering, VUT Brno)
  • Larisa Baiazitova (Department of Biomedical Engineering, VUT Brno)
Selected Recent Papers
  • Šimurda J, Šimurdová M, Bébarová M. Inward rectifying potassium currents resolved into components: modeling of complex drug actions. Pflugers Arch 2018;470(2):315-325.
  • Bébarová M, Matejovič P, Švecová O, Kula R, Šimurdová M, Šimurda J. Nicotine at clinically relevant concentrations affects atrial inward rectifier potassium current sensitive to acetylcholine. Naunyn Schmiedeberg´s Arch Pharmacol 2017;390(5):471-481.
  • Radaszkiewicz KA, Sýkorová D, Binó L, Kudová J, Bébarová M, Procházková J, Kotasová H, Kubala L, Pacherník J. The acceleration of cardiomyogenesis in embryonic stem cells in vitro by serum depletion does not increase the number of developed cardiomyocytes. PLoS One 2017;12(3):e0173140.
  • Pásek M, Šimurda J, Christé G. Different Densities of Na-Ca Exchange Current in T-Tubular and Surface Membranes and Their Impact on Cellular Activity in a Model of Rat Ventricular Cardiomyocyte. Biomed Res Int 2017;2017:6343821.
  • Bébarová M, Hořáková Z, Kula R. Addictive drugs, arrhythmias and cardiac inward rectifiers. Europace 2017;19(3):346-355.
  • Bébarová M, Matejovič P, Pásek M, Hořáková Z, Hošek J, Šimurdová M, Šimurda J. Effect of ethanol at clinically relevant concentrations on atrial inward rectifier potassium current sensitive to acetylcholine. Naunyn Schmiedeberg´s Arch Pharmacol 2016;389:1049-1058
  • Pásek M, Bébarová M, Christé G, Šimurdová M, Šimurda J. Acute effects of ethanol on action potential and intracellular Ca2+ transient in cardiac ventricular cells: a simulation study. Med Biol Eng Comput 2016;54:753-762.
  • Bébarová M, Matejovič P, Pásek M, Šimurdová M, Šimurda J. Dual effect of ethanol on inward rectifier potassium current IK1 in rat ventricular myocytes. J Physiol Pharmacol 2014;6:497-509.
  • Pásek M, Šimurda J, Orchard CH. Effect of Ca2+ efflux pathway distribution and exogenous Ca2+ buffers on intracellular Ca2+ dynamics in the rat ventricular myocyte: a simulation study. Biomed Res Int 2014;2014:920208.
  • Hrabcová D, Pásek M, Šimurda J, Christé G. Effect of ion concentration changes in the limited extracellular spaces on sarcolemmal ion transport and Ca2+ turnover in a model of human ventricular cardiomyocyte. Int J Mol Sci 2013;14:24271-24292.
 

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