Cardiac Excitation and Repolarization

Keyword(s):  
Biomedicines ◽  
2021 ◽  
Vol 9 (7) ◽  
pp. 719
Author(s):  
Julia Hupfeld ◽  
Maximilian Ernst ◽  
Maria Knyrim ◽  
Stephanie Binas ◽  
Udo Kloeckner ◽  
...  

MicroRNAs (miRs) contribute to different aspects of cardiovascular pathology, among them cardiac hypertrophy and atrial fibrillation. Cardiac miR expression was analyzed in a mouse model with structural and electrical remodeling. Next-generation sequencing revealed that miR-208b-3p was ~25-fold upregulated. Therefore, the aim of our study was to evaluate the impact of miR-208b on cardiac protein expression. First, an undirected approach comparing whole RNA sequencing data to miR-walk 2.0 miR-208b 3′-UTR targets revealed 58 potential targets of miR-208b being regulated. We were able to show that miR-208b mimics bind to the 3′ untranslated region (UTR) of voltage-gated calcium channel subunit alpha1 C and Kcnj5, two predicted targets of miR-208b. Additionally, we demonstrated that miR-208b mimics reduce GIRK1/4 channel-dependent thallium ion flux in HL-1 cells. In a second undirected approach we performed mass spectrometry to identify the potential targets of miR-208b. We identified 40 potential targets by comparison to miR-walk 2.0 3′-UTR, 5′-UTR and CDS targets. Among those targets, Rock2 and Ran were upregulated in Western blots of HL-1 cells by miR-208b mimics. In summary, miR-208b targets the mRNAs of proteins involved in the generation of cardiac excitation and propagation, as well as of proteins involved in RNA translocation (Ran) and cardiac hypertrophic response (Rock2).


1990 ◽  
Vol 23 (1) ◽  
pp. 33-40 ◽  
Author(s):  
Shinji Watabe ◽  
Hiroshi Hayashi ◽  
Yoshiji Yamada ◽  
Kyoichi Miyaji ◽  
Seitaro Yabe ◽  
...  

2015 ◽  
Vol 773-774 ◽  
pp. 761-765
Author(s):  
Nur Atiqah Adon ◽  
Fahanahani Mahmud ◽  
Mohamad Hairol Jabbar ◽  
Norliza Othman

In past few decades, most of the modern electrophysiological concepts and methods were developed by the computational technique extensively to compute the cardiac action potential in nerve cells. Thus, tissue models consisting of a large number of single cell models cause a problem in the amount of computation required to obtain meaningful results from simulations. One of the solutions to this problem is by implementing the simulation through hardware modeling using a Field Programmable Gate Array (FPGA). Here, a research on developing a real-time simulation tool responsible for reentrant excitations in a ring of cardiac tissue based on the FitzHugh-Nagumo (FHN) model has been carried out by using a Xilinx Virtex-6 XC6VLX240T ML605 development board FPGA. In order to invest some of the time savings for creating the FPGA prototype, rapid prototyping method introduced by MathWorks which are MATLAB Simulink and its HDL Coder toolbox have been used to automate the algorithm design process by converting Simulink blocks into Hardware Description Language (HDL) code for the FPGA using a fixed-point data type in discrete-time framework. In this paper, the method and the optimization of the HDL design through the MATLAB Simulink have been discussed and the FPGA hardware performance in terms of speed, area and power consumption has also been analyzed.


2019 ◽  
Author(s):  
Nele Vandersickel ◽  
Enid Van Nieuwenhuyse ◽  
Nico Van Cleemput ◽  
Jan Goedgebeur ◽  
Milad El Haddad ◽  
...  

AbstractNetworks provide a powerful methodology with applications in a variety of biological, technological and social systems such as analysis of brain data, social networks, internet search engine algorithms, etc. To date, directed networks have not yet been applied to characterize the excitation of the human heart. In clinical practice, cardiac excitation is recorded by multiple discrete electrodes. During (normal) sinus rhythm or during cardiac arrhythmias, successive excitation connects neighboring electrodes, resulting in their own unique directed network. This in theory makes it a perfect fit for directed network analysis. In this study, we applied directed networks to the heart in order to describe and characterize cardiac arrhythmias. Proofof-principle was established using in-silico and clinical data. We demonstrated that tools used in network theory analysis allow to determine the mechanism and location of certain cardiac arrhythmias. We show that the robustness of this approach can potentially exceed the existing state-of-the art methodology used in clinics. Furthermore, implementation of these techniques in daily practice can improve accuracy and speed of cardiac arrhythmia analysis. It may also provide novel insights in arrhythmias that are still incompletely understood.


2018 ◽  
Vol 115 (3) ◽  
pp. 546-555 ◽  
Author(s):  
Zeynep Bastug-Özel ◽  
Peter T Wright ◽  
Axel E Kraft ◽  
Davor Pavlovic ◽  
Jacqueline Howie ◽  
...  

Abstract Aims Cyclic adenosine monophosphate (cAMP) regulates cardiac excitation–contraction coupling by acting in microdomains associated with sarcolemmal ion channels. However, local real time cAMP dynamics in such microdomains has not been visualized before. We sought to directly monitor cAMP in a microdomain formed around sodium–potassium ATPase (NKA) in healthy and failing cardiomyocytes and to better understand alterations of cAMP compartmentation in heart failure. Methods and results A novel Förster resonance energy transfer (FRET)-based biosensor termed phospholemman (PLM)-Epac1 was developed by fusing a highly sensitive cAMP sensor Epac1-camps to the C-terminus of PLM. Live cell imaging in PLM-Epac1 and Epac1-camps expressing adult rat ventricular myocytes revealed extensive regulation of NKA/PLM microdomain-associated cAMP levels by β2-adrenoceptors (β2-ARs). Local cAMP pools stimulated by these receptors were tightly controlled by phosphodiesterase (PDE) type 3. In chronic heart failure following myocardial infarction, dramatic reduction of the microdomain-specific β2-AR/cAMP signals and β2-AR dependent PLM phosphorylation was accompanied by a pronounced loss of local PDE3 and an increase in PDE2 effects. Conclusions NKA/PLM complex forms a distinct cAMP microdomain which is directly regulated by β2-ARs and is under predominant control by PDE3. In heart failure, local changes in PDE repertoire result in blunted β2-AR signalling to cAMP in the vicinity of PLM.


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