scholarly journals Computational analysis of the human sinus node action potential: model development and effects of mutations

2017 ◽  
Vol 595 (7) ◽  
pp. 2365-2396 ◽  
Author(s):  
Alan Fabbri ◽  
Matteo Fantini ◽  
Ronald Wilders ◽  
Stefano Severi
Keyword(s):  
Action Potential ◽  
Computational Analysis ◽  
Potential Model ◽  
Sinus Node ◽  
Model Development

scholarly journals Determinants of early afterdepolarization properties in ventricular myocyte models

2018 ◽  
Author(s):  
Xiaodong Huang ◽  
Zhen Song ◽  
Zhilin Qu
Keyword(s):  
Action Potential ◽  
Mathematical Models ◽  
Cardiac Myocytes ◽  
Potential Model ◽  
Model Development ◽  
Computer Models ◽  
Homoclinic Bifurcation ◽  
Early Afterdepolarizations ◽  
Potential Models ◽  
Repolarization Reserve

AbstractEarly afterdepolarizations (EADs) are spontaneous depolarizations during the repolarization phase of an action potential in cardiac myocytes. It is widely known that EADs are promoted by increasing inward currents and/or decreasing outward currents, a condition called reduced repolarization reserve. Recent studies based on bifurcation theories show that EADs are caused by a dual Hopf-homoclinic bifurcation, bringing in further mechanistic insights into the genesis and dynamics of EADs. In this study, we investigated the EAD properties, such as the EAD amplitude, the inter-EAD interval, and the latency of the first EAD, and their major determinants. We first made predictions based on the bifurcation theory and then validated them in physiologically more detailed action potential models. These properties were investigated by varying one parameter at a time or using parameter sets randomly drawn from assigned intervals. The theoretical and simulation results were compared with experimental data from the literature. Our major findings are that the EAD amplitude and takeoff potential exhibit a negative linear correlation; the inter-EAD interval is insensitive to the maximum ionic current conductance but mainly determined by the kinetics of ICa,L and the dual Hopf-homoclinic bifurcation; and both inter-EAD interval and latency vary largely from model to model. Most of the model results generally agree with experimental observations in isolated ventricular myocytes. However, a major discrepancy between modeling results and experimental observations is that the inter-EAD intervals observed in experiments are mainly between 200 and 500 ms, irrespective of species, while those of the mathematical models exhibit a much wider range with some models exhibiting inter-EAD intervals less than 100 ms. Our simulations show that the cause of this discrepancy is likely due to the difference in ICa,L recovery properties in different mathematical models, which needs to be addressed in future action potential model development.Author summaryEarly afterdepolarizations (EADs) are abnormal depolarizations during the plateau phase of action potential in cardiac myocytes, arising from a dual Hopf-homoclinic bifurcation. The same bifurcations are also responsible for certain types of bursting behaviors in other cell types, such as beta cells and neuronal cells. EADs are known to play important role in the genesis of lethal arrhythmias and have been widely studied in both experiments and computer models. However, a detailed comparison between the properties of EADs observed in experiments and those from mathematical models have not been carried out. In this study, we performed theoretical analyses and computer simulations of different ventricular action potential models as well as different species to investigate the properties of EADs and compared these properties to those observed in experiments. While the EAD properties in the action potential models capture many of the EAD properties seen in experiments, the inter-EAD intervals in the computer models differ a lot from model to model, and some of them show very large discrepancy with those observed in experiments. This discrepancy needs to be addressed in future cardiac action potential model development.

scholarly journals Percolation and tortuosity in heart-like cells

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
R. Rabinovitch ◽  
Y. Biton ◽  
D. Braunstein ◽  
I. Aviram ◽  
R. Thieberger ◽  
...  
Keyword(s):  
Action Potential ◽  
Forest Fire ◽  
Sinus Node ◽  
Heart Tissue ◽  
Point Of View ◽  
Physical Point ◽  
Electrical Currents ◽  
Single Wave ◽  
Heart Arrhythmia ◽  
The One

AbstractIn the last several years, quite a few papers on the joint question of transport, tortuosity and percolation have appeared in the literature, dealing with passage of miscellaneous liquids or electrical currents in different media. However, these methods have not been applied to the passage of action potential in heart fibrosis (HF), which is crucial for problems of heart arrhythmia, especially of atrial tachycardia and fibrillation. In this work we address the HF problem from these aspects. A cellular automaton model is used to analyze percolation and transport of a distributed-fibrosis inflicted heart-like tissue. Although based on a rather simple mathematical model, it leads to several important outcomes: (1) It is shown that, for a single wave front (as the one emanated by the heart's sinus node), the percolation of heart-like matrices is exactly similar to the forest fire case. (2) It is shown that, on the average, the shape of the transport (a question not dealt with in relation to forest fire, and deals with the delay of action potential when passing a fibrotic tissue) behaves like a Gaussian. (3) Moreover, it is shown that close to the percolation threshold the parameters of this Gaussian behave in a critical way. From the physical point of view, these three results are an important contribution to the general percolation investigation. The relevance of our results to cardiological issues, specifically to the question of reentry initiation, are discussed and it is shown that: (A) Without an ectopic source and under a mere sinus node operation, no arrhythmia is generated, and (B) A sufficiently high refractory period could prevent some reentry mechanisms, even in partially fibrotic heart tissue.

Electrophysiological heterogeneity and stability of reentry in simulated cardiac tissue

2001 ◽  
Vol 280 (2) ◽  
pp. H535-H545 ◽  
Author(s):  
Fagen Xie ◽  
Zhilin Qu ◽  
Alan Garfinkel ◽  
James N. Weiss
Keyword(s):  
Action Potential ◽  
Action Potential Duration ◽  
Cardiac Tissue ◽  
Potential Model ◽  
Dynamic Instability ◽  
Spatial Scales ◽  
Cardiac Cells ◽  
Dynamic Factors ◽  
Cardiac Model ◽  
Wave Break

Generation of wave break is a characteristic feature of cardiac fibrillation. In this study, we investigated how dynamic factors and fixed electrophysiological heterogeneity interact to promote wave break in simulated two-dimensional cardiac tissue, by using the Luo-Rudy (LR1) ventricular action potential model. The degree of dynamic instability of the action potential model was controlled by varying the maximal amplitude of the slow inward Ca2+ current to produce spiral waves in homogeneous tissue that were either nearly stable, meandering, hypermeandering, or in breakup regimes. Fixed electrophysiological heterogeneity was modeled by randomly varying action potential duration over different spatial scales to create dispersion of refractoriness. We found that the degree of dispersion of refractoriness required to induce wave break decreased markedly as dynamic instability of the cardiac model increased. These findings suggest that reducing the dynamic instability of cardiac cells by interventions, such as decreasing the steepness of action potential duration restitution, may still have merit as an antifibrillatory strategy.

scholarly journals Theoretical Aspects of Resting-State Cardiomyocyte Communication for Multi-Nodal Nano-Actuator Pacemakers

Sensors ◽  
2020 ◽  
Vol 20 (10) ◽  
pp. 2792
Author(s):  
Pengfei Lu ◽  
Mladen Veletić ◽  
Jacob Bergsland ◽  
Ilangko Balasingham
Keyword(s):  
Action Potential ◽  
Resting State ◽  
Communication Channel ◽  
Potential Model ◽  
Signal Propagation ◽  
Cardiac Cells ◽  
The Body ◽  
Cardiac Muscle Cells ◽  
Leadless Pacemaker ◽  
Communication Technique

The heart consists of billions of cardiac muscle cells—cardiomyocytes—that work in a coordinated fashion to supply oxygen and nutrients to the body. Inter-connected specialized cardiomyocytes form signaling channels through which the electrical signals are propagated throughout the heart, controlling the heart’s beat to beat function of the other cardiac cells. In this paper, we study to what extent it is possible to use ordinary cardiomyocytes as communication channels between components of a recently proposed multi-nodal leadless pacemaker, to transmit data encoded in subthreshold membrane potentials. We analyze signal propagation in the cardiac infrastructure considering noise in the communication channel by performing numerical simulations based on the Luo-Rudy computational model. The Luo-Rudy model is an action potential model but describes the potential changes with time including membrane potential and action potential stages, separated by the thresholding mechanism. Demonstrating system performance, we show that cardiomyocytes can be used to establish an artificial communication system where data are reliably transmitted between 10 s of cells. The proposed subthreshold cardiac communication lays the foundation for a new intra-cardiac communication technique.

1107 Analysis of relation between QT interval and KCNE1/KCNQ1 expression ratio by using cardiac membrane action potential model

2007 ◽  
Vol 2007.5 (0) ◽  
pp. 281-282
Author(s):  
Takahiro YAMAGUCHI ◽  
Ichiro SAKUMA ◽  
Nitaro SHIBATA ◽  
Haruo HONJO ◽  
Itsuo KODAMA ◽  
...  
Keyword(s):  
Action Potential ◽  
Qt Interval ◽  
Potential Model ◽  
Membrane Action ◽  
Expression Ratio ◽  
Cardiac Membrane

Dynamics of drug binding to the hERG channel: An in silico cardiac action potential model for early safety assessment

2012 ◽  
Vol 66 (2) ◽  
pp. 171
Author(s):  
Giovanni Y. Di Veroli ◽  
Mark Davies ◽  
Chris E. Pollard ◽  
Jean-Pierre Valentin ◽  
Henggui Zhang ◽  
...  
Keyword(s):  
Action Potential ◽  
In Silico ◽  
Safety Assessment ◽  
Potential Model ◽  
Drug Binding ◽  
Herg Channel ◽  
Cardiac Action Potential ◽  
Cardiac Action
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