scholarly journals Non-ohmic tissue conduction in cardiac electrophysiology: Upscaling the non-linear voltage-dependent conductance of gap junctions

2020 ◽  
Vol 16 (2) ◽  
pp. e1007232 ◽  
Author(s):  
Daniel E. Hurtado ◽  
Javiera Jilberto ◽  
Grigory Panasenko
Keyword(s):  
Gap Junctions ◽  
Cardiac Electrophysiology ◽  
Non Linear ◽  
Voltage Dependent ◽  
Linear Voltage

Rectified and non-linear voltage-dependent membrane conductance of centrosymmetric oligoester bolaamphiphiles

2017 ◽  
Vol 30 (2) ◽  
pp. 146-157 ◽  
Author(s):  
Ye Zong ◽  
Thomas M. Fyles
Keyword(s):  
Membrane Conductance ◽  
Non Linear ◽  
Voltage Dependent ◽  
Linear Voltage

scholarly journals Non-ohmic tissue conduction in cardiac electrophysiology: upscaling the non-linear voltage-dependent conductance of gap junctions

2019 ◽  
Author(s):  
Daniel E. Hurtado ◽  
Javiera Jilberto ◽  
Grigory Panasenko
Keyword(s):  
Computational Complexity ◽  
Gap Junctions ◽  
Cardiac Tissue ◽  
Tissue Level ◽  
Cardiac Conduction ◽  
Non Linear ◽  
Voltage Dependent ◽  
Junctional Coupling ◽  
Organ Level ◽  
Electrical Propagation

AbstractGap junctions are key mediators of the intercellular communication in cardiac tissue, and their function is vital to sustain normal cardiac electrical activity. Conduction through gap junctions strongly depends on the hemichannel arrangement and transjunctional voltage, rendering the intercellular conductance highly non-Ohmic. Despite this marked non-linear behavior, current tissue-level models of cardiac conduction are rooted on the assumption that gap-junctions conductance is constant (Ohmic), which results in inaccurate predictions of electrical propagation, particularly in the low junctional-coupling regime observed under pathological conditions. In this work, we present a novel non-Ohmic multiscale (NOM) model of cardiac conduction that is suitable for tissue-level simulations. Using non-linear homogenization theory, we develop a conductivity model that seamlessly upscales the voltage-dependent conductance of gap junctions, without the need of explicitly modeling gap junctions. The NOM model allows for the simulation of electrical propagation in tissue-level cardiac domains that accurately resemble that of cell-based microscopic models for a wide range of junctional coupling scenarios, recovering key conduction features at a fraction of the computational complexity. A unique feature of the NOM model is the possibility of upscaling the response of non-symmetric gap-junction conductance distributions, which result in conduction velocities that strongly depend on the direction of propagation, thus allowing to model the normal and retrograde conduction observed in certain regions of the heart. We envision that the NOM model will enable organ-level simulations that are informed by sub- and inter-cellular mechanisms, delivering an accurate and predictive in-silico tool for understanding the heart function.Author summaryThe heart relies on the propagation of electrical impulses that are mediated gap junctions, whose conduction properties vary depending on the transjunctional voltage. Despite this non-linear feature, current mathematical models assume that cardiac tissue behaves like an Ohmic (linear) material, thus delivering inaccurate results when simulated in a computer. Here we present a novel mathematical multiscale model that explicitly includes the non-Ohmic response of gap junctions in its predictions. Our results show that the proposed model recovers important conduction features modulated by gap junctions at a fraction of the computational complexity. This contribution represents an important step towards constructing computer models of a whole heart that can predict organ-level behavior in reasonable computing times.

scholarly journals A non-linear voltage dependent charge movement in frog skeletal muscle.

1976 ◽  
Vol 254 (2) ◽  
pp. 245-283 ◽  
Author(s):  
W K Chandler ◽  
R F Rakowski ◽  
M F Schneider
Keyword(s):  
Skeletal Muscle ◽  
Charge Movement ◽  
Frog Skeletal Muscle ◽  
Non Linear ◽  
Voltage Dependent ◽  
Linear Voltage

scholarly journals A non-linear turn-off snubber for power electronic switches

1985 ◽  
Vol 4 (4) ◽  
pp. 143-146 ◽  
Author(s):  
C. G. Steyn ◽  
J. D. Van Wyk
Keyword(s):  
Power Device ◽  
Power Electronic ◽  
Electronic Switch ◽  
Stored Energy ◽  
Auxiliary Power ◽  
Non Linear ◽  
Voltage Dependent ◽  
Electronic Switches ◽  
Linear Voltage

A novel suggestion for a non-linear turn-off snubber is simulated experimentally with linear capacitors and an auxiliary power electronic switch. Thus the principle and advantages of this concept is partly illustrated, particularly concerning the important reduction of reactive stored energy for the same switching dissipation in the main power device. The full advantages of the concept will be realised when a snubber capacitor with non-linear, voltage dependent dielectric is used. The work on this part of the solution is being continued.

scholarly journals Proper Voltage-Dependent Ion Channel Function in Dysferlin-Deficient Cardiomyocytes

2015 ◽  
Vol 36 (3) ◽  
pp. 1049-1058 ◽  
Author(s):  
Lena Rubi ◽  
Vaibhavkumar S. Gawali ◽  
Helmut Kubista ◽  
Hannes Todt ◽  
Karlheinz Hilber ◽  
...  
Keyword(s):  
Ion Channels ◽  
Muscular Dystrophy ◽  
Ion Channel ◽  
Cardiac Electrophysiology ◽  
Cardiac Complications ◽  
Membrane Repair ◽  
Patch Clamp Technique ◽  
Cardiac Ion Channels ◽  
Ventricular Cardiomyocytes ◽  
Voltage Dependent

Background/Aims: Dysferlin plays a decisive role in calcium-dependent membrane repair in myocytes. Mutations in the encoding DYSF gene cause a number of myopathies, e.g. limb-girdle muscular dystrophy type 2B (LGMD2B). Besides skeletal muscle degenerative processes, dysferlin deficiency is also associated with cardiac complications. Thus, both LGMD2B patients and dysferlin-deficient mice develop a dilated cardiomyopathy. We and others have recently reported that dystrophin-deficient ventricular cardiomyocytes from mouse models of Duchenne muscular dystrophy show significant abnormalities in voltage-dependent ion channels, which may contribute to the pathophysiology in dystrophic cardiomyopathy. The aim of the present study was to investigate if dysferlin, like dystrophin, is a regulator of cardiac ion channels. Methods and Results: By using the whole cell patch-clamp technique, we compared the properties of voltage-dependent calcium and sodium channels, as well as action potentials in ventricular cardiomyocytes isolated from the hearts of normal and dysferlin-deficient (dysf) mice. In contrast to dystrophin deficiency, the lack of dysferlin did not impair the ion channel properties and left action potential parameters unaltered. In connection with normal ECGs in dysf mice these results suggest that dysferlin deficiency does not perturb cardiac electrophysiology. Conclusion: Our study demonstrates that dysferlin does not regulate cardiac voltage-dependent ion channels, and implies that abnormalities in cardiac ion channels are not a universal characteristic of all muscular dystrophy types.

scholarly journals Computational Approaches to Understanding the Role of Fibroblast-Myocyte Interactions in Cardiac Arrhythmogenesis

2015 ◽  
Vol 2015 ◽  
pp. 1-12 ◽  
Author(s):  
Tashalee R. Brown ◽  
Trine Krogh-Madsen ◽  
David J. Christini
Keyword(s):  
Gap Junctions ◽  
Potential Role ◽  
Cardiac Tissue ◽  
Cardiac Fibroblasts ◽  
Cardiac Arrhythmogenesis ◽  
Voltage Dependent ◽  
Underlying Mechanisms ◽  
Slow Propagation

The adult heart is composed of a dense network of cardiomyocytes surrounded by nonmyocytes, the most abundant of which are cardiac fibroblasts. Several cardiac diseases, such as myocardial infarction or dilated cardiomyopathy, are associated with an increased density of fibroblasts, that is, fibrosis. Fibroblasts play a significant role in the development of electrical and mechanical dysfunction of the heart; however the underlying mechanisms are only partially understood. One widely studied mechanism suggests that fibroblasts produce excess extracellular matrix, resulting in collagenous septa. These collagenous septa slow propagation, cause zig-zag conduction paths, and decouple cardiomyocytes resulting in a substrate for arrhythmia. Another emerging mechanism suggests that fibroblasts promote arrhythmogenesis through direct electrical interactions with cardiomyocytes via gap junctions. Due to the challenges of investigating fibroblast-myocyte coupling in native cardiac tissue, computational modeling andin vitroexperiments have facilitated the investigation into the mechanisms underlying fibroblast-mediated changes in cardiomyocyte action potential morphology, conduction velocity, spontaneous excitability, and vulnerability to reentry. In this paper, we summarize the major findings of the existing computational studies investigating the implications of fibroblast-myocyte interactions in the normal and diseased heart. We then present investigations from our group into the potential role of voltage-dependent gap junctions in fibroblast-myocyte interactions.

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