scholarly journals The Mechanisms of Calcium Cycling and Action Potential Dynamics in Cardiac Alternans

2015 ◽  
Vol 116 (5) ◽  
pp. 846-856 ◽  
Author(s):  
Giedrius Kanaporis ◽  
Lothar A. Blatter
Keyword(s):  
Action Potential ◽  
Calcium Cycling ◽  
Cardiac Alternans

scholarly journals Role of Oxidation-Dependent CaMKII Activation in the Genesis of Abnormal Action Potentials in Atrial Cardiomyocytes: A Simulation Study

2020 ◽  
Vol 2020 ◽  
pp. 1-13
Author(s):  
Na Zhao ◽  
Qince Li ◽  
Haibo Sui ◽  
Henggui Zhang
Keyword(s):  
Oxidative Stress ◽  
Action Potential ◽  
Intracellular Calcium ◽  
Action Potentials ◽  
Cell Model ◽  
Atrial Arrhythmia ◽  
Electrical Excitation ◽  
Calcium Cycling ◽  
Simulation Results ◽  
Camkii Activation

Atrial fibrillation is a common cardiac arrhythmia with an increasing incidence rate. Particularly for the aging population, understanding the underlying mechanisms of atrial arrhythmia is important in designing clinical treatment. Recently, experiments have shown that atrial arrhythmia is associated with oxidative stress. In this study, an atrial cell model including oxidative-dependent Ca2+/calmodulin- (CaM-) dependent protein kinase II (CaMKII) activation was developed to explore the intrinsic mechanisms of atrial arrhythmia induced by oxidative stress. The simulation results showed that oxidative stress caused early afterdepolarizations (EADs) of action potentials by altering the dynamics of transmembrane currents and intracellular calcium cycling. Oxidative stress gradually elevated the concentration of calcium ions in the cytoplasm by enhancing the L-type Ca2+ current and sarcoplasmic reticulum (SR) calcium release. Owing to increased intracellular calcium concentration, the inward Na+/Ca2+ exchange current was elevated which slowed down the repolarization of the action potential. Thus, the action potential was prolonged and the L-type Ca2+ current was reactivated, resulting in the genesis of EAD. Furthermore, based on the atrial single-cell model, a two-dimensional (2D) ideal tissue model was developed to explore the effect of oxidative stress on the electrical excitation wave conduction in 2D tissue. Simulation results demonstrated that, under oxidative stress conditions, EAD hindered the conduction of electrical excitation and caused an unstable spiral wave, which could disrupt normal cardiac rhythm and cause atrial arrhythmia. This study showed the effects of excess reactive oxygen species on calcium cycling and action potential in atrial myocytes and provided insights regarding atrial arrhythmia induced by oxidative stress.

Cardiac Alternans Arising From an Unfolded Border-Collision Bifurcation

2007 ◽  
Author(s):  
Xiaopeng Zhao ◽  
David G. Schaeffer ◽  
Carolyn M. Berger ◽  
Wanda Krassowska ◽  
Daniel J. Gauthier
Keyword(s):  
Action Potential ◽  
Cardiac Tissue ◽  
Medical Literature ◽  
Period Doubling ◽  
Electrical Stimulus ◽  
Period Doubling Bifurcation ◽  
Small Interval ◽  
Border Collision Bifurcation ◽  
Transmembrane Voltage ◽  
Cardiac Alternans

Following an electrical stimulus, the transmembrane voltage of cardiac tissue rises rapidly and remains at a constant value before returning to the resting value, a phenomenon known as an action potential. When the pacing rate of a periodic train of stimuli is increased above a critical value, the action potential undergoes a period-doubling bifurcation, where the resulting alternation of the action potential duration is known as alternans in the medical literature. In principle, a period-doubling bifurcation may occur through either a smooth or a nonsmooth mechanism. Previous experiments reveal that the bifurcation to alternans exhibits hybrid smooth/nonsmooth behaviors, which is due to large variations in the system’s properties over a small interval of bifurcation parameter. To reproduce the experimentally observed hybrid behaviors, we have developed a model of alternans that exhibits an unfolded border-collision bifurcation. Excellent agreement between simulation of the model and experimental data suggests that features of the unfolded border-collision model should be included in modeling cardiac alternans.

Bifurcation of Spatiotemporal Cardiac Alternans

2008 ◽  
Author(s):  
Xiaopeng Zhao
Keyword(s):  
Action Potential ◽  
Cardiac Tissue ◽  
Period Doubling ◽  
Heart Rhythm ◽  
The Us ◽  
Coupled Cells ◽  
Cardiac Alternans ◽  
Rhythm Disorder ◽  
Bifurcation Structures ◽  
And Control

Cardiac alternans is an initiator of ventricular fibrillation, a fatal heart rhythm disorder that kills hundreds of thousands people in the US each year. Alternans manifests as a pattern with beat-to-beat long-short variations in action potential duration. In an isolated cardiac cell, alternans arises as a supercritical period-doubling bifurcation. In cardiac tissue (coupled cells), propagation effect leads to more complicated bifurcation structures. Specifically, there may coexist multiple spatiotemporal patterns of alternans in tissue due to the interaction between electrotonic coupling and intrinsic instability in the dynamics of action potential. In this work, we carry out a detailed bifurcation analysis to illustrate the mechanism that leads to this phenomenon. The results on this analysis may shed light on the onset and control of the dreadful instability of cardiac alternans.

scholarly journals Cardiac alternans induced by fibroblast-myocyte coupling: mechanistic insights from computational models

2009 ◽  
Vol 297 (2) ◽  
pp. H775-H784 ◽  
Author(s):  
Yuanfang Xie ◽  
Alan Garfinkel ◽  
James N. Weiss ◽  
Zhilin Qu
Keyword(s):  
Action Potential ◽  
Computational Models ◽  
Cardiac Tissue ◽  
Experimental Studies ◽  
Outward Current ◽  
Transient Outward Current ◽  
Two Dimensional ◽  
Background Current ◽  
Cardiac Alternans ◽  
Main Components

Recent experimental studies have shown that fibroblasts can electrotonically couple to myocytes via gap junctions. In this study, we investigated how this coupling affects action potential and intracellular calcium (Cai) cycling dynamics in simulated fibroblast-myocyte pairs and in two-dimensional tissue with random fibroblast insertions. We show that a fibroblast coupled with a myocyte generates a gap junction current flowing to the myocyte with two main components: an early pulse of transient outward current, similar to the fast transient outward current, and a later background current during the repolarizing phase. Depending on the relative prominence of the two components, fibroblast-myoycte coupling can 1) prolong or shorten action potential duration (APD), 2) promote or suppress APD alternans due to steep APD restitution (voltage driven) and also result in a novel mechanism of APD alternans at slow heart rates, 3) promote Cai-driven alternans and electromechanically discordant alternans, and 4) promote spatially discordant alternans by two mechanisms: by altering conduction velocity restitution and by heterogeneous fibroblast distribution causing electromechanically concordant and discordant alternans in different regions of the tissue. Thus, through their coupling with myocytes, fibroblasts alter repolarization and Cai cycling alternans at both the cellular and tissue scales, which may play important roles in arrhythmogenesis in diseased cardiac tissue with fibrosis.

Hypothermia-induced spatially discordant action potential duration alternans and arrhythmogenesis in nonhibernating versus hibernating mammals

2012 ◽  
Vol 303 (8) ◽  
pp. H1035-H1046 ◽  
Author(s):  
Yuriy V. Egorov ◽  
Alexey V. Glukhov ◽  
Igor R. Efimov ◽  
Leonid V. Rosenshtraukh
Keyword(s):  
Action Potential ◽  
Action Potential Duration ◽  
Conduction Block ◽  
Ground Squirrels ◽  
Dispersion Of Repolarization ◽  
Epicardial Surface ◽  
Cardiac Alternans ◽  
Spermophilus Undulatus ◽  
Perfused Hearts ◽  
Low Dispersion

The heart of hibernating species is resistant to lethal ventricular fibrillation (VF) induced by hypothermia. Spatially discordant (SDA) cardiac alternans is a promising predictor of VF, yet its role in the mechanism of hypothermic arrhythmogenesis in both nonhibernating and hibernating mammals remains unclear. We optically mapped the posterior epicardial surface of Langendorff-perfused hearts of winter hibernating (WH, n = 13), interbout arousal (IBA; n = 4), and summer active (SA, n = 6) ground squirrels (GSs; Spermophilus undulatus) and rabbits ( n = 10). Action potential duration (APD) and conduction velocity (CV) dynamic restitution and alternans were determined at 37 to 17°C. In all animals, hypothermia induced heterogeneous APD prolongation, enhanced APD dispersion, and slowed CV. In all groups, hypothermia promoted the formation of APD alternans, which was predominantly spatially concordant in GSs and SDA in rabbits (SD of APD dispersion: 4.2 ± 0.4% vs. 2.0 ± 0.3% at 37°C and 7.5 ± 1.1% vs. 3.4 ± 0.5% at 17°C, P < 0.001 for rabbits vs. the WH group, respectively). In rabbits, hypothermia significantly increased the magnitude of SDA, which enhanced the ventricular repolarization gradient, caused conduction delays (CV: 3.2 vs. 8.2 cm/s at 17°C in rabbits vs. the WH group), conduction block, and the onset of VF (0% at 37°C vs. 60% at 17°C, P < 0.01). In contrast, no arrhythmia was observed in GS hearts at any temperature. The amplitude of CV alternans was greater in rabbits (5.2 ± 0.4% versus 4.5 ± 0.3% at 37°C and 35.3 ± 4.2% vs. 14.9 ± 1.5% at 17°C in rabbits vs. the WH group, P < 0.001 at 17°C) and correlated with the amplitude of SDA. In conclusion, the mechanism underlying SDA formation during hypothermia is likely associated with CV alternans conditioned by an enhanced dispersion of repolarization. The factors of hibernating species resistance to SDA and VF seem to be the safe and dynamically stable conduction and the low dispersion of repolarization.

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