scholarly journals Optimisation of a Generic Ionic Model of Cardiac Myocyte Electrical Activity

2013 ◽  
Vol 2013 ◽  
pp. 1-20 ◽  
Author(s):  
Tianruo Guo ◽  
Amr Al Abed ◽  
Nigel H. Lovell ◽  
Socrates Dokos
Keyword(s):  
Action Potential ◽  
Time Course ◽  
Cardiac Myocyte ◽  
Cardiac Tissue ◽  
Ionic Currents ◽  
Experimental Information ◽  
Electrical Stimulus ◽  
Right Atrial ◽  
Ionic Model ◽  
Multiple Datasets

A generic cardiomyocyte ionic model, whose complexity lies between a simple phenomenological formulation and a biophysically detailed ionic membrane current description, is presented. The model provides a user-defined number of ionic currents, employing two-gate Hodgkin-Huxley type kinetics. Its generic nature allows accurate reconstruction of action potential waveforms recorded experimentally from a range of cardiac myocytes. Using a multiobjective optimisation approach, the generic ionic model was optimised to accurately reproduce multiple action potential waveforms recorded from central and peripheral sinoatrial nodes and right atrial and left atrial myocytes from rabbit cardiac tissue preparations, under different electrical stimulus protocols and pharmacological conditions. When fitted simultaneously to multiple datasets, the time course of several physiologically realistic ionic currents could be reconstructed. Model behaviours tend to be well identified when extra experimental information is incorporated into the optimisation.

A computationally efficient electrophysiological model of human ventricular cells

2002 ◽  
Vol 282 (6) ◽  
pp. H2296-H2308 ◽  
Author(s):  
O. Bernus ◽  
R. Wilders ◽  
C. W. Zemlin ◽  
H. Verschelde ◽  
A. V. Panfilov
Keyword(s):  
Action Potential ◽  
Cardiac Tissue ◽  
Spiral Wave ◽  
Ionic Currents ◽  
Average Frequency ◽  
Computationally Efficient ◽  
Variable Model ◽  
Potential Shape ◽  
Ventricular Cells ◽  
Ventricular Tissue

Recent experimental and theoretical results have stressed the importance of modeling studies of reentrant arrhythmias in cardiac tissue and at the whole heart level. We introduce a six-variable model obtained by a reformulation of the Priebe-Beuckelmann model of a single human ventricular cell. The reformulated model is 4.9 times faster for numerical computations and it is more stable than the original model. It retains the action potential shape at various frequencies, restitution of action potential duration, and restitution of conduction velocity. We were able to reproduce the main properties of epicardial, endocardial, and M cells by modifying selected ionic currents. We performed a simulation study of spiral wave behavior in a two-dimensional sheet of human ventricular tissue and showed that spiral waves have a frequency of 3.3 Hz and a linear core of ∼50-mm diameter that rotates with an average frequency of 0.62 rad/s. Simulation results agreed with experimental data. In conclusion, the proposed model is suitable for efficient and accurate studies of reentrant phenomena in human ventricular tissue.

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.

Genesis of the monophasic action potential: role of interstitial resistance and boundary gradients

2004 ◽  
Vol 286 (4) ◽  
pp. H1370-H1381 ◽  
Author(s):  
Joseph V. Tranquillo ◽  
Michael R. Franz ◽  
Björn C. Knollmann ◽  
Alexandra P. Henriquez ◽  
Doris A. Taylor ◽  
...  
Keyword(s):  
Action Potential ◽  
Time Course ◽  
Cardiac Tissue ◽  
Mechanical Load ◽  
Critical Role ◽  
Applied Pressure ◽  
Three Dimensional ◽  
Membrane Dynamics ◽  
Monophasic Action Potential ◽  
Tissue Properties

The extracellular potential at the site of a mechanical deformation has been shown to resemble the underlying transmembrane action potential, providing a minimally invasive way to access membrane dynamics. The biophysical factors underlying the genesis of this signal, however, are still poorly understood. With the use of data from a recent experimental study in a murine heart, a three-dimensional anisotropic bidomain model of the mouse ventricular free wall was developed to study the currents and potentials resulting from the application of a point mechanical load on cardiac tissue. The applied pressure is assumed to open nonspecific pressure-sensitive channels depolarizing the membrane, leading to monophasic currents at the electrode edge that give rise to the monophasic action potential (MAP). The results show that the magnitude and the time course of the MAP are reproduced only for certain combinations of local or global intracellular and interstitial resistances that form a resting tissue length constant that, if applied over the entire domain, is smaller than that required to match the wave speed. The results suggest that the application of pressure not only causes local depolarization but also changes local tissue properties, both of which appear to play a critical role in the genesis of the MAP.

scholarly journals New insights into application of cardiac monophasic action potential

2010 ◽  
pp. 645-650
Author(s):  
S-G Yang ◽  
O Kittnar
Keyword(s):  
Action Potential ◽  
Time Course ◽  
Cardiac Tissue ◽  
Femoral Vein ◽  
Myocardial Cell ◽  
Monophasic Action Potential ◽  
Seldinger Technique ◽  
Accurate Information ◽  
Length Changes

Monophasic action potential (MAP) recording plays an important role in a more direct view of human myocardial electrophysiology under both physiological and pathological conditions. The procedure of MAP measuring can be simply performed using the Seldinger technique, when MAP catheter is inserted through femoral vein into the right ventricle or through femoral artery to the left ventricle. The MAP method represents a very useful tool for electrophysiological research in cardiology. Its crucial importance is based upon the fact that it enables the study of the action potential (AP) of myocardial cell in vivo and, therefore, the study of the dynamic relation of this potential with all the organism variables. This can be particularly helpful in the case of arrhythmias. There are no doubts that physiological MAP recording accuracy is almost the same as transmembrane AP as was recently confirmed by anisotropic bidomain model of the cardiac tissue. MAP recording devices provide precise information not only on the local activation time but also on the entire local repolarization time course. Although the MAP does not reflect the absolute amplitude or upstroke velocity of transmembrane APs, it delivers highly accurate information on AP duration and configuration, including early afterdepolarizations as well as relative changes in transmembrane diastolic and systolic potential changes. Based on available data, the MAP probably reflects the transmembrane voltage of cells within a few millimeters of the exploring electrode. Thus MAP recordings offer the opportunity to study a variety of electrophysiological phenomena in the in situ heart (including effects of cycle length changes and antiarrhythmic drugs on AP duration).

Electrical remodeling of the epicardial border zone in the canine infarcted heart: a computational analysis

2003 ◽  
Vol 284 (1) ◽  
pp. H372-H384 ◽  
Author(s):  
Candido Cabo ◽  
Penelope A. Boyden
Keyword(s):  
Action Potential ◽  
Ionic Currents ◽  
Propagation Model ◽  
Border Zone ◽  
Delayed Rectifier ◽  
Antiarrhythmic Agents ◽  
Ionic Model ◽  
Infarcted Heart ◽  
A Cell ◽  
The Difference

The density and kinetics of several ionic currents of cells isolated from the epicardial border zone of the infarcted heart (IZs) are markedly different from cells from the noninfarcted canine epicardium (NZs). To understand how these changes in channel function affect the action potential of the IZ cell as well as its response to antiarrhythmic agents, we developed a new ionic model of the action potential of a cell that survives in the infarct (IZ) and one of a normal epicardial cell (NZ) using formulations based on experimental measurements. The difference in action potential duration (APD) between NZ and IZ cells during steady-state stimulation (basic cycle length = 250 ms) was 6 ms (156 ms in NZ and 162 ms in IZ). However, because IZs exhibit postrepolarization refractoriness, the difference in the effective refractory period (ERP), calculated using a propagation model of a single fiber of 100 cells, was 43 ms (156 ms in NZ and 199 ms in IZ). Either an increase in L-type Ca2+ current (to simulate the effects of BAY Y5959) or a decrease of both or either delayed rectifier currents (e.g., to simulate the effects of azimilide, sotalol, and chromanol) had significant effects on NZ ERP. In contrast, the effects of these agents in IZs were minor, in agreement with measurements in the in situ canine infarcted heart. Therefore 1) because IZs exhibit postrepolarization refractoriness, conclusions drawn from APD measurements cannot be extrapolated directly to ERPs; 2) ionic currents that are the major determinants of APD and the ERP in NZs are less important in IZs; and 3) differential effects of either BAY Y5959 or azimilide in NZs versus IZs are predicted to decrease ERP dispersion and in so doing prevent initiation of arrhythmias in a substrate of inhomogeneous APD/ERPs.

Nonlinear changes of transmembrane potential caused by defibrillation shocks in strands of cultured myocytes

2000 ◽  
Vol 278 (3) ◽  
pp. H688-H697 ◽  
Author(s):  
Vladimir G. Fast ◽  
Stephan Rohr ◽  
Raymond E. Ideker
Keyword(s):  
Action Potential ◽  
Transmembrane Potential ◽  
Cardiac Tissue ◽  
Ionic Currents ◽  
Time Dependent ◽  
Uniform Field ◽  
Shock Strength ◽  
Different Types ◽  
Opposite Strand ◽  
Negative Time

Organization of cardiac tissue into cell strands and layers has been implicated in changes of transmembrane potential (Δ V m) during defibrillation. To determine the shock-induced Δ V m in such structures, cell strands of variable width [strand width (SW) = 0.15–2 mm] were grown in culture. Uniform-field shocks with variable strength [shock strength (SS) = 2–50 V/cm] were applied across strands during the action potential (AP) plateau, and Δ V m were measured optically. Three different types of Δ V m were observed. Small Δ V m [<40%AP amplitude (APA)] were linearly dependent on SS and SW and were symmetrically distributed about a strand centerline with maximal positive and negative Δ V m on opposite strand sides being equal. Intermediate Δ V m (<200%APA) were strongly asymmetric with negative Δ V m > positive Δ V m because of a negative time-dependent shift of V m at the depolarized side of the strands. For large Δ V m (>200%APA), a second time-dependent shift of V m to more positive levels was observed in the hyperpolarized portions of strands, causing reduction of the Δ V m asymmetry. We conclude that during application of shocks to cell strands during the AP plateau, passive changes of V m were followed by two voltage- and time-dependent shifts of V m, possibly reflecting changes of ionic currents or membrane electroporation.

scholarly journals Canine Myocytes Represent a Good Model for Human Ventricular Cells Regarding Their Electrophysiological Properties

2021 ◽  
Vol 14 (8) ◽  
pp. 748
Author(s):  
Péter P. Nánási ◽  
Balázs Horváth ◽  
Fábián Tar ◽  
János Almássy ◽  
Norbert Szentandrássy ◽  
...  
Keyword(s):  
Action Potential ◽  
Time Course ◽  
Laboratory Animals ◽  
Delayed Rectifier ◽  
Ion Currents ◽  
Human Cardiomyocytes ◽  
Ventricular Cells ◽  
Repolarization Reserve ◽  
Electrophysiological Studies ◽  
K Current

Due to the limited availability of healthy human ventricular tissues, the most suitable animal model has to be applied for electrophysiological and pharmacological studies. This can be best identified by studying the properties of ion currents shaping the action potential in the frequently used laboratory animals, such as dogs, rabbits, guinea pigs, or rats, and comparing them to those of human cardiomyocytes. The authors of this article with the experience of three decades of electrophysiological studies, performed in mammalian and human ventricular tissues and isolated cardiomyocytes, summarize their results obtained regarding the major canine and human cardiac ion currents. Accordingly, L-type Ca2+ current (ICa), late Na+ current (INa-late), rapid and slow components of the delayed rectifier K+ current (IKr and IKs, respectively), inward rectifier K+ current (IK1), transient outward K+ current (Ito1), and Na+/Ca2+ exchange current (INCX) were characterized and compared. Importantly, many of these measurements were performed using the action potential voltage clamp technique allowing for visualization of the actual current profiles flowing during the ventricular action potential. Densities and shapes of these ion currents, as well as the action potential configuration, were similar in human and canine ventricular cells, except for the density of IK1 and the recovery kinetics of Ito. IK1 displayed a largely four-fold larger density in canine than human myocytes, and Ito recovery from inactivation displayed a somewhat different time course in the two species. On the basis of these results, it is concluded that canine ventricular cells represent a reasonably good model for human myocytes for electrophysiological studies, however, it must be borne in mind that due to their stronger IK1, the repolarization reserve is more pronounced in canine cells, and moderate differences in the frequency-dependent repolarization patterns can also be anticipated.

scholarly journals Statistical Approach to Incorporating Experimental Variability into a Mathematical Model of the Voltage-Gated Na+ Channel and Human Atrial Action Potential

Cells ◽  
2021 ◽  
Vol 10 (6) ◽  
pp. 1516
Author(s):  
Daniel Gratz ◽  
Alexander J Winkle ◽  
Seth H Weinberg ◽  
Thomas J Hund
Keyword(s):  
Action Potential ◽  
Mathematical Models ◽  
Cardiac Myocyte ◽  
Population Level ◽  
Na Channel ◽  
Model Parameters ◽  
Healthy Population ◽  
Experimental Measurements ◽  
Voltage Gated ◽  
Experimental Variability

The voltage-gated Na+ channel Nav1.5 is critical for normal cardiac myocyte excitability. Mathematical models have been widely used to study Nav1.5 function and link to a range of cardiac arrhythmias. There is growing appreciation for the importance of incorporating physiological heterogeneity observed even in a healthy population into mathematical models of the cardiac action potential. Here, we apply methods from Bayesian statistics to capture the variability in experimental measurements on human atrial Nav1.5 across experimental protocols and labs. This variability was used to define a physiological distribution for model parameters in a novel model formulation of Nav1.5, which was then incorporated into an existing human atrial action potential model. Model validation was performed by comparing the simulated distribution of action potential upstroke velocity measurements to experimental measurements from several different sources. Going forward, we hope to apply this approach to other major atrial ion channels to create a comprehensive model of the human atrial AP. We anticipate that such a model will be useful for understanding excitability at the population level, including variable drug response and penetrance of variants linked to inherited cardiac arrhythmia syndromes.

Linear transformations extract parameters of ionic currents and action potential features from pseudo-ECG in cardiomyocyte models

2020 ◽  
Author(s):  
Salim Baigildin ◽  
Konstantin Ushenin ◽  
Aigul Fabarisova ◽  
Marat Bogdanov ◽  
Olga Solovyeva
Keyword(s):  
Action Potential ◽  
Ionic Currents ◽  
Linear Transformations

Calcium Dynamics and Compartmentalization in Leech Neurons

2005 ◽  
Vol 94 (6) ◽  
pp. 4430-4440 ◽  
Author(s):  
Sofija Andjelic ◽  
Vincent Torre
Keyword(s):  
Information Processing ◽  
Action Potential ◽  
Action Potentials ◽  
Time Course ◽  
Ccd Camera ◽  
Calcium Dynamics ◽  
Single Action ◽  
Single Action Potential ◽  
Calcium Indicator ◽  
Mechanosensory Neurons

Calcium dynamics in leech neurons were studied using a fast CCD camera. Fluorescence changes (Δ F/ F) of the membrane impermeable calcium indicator Oregon Green were measured. The dye was pressure injected into the soma of neurons under investigation. Δ F/ F caused by a single action potential (AP) in mechanosensory neurons had approximately the same amplitude and time course in the soma and in distal processes. By contrast, in other neurons such as the Anterior Pagoda neuron, the Annulus Erector motoneuron, the L motoneuron, and other motoneurons, APs evoked by passing depolarizing current in the soma produced much larger fluorescence changes in distal processes than in the soma. When APs were evoked by stimulating one distal axon through the root, Δ F/ F was large in all distal processes but very small in the soma. Our results show a clear compartmentalization of calcium dynamics in most leech neurons in which the soma does not give propagating action potentials. In such cells, the soma, while not excitable, can affect information processing by modulating the sites of origin and conduction of AP propagation in distal excitable processes.

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