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).

scholarly journals Generation of Monophasic Action Potentials and Intermediate Forms

2020 ◽  
Author(s):  
Shahriar Iravanian ◽  
Ilija Uzelac ◽  
Conner Herndon ◽  
Jonathan J Langberg ◽  
Flavio H Fenton
Keyword(s):  
Action Potential ◽  
Cardiac Electrophysiology ◽  
Cardiac Tissue ◽  
Signal Generation ◽  
Monophasic Action Potential ◽  
Model Parameters ◽  
Pass Filter ◽  
Tissue Properties ◽  
Main Challenge ◽  
Potential Map

ABSTRACTThe Monophasic Action Potential (MAP) is a near replica of the transmembrane potential recorded when an electrode is pushed firmly against cardiac tissue. Despite its many practical uses, the mechanism of MAP signal generation and the reason it is so different from unipolar recordings is not completely known and is a matter of controversy. It is hypothesized that partial depolarization of the cells directly underneath the electrode contributes to the generation of MAP signals. In this paper, we describe a parametric, semi-quantitative method to generate realistic MAP and intermediate forms – multiphasic electrograms different from an ideal MAP – that does not require the partial depolarization hypothesis. The key ideas of our method are the formation of junctional spaces, i.e., electrically isolated pockets between the surface of an electrode and tissue, and the presence of a complex network of passive components that acts as a high-pass filter to distort the signal that reaches the recording amplifier. The passive network is formed by the interaction between the passive tissue properties and the double-layer capacitance of electrodes. We show that it is possible to generate different electrograms by the change of the model parameters and that both the MAP and intermediate forms reside on a continuum of signals. Our model helps to decipher the mechanisms of signal generation and can lead to a better design for electrodes, recording amplifiers, and experimental setups.SIGNIFICANCERecording the Monophasic Action Potential (MAP) is potentially very useful in both experimental and clinical cardiac electrophysiology and can provide valuable information about the repolarization phase of the action potential. However, despite its benefits, it currently has only a small and niche role. The main challenge is the technical difficulties of recording an ideal MAP. Our results provide a better understanding of the mechanisms of the generation of cardiac electrograms and may help to optimize experiments and improve tools to achieve the full potentials of recording the MAP signals.

scholarly journals Strength-duration relationship as a tool to prioritize cardiac tissue properties that govern electrical excitability

2019 ◽  
Vol 317 (1) ◽  
pp. H13-H25 ◽  
Author(s):  
Michael N. Sayegh ◽  
Natasha Fernandez ◽  
Hee Cheol Cho
Keyword(s):  
Cardiac Tissue ◽  
Three Dimensional ◽  
Assessment Tools ◽  
Electrical Strength ◽  
Design Parameters ◽  
Electrical Excitability ◽  
Cell Alignment ◽  
Tissue Properties ◽  
Duration Relationship

Gaps exist in the availability of in vitro functional assessment tools that can emulate the integration of regenerative cells and tissues to the host myocardium. We use strength-duration relationships of electrically stimulated two- and three-dimensional myocardial constructs to study the effects of pacing frequency, culture dimensions, anisotropic cell alignment, fibroblast content, and pacemaker phenotype on electrical excitability. Our study delivers electrical strength-duration as a quantifiable parameter to evaluate design parameters of engineered cardiac tissue constructs.

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.

scholarly journals Transmural recording of monophasic action potentials

2002 ◽  
Vol 282 (3) ◽  
pp. H855-H861 ◽  
Author(s):  
Xiaohong Zhou ◽  
Jian Huang ◽  
Raymond E. Ideker
Keyword(s):  
Guinea Pig ◽  
Action Potential ◽  
Refractory Period ◽  
Time Course ◽  
Monophasic Action Potential ◽  
Papillary Muscles ◽  
Transmembrane Potentials ◽  
Potential Map ◽  
Monophasic Action Potentials ◽  
Injury Potential

To investigate the possibility of transmural recording of repolarization through the ventricular wall, KCl monophasic action potential (MAP) electrodes positioned along plunge needles were developed and tested. The MAP electrode consists of a silver wire surrounded by agarose gel containing KCl, which slowly eluted into the adjacent tissue to depolarize it. In six dogs, a plunge needle containing three KCl MAP electrodes was inserted into the left ventricle to simultaneously record from the subepicardium, midwall, and subendocardium. In six pigs, eight plunge needles containing three KCl MAP electrodes and two plunge needles containing similar electrodes except for the absence of KCl were inserted into the ventricles. In three guinea pig papillary muscles, a KCl electrode was used to record MAPs along with two microelectrodes for recording transmembrane potentials. Transmural MAP recordings could be made for >1 h in dogs and >2 h in pigs with a significant decrease in MAP amplitude over time but without a significant change in MAP duration. With the electrodes without KCl in pigs, the injury potentials subsided in <30 min. When the pacing rate was changed to alter the action potential duration and refractory period in dogs, the MAP duration correlated with the local effective refractory period ( r = 0.94). The time course of the MAP duration recorded with a KCl MAP electrode in guinea pig papillary muscles corresponded well with that of the transmembrane potential recorded with an adjacent microelectrode. It is possible to record transmural repolarization of the ventricles with KCl MAP electrodes on plunge needles. The MAP is caused by the KCl rather than being a nonspecific injury potential.

Effects of early afterdepolarizations on reentry in cardiac tissue: a simulation study

2007 ◽  
Vol 292 (6) ◽  
pp. H3089-H3102 ◽  
Author(s):  
Ray B. Huffaker ◽  
James N. Weiss ◽  
Boris Kogan
Keyword(s):  
Action Potential ◽  
Cardiac Tissue ◽  
Genetic Diseases ◽  
Three Dimensional ◽  
New Wave ◽  
Early Afterdepolarizations ◽  
Heart Rates ◽  
Torsades Des Pointes ◽  
Repolarization Reserve ◽  
Inward Currents

Early afterdepolarizations (EADs) are classically generated at slow heart rates when repolarization reserve is reduced by genetic diseases or drugs. However, EADs may also occur at rapid heart rates if repolarization reserve is sufficiently reduced. In this setting, spontaneous diastolic sarcoplasmic reticulum (SR) Ca release can facilitate cellular EAD formation by augmenting inward currents during the action potential plateau, allowing reactivation of the window L-type Ca current to reverse repolarization. Here, we investigated the effects of spontaneous SR Ca release-induced EADs on reentrant wave propagation in simulated one-, two-, and three-dimensional homogeneous cardiac tissue using a version of the Luo-Rudy dynamic ventricular action potential model modified to increase the likelihood of these EADs. We found: 1) during reentry, nonuniformity in spontaneous SR Ca release related to subtle differences in excitation history throughout the tissue created adjacent regions with and without EADs. This allowed EADs to initiate new wavefronts propagating into repolarized tissue; 2) EAD-generated wavefronts could propagate in either the original or opposite direction, as a single new wave or two new waves, depending on the refractoriness of tissue bordering the EAD region; 3) by suddenly prolonging local refractoriness, EADs caused rapid rotor displacement, shifting the electrical axis; and 4) rapid rotor displacement promoted self-termination by collision with tissue borders, but persistent EADs could regenerate single or multiple focal excitations that reinitiated reentry. These findings may explain many features of Torsades des pointes, such as perpetuation by focal excitations, rapidly changing electrical axis, frequent self-termination, and occasional degeneration to fibrillation.

scholarly journals Simultaneous smoothing and detection of topological units of genome organization from sparse chromatin contact count matrices with matrix factorization

2020 ◽  
Author(s):  
Da-Inn Lee ◽  
Sushmita Roy
Keyword(s):  
High Throughput ◽  
Matrix Factorization ◽  
Genome Organization ◽  
Time Course ◽  
Critical Role ◽  
Chromatin Modification ◽  
Three Dimensional ◽  
Enrichment Analysis ◽  
Developmental Time ◽  
Chromosome Conformation

AbstractThe three-dimensional (3D) organization of the genome plays a critical role in gene regulation for diverse normal and disease processes. High-throughput chromosome conformation capture (3C) assays, such as Hi-C, SPRITE, GAM, and HiChIP, have revealed higher-order organizational units such as topologically associating domains (TADs), which can shape the regulatory landscape governing downstream phenotypes. Analysis of high-throughput 3C data depends on the sequencing depth, which directly affects the resolution and the sparsity of the generated 3D contact count map. Identification of TADs remains a significant challenge due to the sensitivity of existing methods to resolution and sparsity. Here we present GRiNCH, a novel matrix-factorization-based approach for simultaneous TAD discovery and smoothing of contact count matrices from high-throughput 3C data. GRiNCH TADs are enriched in known architectural proteins and chromatin modification signals and are stable to the resolution, and sparsity of the input data. GRiNCH smoothing improves the recovery of structure and significant interactions from low-depth datasets. Furthermore, enrichment analysis of 746 transcription factor motifs in GRiNCH TADs from developmental time-course and cell-line Hi-C datasets predicted transcription factors with potentially novel genome organization roles. GRiNCH is a broadly applicable tool for the analysis of high throughput 3C datasets from a variety of platforms including SPRITE and HiChIP to understand 3D genome organization in diverse biological contexts.

EFFECT OF CARDIAC TISSUE ANISOTROPY ON THREE-DIMENSIONAL ELECTRICAL ACTION POTENTIAL PROPAGATION

2010 ◽  
Vol 24 (17) ◽  
pp. 1847-1853 ◽  
Author(s):  
ZHI ZHU HE ◽  
JING LIU
Keyword(s):  
Action Potential ◽  
Computational Models ◽  
Cardiac Tissue ◽  
Three Dimensional ◽  
Propagation Model ◽  
Spatial Inhomogeneity ◽  
Cardiac Tissues ◽  
Action Potential Propagation ◽  
Self Similar ◽  
Tissue Anisotropy

A three-dimensional (3D) electrical action potential propagation model is developed to characterize the integrated effect of cardiac tissue structure using a homogenous function with a spatial inhomogeneity. This method may be more effective for bridging the gap between computational models and experimental data for cardiac tissue anisotropy. A generalized 3D eikonal relation considering anisotropy and a self-similar evolution solution of such a relation are derived to identify the effect of anisotropy and predict the anisotropy-induced electrical wave propagation instabilities. Furthermore, the phase field equation is introduced to obtain the complex three-dimensional numerical solution of the new correlation. The present results are expected to be valuable for better understanding the physiological behavior of cardiac tissues.

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