Electrotonic Cell-Cell Interactions in Cardiac Tissue: Effects on Action Potential Propagation and Repolarization

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.

Download Full-text

Cell Patterning: Interaction of Cardiac Myocytes and Fibroblasts in Three-Dimensional Culture

Microscopy and Microanalysis ◽

10.1017/s1431927608080021 ◽

2008 ◽

Vol 14 (2) ◽

pp. 117-125 ◽

Cited By ~ 42

Author(s):

Troy A. Baudino ◽

Alex McFadden ◽

Charity Fix ◽

Joshua Hastings ◽

Robert Price ◽

...

Keyword(s):

Cardiac Tissue ◽

Three Dimensional ◽

Normal Growth ◽

Cell Types ◽

Cell Interactions ◽

Cellular Interactions ◽

Cell Layers ◽

Cell Cell

Patterning of cells is critical to the formation and function of the normal organ, and it appears to be dependent upon internal and external signals. Additionally, the formation of most tissues requires the interaction of several cell types. Indeed, both extracellular matrix (ECM) components and cellular components are necessary for three-dimensional (3-D) tissue formationin vitro. Using 3-D cultures we demonstrate that ECM arranged in an aligned fashion is necessary for the rod-shaped phenotype of the myocyte, and once this pattern is established, the myocytes were responsible for the alignment of any subsequent cell layers. This is analogous to thein vivopattern that is observed, where there appears to be minimal ECM signaling, rather formation of multicellular patterns is dependent upon cell–cell interactions. Our 3-D culture of myocytes and fibroblasts is significant in that it modelsin vivoorganization of cardiac tissue and can be used to investigate interactions between fibroblasts and myocytes. Furthermore, we used rotational cultures to examine cellular interactions. Using these systems, we demonstrate that specific connexins and cadherins are critical for cell–cell interactions. The data presented here document the feasibility of using these systems to investigate cellular interactions during normal growth and injury.

Download Full-text

Spiral breakup in model equations of action potential propagation in cardiac tissue

Physical Review Letters ◽

10.1103/physrevlett.71.1103 ◽

1993 ◽

Vol 71 (7) ◽

pp. 1103-1106 ◽

Cited By ~ 228

Author(s):

Alain Karma

Keyword(s):

Action Potential ◽

Cardiac Tissue ◽

Action Potential Propagation ◽

Model Equations

Download Full-text

Calcium currents of ventricular cell pairs during action potential conduction

AJP Heart and Circulatory Physiology ◽

10.1152/ajpheart.1995.268.6.h2476 ◽

1995 ◽

Vol 268 (6) ◽

pp. H2476-H2486 ◽

Cited By ~ 6

Author(s):

R. Kumar ◽

R. W. Joyner

Keyword(s):

Action Potential ◽

Action Potentials ◽

Calcium Current ◽

Cardiac Tissue ◽

Calcium Currents ◽

Conduction Delay ◽

Ventricular Cells ◽

Action Potential Waveform ◽

Leader Cell ◽

Cell Cell

We have studied the L-type calcium current that occurs during action potential conduction between an isolated pair of guinea pig ventricular cells. To accomplish this, we first recorded action potentials from the leader cell (stimulated cell, cell 1) and the follower cell (nonstimulated cell, cell 2) with a fixed coupling resistance between the cells supplied by a coupling clamp circuit. We then applied these recorded action potentials as command potential waveforms for other cells studied in the voltage-clamp mode in which internal and external solutions that isolated the L-type calcium current were used. The action potential waveform of the leader cell had a rapid upstroke and then a partial repolarization during the conduction delay before activation of the follower cell. The L-type calcium current occurred with a large magnitude during the conduction delay for the leader cell but not for the follower cell. This leads to an asymmetry of calcium current for the two cells, with greater calcium current for the leader cell than for the follower cell. When we reversed the direction of conduction for cell 1 and cell 2 by stimulating cell 2, we found that application of these recorded waveforms for the action potentials for cell 1 and cell 2 to the voltage-clamped cells also reversed the asymmetry of the magnitude of the calcium current. We conclude that discontinuous conduction in cardiac tissue is associated with a directionally determined asymmetry in the magnitude of the calcium current, with the leader cell experiencing a greater peak calcium current than the follower cell.

Download Full-text

Simulation of Ectopic Pacemakers in the Heart: Multiple Ectopic Beats Generated by Reentry inside Fibrotic Regions

BioMed Research International ◽

10.1155/2015/713058 ◽

2015 ◽

Vol 2015 ◽

pp. 1-18 ◽

Cited By ~ 10

Author(s):

Bruno Gouvêa de Barros ◽

Rodrigo Weber dos Santos ◽

Marcelo Lobosco ◽

Sergio Alonso

Keyword(s):

Action Potential ◽

Discrete Model ◽

Animal Studies ◽

Cardiac Fibrosis ◽

Cardiac Tissue ◽

Microscopic Model ◽

Ectopic Beat ◽

Action Potential Propagation ◽

Ectopic Beats ◽

Heterogeneous Tissue

The inclusion of nonconducting media, mimicking cardiac fibrosis, in two models of cardiac tissue produces the formation of ectopic beats. The fraction of nonconducting media in comparison with the fraction of healthy myocytes and the topological distribution of cells determines the probability of ectopic beat generation. First, a detailed subcellular microscopic model that accounts for the microstructure of the cardiac tissue is constructed and employed for the numerical simulation of action potential propagation. Next, an equivalent discrete model is implemented, which permits a faster integration of the equations. This discrete model is a simplified version of the microscopic model that maintains the distribution of connections between cells. Both models produce similar results when describing action potential propagation in homogeneous tissue; however, they slightly differ in the generation of ectopic beats in heterogeneous tissue. Nevertheless, both models present the generation of reentry inside fibrotic tissues. This kind of reentry restricted to microfibrosis regions can result in the formation of ectopic pacemakers, that is, regions that will generate a series of ectopic stimulus at a fast pacing rate. In turn, such activity has been related to trigger fibrillation in the atria and in the ventricles in clinical and animal studies.

Download Full-text