A model study of the effects of the discrete cellular structure on electrical propagation in cardiac tissue.

Abstract

The effects of the discrete cellular structure on propagation of electrical excitation in cardiac muscle were studied in a one-dimensional fiber model containing a periodic intercalated disk structure. Globally, the macroscopic velocity of propagation follows the behavior associated with propagation in a continuous tissue (except for high values of disk resistance). In addition, the computed spatial extracellular potential along the fiber is a smooth biphasic waveform and does not reflect the underlying discrete cellular structure of the tissue. Other results of the simulations demonstrate the discontinuous nature of propagation and the importance of the structure in arrhythmogenesis. Vmax displays a biphasic behavior as a function of increasing intercalated disk resistance. An initial "paradoxical" increase in Vmax (with a simultaneous decrease in conduction velocity) is followed by a decrease that leads to decremental propagation and conduction block. The time constant of the foot of the action potential (tau foot) increases monotonically with increasing intercalated disk resistance. An increase in the leakage current to extracellular space brings about a significant decrease in the action potential duration and a loss of the plateau. This major effect is accompanied by a relatively smaller decrease in conduction velocity. Collision of two activation wavefronts results in a significant (100%) increase in Vmax and a very small (0.6%) decrease in tau foot.

Autocrine Regulation of Myocyte Cx43 Expression by VEGF

“…This dependence is much less apparent in a continuous system in which gap junction resistance is low relative to myoplasm resistance than in a discontinuous system in which gap junction resistance predominates. The theoretical simulations of Rudy and Quan 13 and Spach et al 14 fit experimental data in anisotropic rat cell cultures. 15 For these reasons, a significant decrease in dV/ dt max would not likely be seen in well-coupled myocytes subjected to pulsatile stretch or stimulated to increase Cx43 expression by addition of exogenous mediators.…”

“…These results suggest that no major changes in ion channels involved in propagation (I Na and possibly I L,Ca ) 12 occurred in response to stretch. In a modeling study, Rudy and Quan 13 showed a clear dependence of average dV/dt max of the action potential upstroke on coupling resistance. This dependence was steep in partially uncoupled cells but flat in well-coupled tissue.…”

A Cell-Based Framework for Numerical Modeling of Electrical Conduction in Cardiac Tissue

“…The electrical conduction of the heart is believed to depend on direct cell-to-cell contact realized in terms of gap junctions (e.g., [35][36][37]). These connections are reduced under heart failure, resulting in impaired conduction velocity that may in turn increase the probability of arrhythmias (e.g., [37,38]).…”

Differential Effects of a Segment of Slow Conduction on Reentrant Ventricular Tachycardia in the Rabbit Heart

“…This observation is difficult to explain by an increased junctional resistance alone. Some studies have suggested that changes in cell-tocell communication may also have an indirect effect on the action potential 25,42,43 and that heptanol may change the capacitance of the membrane. 39,43 Therefore, it remains uncertain whether the prolongation of the partially excitable period is due to electrical uncoupling alone or whether a change in availability or kinetics of the fast sodium channels may also play a role.…”