A Simulation Study of Cellular Hypertrophy and Connexin Lateralization in Cardiac Tissue

Many cardiac diseases coincide with changes in cell size and shape. One example of such a disease is cardiac hypertrophy. It is established that cardiac impulse propagation depends on the cell size, as well as other factors, but interrelations between conduction velocity (CV), cell size, and gap junction (GJ) conductance (g(GJ)) are complex. Furthermore, cardiac diseases are often accompanied by connexin (Cx) lateralization. To analyze the effects of cell size and Cx lateralization in cardiac disease, a two-dimensional computer simulation of ventricular myocytes based on the Luo-Rudy model was used. Control cells (80 mu m/20 mu m (length/diameter)), long cells (160 mu m/20 mu m), and wide cells (80 mu m/40 mu m) were simulated as was a redistribution of lateral GJs (constant lateral g(GJ) and increased lateral g(GJ)). CV in long cells showed high stability, i.e., it declined very slowly when g(GJ) was gradually reduced. Wide cells, however, were more affected by reduced g(GJ), resulting in early transition to discontinuous propagation and low CV. Conduction block occurred earlier in enlarged cells than in control cells due to increased cell capacitance. Increased lateral g(GJ) stabilized longitudinal CV, which was a result of two-dimensional effects during planar wave propagation. Therefore, Cx lateralization may compensate for cardiac inhomogeneities. High lateral g(GJ) and enhanced cell diameter increased the susceptibility to conduction block at tissue expansion, providing a substrate for arrhythmia.