Loading Effect of Fibroblast-Myocyte Coupling on Resting Potential Impulse Propagation and Repolarization: Insights from a Microstructure Model

摘要

The numerous nonmyocytes present within the myocardium may establish electrical connections with myocytes through gap junctions, formed naturally or as a result of a cell therapy. The strength of the coupling and its potential impact on action potential characteristics and conduction is not well understood. This study uses computer simulation to investigate the load induced electrophysiological consequences of the coupling of myocytes with fibroblasts, where the fibroblast resting potential, density, distribution and coupling strength were varied. Conduction velocity (CV), upstroke velocity and action potential duration (APD) were analyzed for longitudinal and transverse impulse propagation in a two-dimensional microstructure tissue model, developed to represent a monolayer culture of cardiac cells covered by a layer of fibroblasts. The results show that: (1) At weak coupling (<0.25 nS), the myocyte resting potential was elevated, leading to CV up to 5% faster than control. (2) At intermediate coupling, the myocyte resting potential elevation saturated while the current flowing from the myocyte to the fibroblast progressively slowed down both CV and upstroke velocity. (3) At strong couplings (>8 nS), all the effects saturated. (4) APD90 was usually prolonged by 0–20 ms (up to 60–80 ms for high fibroblast density and coupling) by the coupling to fibroblasts. The changes in APD depended on the fibroblast resting potential. This complex, coupling dependent interaction of fibroblast and myocytes also has relevance to the integration of other nonmyocytes in the heart, such as those used in cellular therapies.