Cardiac Impulse Propagation: An Integrated View.

Two principal mechanisms have been proposed to explain impulse propagation in cardiac tissue. The first is low-resistance gap-junctional coupling, which explains many experimental observations but does not fully account for all findings, such as those in connexin 43-knockout mouse experiments. The second is ephaptic coupling, in which myocytes interact via electric fields in the narrow extracellular cleft between cells and that can, in principle, support conduction even when effective gap-junctional conductance is low or absent. In this review, we summarize the theoretical insights from computational modeling studies and experimental evidence supporting ephaptic coupling. Although experimental evidence for ephaptic coupling remains indirect and limited, we argue that, as with all biological systems, the heart may utilize redundant coupling mechanisms to ensure the robustness of conduction and normal cardiac function. In other words, gap junction coupling and ephaptic coupling are not mutually exclusive but instead function in a synergistic and complementary way to optimize cardiac function across a large physiological range.