Propagation Delays Across Cardiac Gap Junctions and their Reflection in Extracellular Potentials: A Simulation Study

Abstract

Propagation Delays and Extracellular Potentials. There is increasing evidence that the complex microscopic structure of the myocardium (distribution of cell‐to‐cell connections) plays an important role in determining propagation of excitation in cardiac muscle. To study this phenomenon, extracellular potentials must be measured with microscopic spatial resolution in cardiac tissue. In this article, the relationships between propagation delays across cardiac gap junctions and extracellular potential waveforms are analyzed using a one‐dimensional model of a propagating action potential, for different degrees of cellular coupling. The central question addressed by this study is whether propagation discontinuities at the cellular level can be detected by microscopic resolution extracellular potential measurements, and whether the discrete junctional propagation delay can be measured by extracellular electrodes. Results demonstrate that the discontinuous nature of propagation at the cellular level is reflected as nonuniformities in the local (microscopic) conduction velocity measured by extracellular electrodes with microscopic resolution (interelectrode distance of 50 μm); the degree of nonuniformities in the microscopic velocity is amplified as a result of decreased cellular coupling. These observations are in agreement with recent experimental findings. Propagation time between the middle regions of adjacent cells can be estimated accurately from extracellular potentials at these sites. In contrast, two extracellular electrodes positioned at opposite ends of the gap junction (electrode spacing of 5 μm) cannot detect or measure the propagation delay across the junction. This limitation results from the fact that extracellular potentials do not reflect only the localized underlying electrical sources on such a microscopic scale. As cells become less coupled, irregularities appear in the unipolar extracellular potential waveforms. The simulations relate these irregularities to depolarization of individual cells in the fiber. Under the condition of reduced cellular coupling, the depolarization events of neighboring cells are sufficiently separated in time to appear as separate events in the extracellular waveforms.