The discontinuous nature of electrical propagation in cardiac muscle. Consideration of a quantitative model incorporating the membrane ionic properties and structural complexities. The ALZA distinguished lecture

Abstract

The propagation of excitation in cardiac muscle has generally been treated as though it occurred in a continuous structure. However, new evidence indicates that propagation in cardiac muscle often displays a discontinuous nature. In this paper, we consider the hypothesis that this previously unrecognized type of propagation is caused by recurrent discontinuities of effective axial resistivity which affect the membrane currents. The major implication is that the combination of discontinuities of axial resistivity at several size scales can produce most currently known cardiac conduction disturbances previously though to require spatial nonuniformities of the membrane properties. At present there is no appropriate model or simulation for propagation in anisotropic cardiac muscle. However, the recent quantitative description of the fast sodium current in voltage-clamped cardiac muscle membrane makes it possible, for the first time, to apply experimentally based quantitative membrane models to propagation in cardiac muscle. The major task now is to account for the functional role of the structural complexities of cardiac muscle. The importance of such a model is that it would establish how the membrane ionic currents and the complexities of cell and tissue structure interact to determine propagation in both normal and abnormal cardiac muscle.