Review of mechanisms by which electrical stimulation alters the transmembrane potential

Abstract

Electrical stimuli pace, cardiovert, or defibrillate the heart by changing transmembrane potential (deltaVm). Recent simulation studies provide insights into mechanisms by which stimuli establish deltaVm. This review attempts a nonmathematical description of these mechanisms. We start with the cable model in which the intracellular core conductor is bounded by a highly resistive and capacitive membrane that separates the intracellular and extracellular spaces. Intracellular and extracellular resistances are assumed to vary linearly with position. Although this model predicts anodal extracellular stimuli hyperpolarize adjacent tissue and cathodal extracellular stimuli depolarize that tissue, it fails to reproduce regions of opposite deltaVm distant from the electrodes. We then consider the sawtooth model in which microscopic discontinuities in intracellular resistance represent gap junctions. While model studies with such discontinuities demonstrate large deltaVm at cell ends, experimental validation of such deltaVm remains elusive. Extending the analysis to the two- and three-dimensional syncytium, we also consider the bidomain model in which intracellular, extracellular, and interstitial currents are explicitly characterized. Differences in resistance to these currents gives rise to virtual electrodes, which are experimentally observed regions of large deltaVm that arise distant from the stimulating electrode. Distant deltaVm regions are also evident when macroscopic discontinuities in intracellular resistance are introduced into the bidomain model. Such discontinuities are associated with clefts or scars that give rise to "secondary sources." Albeit the cable model offers remarkable insight the bidomain model and the concept of secondary sources provide a more complete understanding of membrane excitation, especially when combined into a unifying activating function.