Relating the Sodium Current and Conductance to the Shape of Transmembrane and Extracellular Potentials by Simulation: Effects of Propagation Boundaries

The purpose of this paper is to describe how the transmembrane and extracellular potential waveforms, and their derivatives, are related to each other and to the sodium current and conductance in propagating cardiac action potentials. The results show that the shape of the transmembrane potential and the kinetics of the sodium current and conductance are highly determined by boundary effects at sites where impulse conduction begins and where it ends at a collision or an anatomical end. These propagation nonuniformities produced a relationship between Vmax and the internal membrane variables gNa and INa that is just the opposite of the classical relation between Vmax and the magnitude of the sodium current. For example, in these cases, both peak INa and the area under the gNa curve decreased when Vmax increased. In addition, Vmax, was shown to coincide in time with the maximum rate of increase of gNa and INa. The maximum negative slope of the extracellular waveform coincided in time with Vmax of the transmembrane potential for all shapes of the waveforms. Therefore, either the maximum negative slope of the extracellular waveform or Vmax of the action potential provides a time marker for the same underlying depolarizing event, i.e., the maximum rate of increase of the depolarizing current and its conductance.