Model Analysis of Post-Stimulation Effect on Axonal Conduction and Block.

Abstract

To reveal the possible contribution of changes in membrane ion concentration gradients and ion pump activity to axonal conduction/block induced by long-duration electrical stimulation. A new model for conduction and block of unmyelinated axons based on the classical Hodgkin-Huxley (HH) equations is developed to include changes in Na+ and K+ concentrations and ion pumps. The effect of long-duration stimulation on axonal conduction/block is analyzed by computer simulation using this new model. The new model successfully simulates initiation, propagation, and block of action potentials induced by short-duration (multiple milliseconds) stimulations that do not significantly change the ion concentrations in the classical HH model. In addition, the activity-dependent effects such as action potential attenuation and broadening observed in animal studies are also successfully simulated by the new model. Finally, the model successfully simulates axonal block occurring after terminating a long-duration (multiple seconds) direct current (DC) stimulation as observed in recent animal studies and reveals 3 different mechanisms for the post-DC block of axonal conduction. Ion concentrations and pumps play an important role in post-stimulation effects and activity-dependent effects on axonal conduction/block. The duration of stimulation is a determinant factor because it influences the total charges applied to the axon, which in turn determines the ion concentrations inside and outside the axon. Despite recent clinical success of many neurostimulation therapies, the effects of long-duration stimulation on axonal conduction/block are poorly understood. This new model could significantly impact our understanding of the mechanisms underlying different neurostimulation therapies.