An axonal model for analysis of ionic concentration alterations induced by high frequency electrical stimulations

The nerve conduction blocking by high frequency biphasic (HFB) electrical stimulations has many potentially valuable clinical applications, but its safety margins require further evaluations. This simulation study aimed to construct an axonal model to investigate the effects of HFB electrical currents on the axonal conductibility and ionic concentrations. The axonal model was constructed in the software of NEURON by incorporating the McIntyre-Richardson-Grill model's geometries, Frankenhaeuser-Huxley and passive equations, ionic diffusion mechanism, and sodium pump activities. The applied 5 s HFB electrical stimulation apparently altered the axon's conductibility, which manifested lowered AP amplitudes, elevated resting membrane potentials, and delayed AP initiation times. These changes did not gain complete recoveries within the observed 55 s period, and showed to be mainly attributed to the induced alterations in ionic concentrations of nodal [Na+]i, nodal [K+]i and para-nodal [Na+]o. The results implied that the inter-nodal segments played a buffering role against changes of intracellular nodal ionic concentrations, and the intra-cellular ionic concentrations recovered at the price of increases in para-nodal [Na+]o. This study provided more information useful for evaluating the safety margins of nerve conduction blocking by HFB electrical stimulations, and are valuable for designing more safe and applicable protocols.