Effect of electroporation on neuronal excitability under H-FIRE pulses

The traditional Hodgkin-Huxley (HH) model is mainly applicable to neuronal excitability under low electric fields but ails at high field intensities. In this study, an improved HH model incorporating electroporation (EP) current was proposed. Simulation results showed that under a classical IRE pulse (100 μs, 440 V/cm), EP current evoked an action potential (AP) with a peak of 18.38 mV at t = 2.98 ms; whereas under a burst of H-FIRE pulses (1-1-1-1 μs, 440 V/cm), the AP peak decreased to 13.05 mV (by 5.33 mV) and was delayed to t = 26.82 ms. Further analysis revealed that both IRE and H-FIRE stimulation have an optimal electric field window: moderate increases in field strength enhanced excitability, while excessive intensity caused inhibitory effects due to over-electroporation. In addition, prolonging the inter-phase delay, inter-pulse delay, and pulse width of H-FIRE pulses aggravated EP effects and significantly suppressed excitability. Compared with the classical HH model, the proposed model more accurately reflects neuronal excitability under high electric fields and has important implications for the study of single-neuron stimulation.