Plasma membrane depolarization and permeabilization due to electric pulses in cell lines of different excitability

In electroporation-based medical treatments, excitable tissues are treated, either intentionally (irreversible electroporation of brain cancer, gene electrotransfer or ablation of the heart muscle, gene electrotransfer of skeletal muscles), or unintentionally (excitable tissues near the target area). We investigated how excitable and non-excitable cells respond to electric pulses, and if electroporation could be an effective treatment of the tumours of the central nervous system. For three non-excitable and one excitable cell line, we determined a strength-duration curve for a single pulse of 10ns-10ms. The threshold for depolarization decreased with longer pulses and was higher for excitable cells. We modelled the response with the Lapicque curve and the Hodgkin-Huxley model. At 1μs a plateau of excitability was reached which could explain why high-frequency irreversible electroporation (H-FIRE) electroporates but does not excite cells. We exposed cells to standard electrochemotherapy parameters (8×100μs pulses, 1Hz, different voltages). Cells behaved similarly which indicates that electroporation most probably occurs at the level of lipid bilayer, independently of the voltage-gated channels. These results could be used for optimization of electric pulses to achieve maximal permeabilization and minimal excitation/pain sensation. In the future, it should be established whether the in vitro depolarization correlates to nerve/muscle stimulation and pain sensation in vivo.