Safety factor for electrostimulation with nanosecond pulses

Abstract

While electrical stimulation with pulses of milli- or microsecond duration is possible without electroporation, stimulation with nanosecond pulses typically entails electroporation, and nanosecond pulses can even cause electroporation without stimulation. A recently proposed explanation for this intriguing finding is that stimulation requires not only that a threshold membrane potential is reached, but also that it is sustained for a certain time tmin, while electroporation occurs almost immediately after a higher threshold potential is reached. Here we analytically derive stimulation and electroporation thresholds for membranes that satisfy these assumptions. We analyze the safety factor, i.e. the ratio between electroporation and stimulation threshold and its dependence on pulse duration, membrane charging time constant, and tmin. We find that the safety factor is sharply reduced if both the pulse duration and the membrane charging time constant are below tmin. We discuss different approaches to get models with varying tmin that could be used to experimentally test this theory and cardiac applications.