ID: 2213

• Title:
  Comparison of the Thresholds for Electroporation and Excitation for Pulses within Nanosecond–Millisecond duration range
  
  Authors:
  

  Saulis, Gintautas - Vytautas Magnus University, Kaunas, Lithuania
  Silkunas, Mantas - Old Dominion University, Norfolk, VA, USA
  Saule, Rita - Vytautas Magnus University, Kaunas, Lithuania

  
  
  Abstract:
  Exposure of cells with pulses to strong electric field can cause permeabilization of the cell plasma membrane (electroporation), stimulation of excitable cells, or both [1]. In some applications, e.g. non-thermal ablation of cardiac or tumour tissue with irreversible electroporation, excitation of muscle cells is not desirable [1], while in other ones, it would be better to avoid electroporation [2].
  
  Theoretical analysis and experimental data obtained up to date show that, depending on the membrane charging time constant, pulse strength and duration, the complex interplay of excitation and electroporation can be observed [2]. Excitation with or without damaging of the cell plasma membrane due to electroporation can be achieved.
  
  However, while carrying theoretical analysis [2,3], some minor simplifications were used. Meanwhile, these simplifications might be important for the detailed comparison of electroporation and excitation thresholds as for some pulse durations these thresholds are close to each other. The aim of this study was to analyse theoretically the dependence of the threshold for electroporation in more details within a wide range of pulse durations (nanoseconds–milliseconds) and compare the results with experimental data on excitation of neurons obtained earlier [4].
  
  Electroporation of mouse hepatoma MH-22A cells was determined from the increase of the plasma membrane permeability to potassium ions [5]. It was assumed that the threshold of electroporation corresponds to the formation of at least one pore. Theoretical dependences of the threshold of electroporation of a neuron on pulse duration was calculated on the basis of the mechanism of electroporation [6]. Parameters required for the calculation were estimated from the experimental data obtained in mouse hepatoma MH-22A and Chinese hamster ovary cells. For the comparison with experimental data, the dependence of the threshold for excitation of dissociated E18 rat hippocampal neurons, determined for single square-wave electric pulses with the durations from 100 ns to 1 ms, obtained earlier [4] was used.
  
  The experimental excitation-duration curve can be approximated by the straight line in a log-log plot. The slope of this line is equal to -0.5 and remains the same for all range of pulse durations studied (from 100 ns to 1 ms). Meanwhile, the slope of the dependence of the electric field strength required to electroporate the cell on the pulse duration varies from -0.06 to -0.9 for different ranges of pulse durations.
  
  From this analysis, it can be concluded that the results of the exposure of neurons by a single square-wave pulse depend strongly on its duration:
  
  1) For pulses longer than 10–20 us the threshold for neuron excitation is much lower than that for electroporation.
  
  2) Pulses with the durations from 200–300 ns to 10–20 us, which cause neuron excitation, should electroporate them as well.
  
  3) Threshold for excitation becomes close to or even lower than the threshold for electroporation for pulses shorter than 200–300 ns.
  
  
  
  Keywords:
  Electroporation, excitation, neuron, Chinese hamster ovary cells, kinetics of pore formation, pulse duration
  
  Refs:
  [1] M. Casciola, T.K. Feaster, M.J. Caiola, D. Keck, K. Blinova, Front. Physiol. 13 (2022) 1064168. [2] A.G. Pakhomov, O.N. Pakhomova, Bioelectrochemistry 136 (2020) 107598. [3] C.W. Zemlin, Bioelectrochemistry 141 (2021) 107882. [4] M. Silkunas, E. Gudvangen, V. Novickij, A.G. Pakhomov, Biochim. Biophys. Acta 1864 (2022) 184034. [5] G. Saulis, R. Praneviciute, Anal. Biochem. 345 (2005) 340-342. [6] G. Saulis, Food Eng. Rev. 2 (2010) 52-73.
  
  Topic 1:
  3. Modelling and simulation of exposures and effects
  
  Topic 2:
  1. Biological responses (molecular, subcellular, cellular and intercellular)