Skip to main content

Electric Pulse Repetition Rate: Sensitization and Desensitization

  • Reference work entry
  • First Online:
Handbook of Electroporation

Abstract

In most applications of electroporation in biology, medicine, and industry, the desired effect is achieved by the delivery of multiple pulses. The pulse repetition rate (PRR) is one of the key factors which determine the efficiency of such treatments. Despite intense research, the impact of PRR has not been fully understood and remains one of the most controversial topics. Depending on the endpoints and specific conditions, increasing the PRR may increase, decrease, or make no difference in the effects of an electric pulse (EP) treatment. This complexity results from a combination of physical factors and biological effects. Electric modeling has been widely employed to explain PRR effects, but even the most advanced models showed limited predictive power. Recently it has been reported that mammalian cells exposed to electric pulses become more sensitive to subsequent EP treatments, a phenomenon that has been called electrosensitization. The sensitized state typically develops within tens of seconds after the initial EP exposure and reaches a maximum within minutes. When the overall EP treatments are made long enough for sensitization to develop, their effects increase two- to threefold. Electrosensitization is engaged when the overall treatment duration is made sufficiently long, by either lowering the PRR or by splitting the complete treatment into fractions. Understanding the role of PRR is critical for tuning various electroporation-based technologies and treatments to achieve the highest efficiency.

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 1,799.99
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Hardcover Book
USD 1,999.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

References

  • Al-Sakere B, Andre F, Bernat C, Connault E, Opolon P, Davalos RV, Rubinsky B, Mir LM (2007) Tumor ablation with irreversible electroporation. PLoS One 2(11):e1135

    Article  Google Scholar 

  • Bonnafous P, Vernhes M, Teissie J, Gabriel B (1999) The generation of reactive-oxygen species associated with long-lasting pulse-induced electropermeabilisation of mammalian cells is based on a non-destructive alteration of the plasma membrane. Biochim Biophys Acta 1461(1):123–134

    Article  Google Scholar 

  • Craviso GL, Choe S, Chatterjee I, Vernier PT (2012) Modulation of intracellular Ca2+ levels in chromaffin cells by nanoelectropulses. Bioelectrochemistry 87:244–252

    Article  Google Scholar 

  • Dermol J, Pakhomova ON, Pakhomov AG, Miklavcic D (2016) Cell electrosensitization exists only in certain electroporation buffers. PLoS One 11(7):e0159434

    Article  Google Scholar 

  • Faurie C, Rebersek M, Golzio M, Kanduser M, Escoffre JM, Pavlin M, Teissie J, Miklavcic D, Rols MP (2010) Electro-mediated gene transfer and expression are controlled by the life-time of DNA/membrane complex formation. J Gene Med 12(1):117–125

    Article  Google Scholar 

  • Gianulis EC, Pakhomov AG (2015) Gadolinium modifies the cell membrane to inhibit permeabilization by nanosecond electric pulses. Arch Biochem Biophys 570:1–7

    Article  Google Scholar 

  • Jiang N, Cooper BY (2011) Frequency-dependent interaction of ultrashort E-fields with nociceptor membranes and proteins. Bioelectromagnetics 32(2):148–163

    Article  Google Scholar 

  • Jiang C, Shao Q, Bischof J (2015) Pulse timing during irreversible electroporation achieves enhanced destruction in a hindlimb model of cancer. Ann Biomed Eng 43(4):887–895

    Article  Google Scholar 

  • Lamberti P, Romeo S, Sannino A, Zeni L, Zeni O (2015) The role of pulse repetition rate in nsPEF-induced electroporation: a biological and numerical investigation. IEEE Trans Biomed Eng 62(9):2234–2243

    Article  Google Scholar 

  • Marty M, Sersa G, Garbay JR, Gehl J, Collins CG, Snoj M, Billard V, Geertsen PF, Larkin JO, Miklavcic D, Pavlovic I, Paulin-Kosir SM, Cemazar M, Morsli N, Rudolf Z, Robert C, O’Sullivan GC, Mir LM (2006) Electrochemotherapy – an easy, highly effective and safe treatment of cutaneous and subcutaneous metastases: results of ESOPE (European Standard Operating Procedures of Electrochemotherapy) study. EJC Suppl 4(11):3–13

    Article  Google Scholar 

  • Muratori C, Pakhomov AG, Xiao S, Pakhomova ON (2016) Electrosensitization assists cell ablation by nanosecond pulsed electric field in 3D cultures. Sci Rep 6:23225

    Article  Google Scholar 

  • Nuccitelli R, Tran K, Sheikh S, Athos B, Kreis M, Nuccitelli P (2010) Optimized nanosecond pulsed electric field therapy can cause murine malignant melanomas to self-destruct with a single treatment. Int J Cancer 127(7):1727–1736

    Article  Google Scholar 

  • Pakhomova ON, Gregory BW, Khorokhorina VA, Bowman AM, Xiao S, Pakhomov AG (2011) Electroporation-induced electrosensitization. PLoS One 6(2):e17100

    Article  Google Scholar 

  • Pakhomova ON, Gregory BW, Pakhomov AG (2013) Facilitation of electroporative drug uptake and cell killing by electrosensitization. J Cell Mol Med 17(1):154–159

    Article  Google Scholar 

  • Pucihar G, Mir LM, Miklavcic D (2002) The effect of pulse repetition frequency on the uptake into electropermeabilized cells in vitro with possible applications in electrochemotherapy. Bioelectrochemistry 57(2):167–172

    Article  Google Scholar 

  • Rubinsky B (ed) (2010) Irreversible electroporation, Series in Biomedical Engineering. Springer, Berlin

    MATH  Google Scholar 

  • Schoenbach K, Joshi R, Beebe S, Baum C (2009) A scaling law for membrane permeabilization with nanopulses. IEEE Trans Dielectr Electr Insul 16(5):1224–1235

    Article  Google Scholar 

  • Sersa G, Kranjc S, Scancar J, Krzan M, Cemazar M (2010) Electrochemotherapy of mouse sarcoma tumors using electric pulse trains with repetition frequencies of 1 Hz and 5 kHz. J Membr Biol 236(1):155–162

    Article  Google Scholar 

  • Silve A, Guimera Brunet A, Al-Sakere B, Ivorra A, Mir LM (2014) Comparison of the effects of the repetition rate between microsecond and nanosecond pulses: electropermeabilization-induced electro-desensitization? Biochim Biophys Acta 1840(7):2139–2151

    Article  Google Scholar 

  • Son RS, Gowrishankar TR, Smith KC, Weaver JC (2016) Modeling a conventional electroporation pulse train: decreased pore number, cumulative calcium transport and an example of electrosensitization. IEEE Trans Biomed Eng 63(3):571–580

    Article  Google Scholar 

  • Steelman ZA, Tolstykh GP, Beier HT, Ibey BL (2016) Cellular response to high pulse repetition rate nanosecond pulses varies with fluorescent marker identity. Biochem Biophys Res Commun 478(3):1261–1267

    Article  Google Scholar 

  • Thompson GL, Roth C, Tolstykh G, Kuipers M, Ibey BL (2014) Disruption of the actin cortex contributes to susceptibility of mammalian cells to nanosecond pulsed electric fields. Bioelectromagnetics 35(4):262–272

    Article  Google Scholar 

  • Vernhes M-C, Cabanes P-A, Teissie J (1999) Chinese hamster ovary cells sensitivity to localized electrical stresses. Bioelectrochem Bioenerg 48:17–25

    Article  Google Scholar 

  • Vernier PT, Sun Y, Gundersen MA (2006) Nanoelectropulse-driven membrane perturbation and small molecule permeabilization. BMC Cell Biol 7:37

    Article  Google Scholar 

  • Vernier PT, Levine ZA, Wu YH, Joubert V, Ziegler MJ, Mir LM, Tieleman DP (2009) Electroporating fields target oxidatively damaged areas in the cell membrane. PLoS One 4(11):e7966

    Article  Google Scholar 

  • Yang X-J, Li J, Sun C-X, Zheng F-Y, Hu L-N (2009) The effect of high frequency steep pulsed electric fields on in vitro and in vivo antitumor efficiency of ovarian cancer cell line skov3 and potential use in electrochemotherapy. J Exp Clin Cancer Res 28(1):53

    Article  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Olga Pakhomova .

Editor information

Editors and Affiliations

Rights and permissions

Reprints and permissions

Copyright information

© 2017 Springer International Publishing AG

About this entry

Cite this entry

Muratori, C., Casciola, M., Pakhomova, O. (2017). Electric Pulse Repetition Rate: Sensitization and Desensitization. In: Miklavčič, D. (eds) Handbook of Electroporation. Springer, Cham. https://doi.org/10.1007/978-3-319-32886-7_23

Download citation

Publish with us

Policies and ethics