title: Diffuse, non-polar electropermeabilization and reduced propidium uptake distinguish the effect of nanosecond electric pulses.
abstract: Ca2+ activation and membrane electroporation by 10-ns and 4-ms electric pulses (nsEP and msEP) were compared in rat embryonic cardiomyocytes. The lowest electric field which triggered Ca2+ transients was expectedly higher for nsEP (36 kV/cm) than for msEP (0.09 kV/cm) but the respective doses were similar (190 and 460 mJ/g). At higher intensities, both stimuli triggered prolonged firing in quiescent cells. An increase of basal Ca2+ level by >10 nM in cells with blocked voltage-gated Ca2+ channels and depleted Ca2+ depot occurred at 63 kV/cm (nsEP) or 0.14 kV/cm (msEP) and was regarded as electroporation threshold. These electric field values were at 150-230% of stimulation thresholds for both msEP and nsEP, notwithstanding a 400,000-fold difference in pulse duration. For comparable levels of electroporative Ca2+ uptake, msEP caused at least 10-fold greater uptake of propidium than nsEP, suggesting increased yield of larger pores. Electroporation by msEP started Ca2+ entry abruptly and locally at the electrode-facing poles of cell, followed by a slow diffusion to the center. In a stark contrast, nsEP evoked a "supra-electroporation" pattern of slower but spatially uniform Ca2+ entry. Thus nsEP and msEP had comparable dose efficiency, but differed profoundly in the size and localization of electropores.
authors.affiliation: Frank Reidy Research Center for Bioelectrics, Old Dominion University, Norfolk, VA 23508, USA.
authors.forename: Iurii
authors.initials: I
authors.lastname: Semenov
authors.affiliation: Frank Reidy Research Center for Bioelectrics, Old Dominion University, Norfolk, VA 23508, USA; Department of Electrical and Computer Engineering, Old Dominion University, Norfolk, VA 23508, USA.
authors.forename: Christian
authors.initials: C
authors.lastname: Zemlin
authors.affiliation: Frank Reidy Research Center for Bioelectrics, Old Dominion University, Norfolk, VA 23508, USA.
authors.forename: Olga N
authors.initials: ON
authors.lastname: Pakhomova
authors.affiliation: Frank Reidy Research Center for Bioelectrics, Old Dominion University, Norfolk, VA 23508, USA; Department of Electrical and Computer Engineering, Old Dominion University, Norfolk, VA 23508, USA.
authors.forename: Shu
authors.initials: S
authors.lastname: Xiao
authors.affiliation: Frank Reidy Research Center for Bioelectrics, Old Dominion University, Norfolk, VA 23508, USA. Electronic address: apakhomo@odu.edu.
authors.forename: Andrei G
authors.initials: AG
authors.lastname: Pakhomov
mesh_terms: D000818:Animals; D002463:Cell Membrane Permeability / Q000502:physiology* / Q000528:radiation effects; D002478:Cells, Cultured; D004307:Dose-Response Relationship, Radiation; D018274:Electroporation / Q000379:methods*; D008657:Metabolic Clearance Rate / Q000528:radiation effects; D032383:Myocytes, Cardiac / Q000502:physiology* / Q000528:radiation effects*; D011419:Propidium / Q000493:pharmacokinetics*; D011829:Radiation Dosage; D051381:Rats; D055672:Static Electricity
chemical_list: D011419:Propidium
keywords: Calcium activation; Cardiomyocytes; Electropermeabilization; Electroporation; Nanosecond electric pulses