Gadolinium Modifies the Cell Membrane to Inhibit Permeabilization by Nanosecond Electric Pulses

Authors

Elena C. Gianulis, Old Dominion University
Andrei G. Pakhomov, Old Dominion University

Document Type

Article

Publication Date

2015

Publication Title

Archives of Biochemistry and Biophysics

Volume

570

Pages

1-7

DOI

10.1016/j.abb.2015.02.013

Abstract

Lanthanide ions are the only known blockers of permeabilization by electric pulses of nanosecond duration (nsEP), but the underlying mechanisms are unknown. We employed timed applications of Gd³⁺ before or after nsEP (600-ns, 20 kV/cm) to investigate the mechanism of inhibition, and measured the uptake of the membrane-impermeable YO-PRO-1 (YP) and propidium (Pr) dyes. Gd³⁺ inhibited dye uptake in a concentration-dependent manner. The inhibition of Pr uptake was always about 2-fold stronger. Gd³⁺ was effective when added after nsEP, as well as when it was present during nsEP exposure and removed afterward. Pores formed by nsEP in the presence of Gd³⁺ remained quiescent unless Gd³⁺ was promptly washed away. Such pores resealed (or shrunk) shortly after the wash despite the absence of Gd³⁺. Finally, a brief (3 s) Gd³⁺ perfusion was equally potent at inhibiting dye uptake when performed either immediately before or after nsEP, or early before nsEP. The persistent protective effect of Gd³⁺ even in its absence proves that inhibition by Gd³⁺ does not result from simple pore obstruction. Instead, Gd³⁺ causes lasting modification of the membrane, occurring promptly and irrespective of pore presence; it makes the membrane less prone to permeabilization and/or reduces the stability of electropores.

Comments

NOTE: This is the author's pre-print version of a work that was published in Archives of Biochemistry and Biophysics. The final version was published as:

Gianulis, E. C., & Pakhomov, A. G. (2015). Gadolinium modifies the cell membrane to inhibit permeabilization by nanosecond electric pulses. Arch Biochem Biophys, 570, 1-7. doi:10.1016/j.abb.2015.02.013

Available at: http://dx.doi.org10.1016/j.abb.2015.02.013

Original Publication Citation

Gianulis, E. C., & Pakhomov, A. G. (2015). Gadolinium modifies the cell membrane to inhibit permeabilization by nanosecond electric pulses. Arch Biochem Biophys, 570, 1-7. doi:10.1016/j.abb.2015.02.013

Repository Citation

Gianulis, Elena C. and Pakhomov, Andrei G., "Gadolinium Modifies the Cell Membrane to Inhibit Permeabilization by Nanosecond Electric Pulses" (2015). Bioelectrics Publications. 157.
https://digitalcommons.odu.edu/bioelectrics_pubs/157

ORCID

Gianulis (0000-0001-5490-1822)