Cancellation of nerve excitation by the reversal of nanosecond stimulus polarity and its relevance to the gating time of sodium channels

Casciola, Maura; Xiao, Shu; Apollonio, Francesca; Paffi, Alessandra; Liberti, Micaela; Muratori, Claudia; Pakhomov, Andrei G.

doi:10.1007/s00018-019-03126-0

Cited by 35 publications

(30 citation statements)

References 57 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…In cells, the transport of small molecules caused by a unipolar pulse can be attenuated or cancelled by a closely following pulse of opposite polarity. 28,29,[42][43][44][45][46][47] In other words, a unipolar pulse is more effective in causing small molecule transport into cells than a bipolar pulse of double the duration. 2 ns unipolar pulses and bipolar pulses applied to GUV with no interpulse delay (negative pulse immediately follows the positive pulse without any intervening interval of time) results in equal transport of calcein, whereas a short delay of 50 ns between the bipolar pulse phases results in twice the transport (Fig.…”

Section: Main Textmentioning

confidence: 99%

Dye Transport through Bilayers Agrees with Lipid Electropore Molecular Dynamics

Sözer

Haldar

Blank

et al. 2020

Biophysical Journal

View full text Add to dashboard Cite

Delivery of molecules to cells via electropermeabilization (electroporation) is a common procedure in laboratories and clinics. However, despite a long history of theoretical effort, electroporation protocols are still based on trial and error because the biomolecular structures and mechanisms underlying this phenomenon have not been established. Electroporation models, developed to explain observations of electrical breakdown of lipid membranes, describe the electric field-driven formation of pores in lipid bilayers. These transient pore models are consistent with molecular dynamics simulations, where field-stabilized lipid pores form within a few nanoseconds and collapse within tens of nanoseconds after the field is removed. Here we experimentally validate this nanoscale restructuring of bio-membranes by measuring the kinetics of transport of the impermeant fluorescent dye calcein into lipid vesicles exposed to ultrashort electric fields (6 ns and 2 ns), and by comparing these results to molecular simulations. Molecular transport after vesicle permeabilization induced by multiple pulses is additive for interpulse intervals as short as 50 ns, while the additive property of transport is no longer observed when the interval is reduced to 0 ns, consistent with the lifetimes of lipid electropores in molecular simulations. These results show that lipid vesicle responses to pulsed electric fields are significantly different from those of living cells where, for similar pulse properties, the uptake of fluorescent dye continues for several minutes.105 and is also made available for use under a CC0 license.

show abstract

Section: Main Textmentioning

confidence: 99%

Dye Transport through Bilayers Agrees with Lipid Electropore Molecular Dynamics

Sözer

Haldar

Blank

et al. 2020

Biophysical Journal

View full text Add to dashboard Cite

show abstract

“…This is analogous to the phenomenon of bipolar cancellation whereby the application of a second nanosecond pulse of opposite polarity can attenuate or abolish a cellular response (Ca 2+ transient, electronanoporation, fluorescent dye uptake, etc.) triggered by the corresponding unipolar pulse [25][26][27][28][29][30][31][32][33].…”

Section: Plos Onementioning

confidence: 99%

Paradoxical effects on voltage-gated Na+ conductance in adrenal chromaffin cells by twin vs single high intensity nanosecond electric pulses

et al. 2020

View full text Add to dashboard Cite

We previously reported that a single 5 ns high intensity electric pulse (NEP) caused an Efield-dependent decrease in peak inward voltage-gated Na + current (I Na) in isolated bovine adrenal chromaffin cells. This study explored the effects of a pair of 5 ns pulses on I Na recorded in the same cell type, and how varying the E-field amplitude and interval between the pulses altered its response. Regardless of the E-field strength (5 to 10 MV/m), twin NEPs having interpulse intervals � than 5 s caused the inhibition of TTX-sensitive I Na to approximately double relative to that produced by a single pulse. However, reducing the interval from 1 s to 10 ms between twin NEPs at E-fields of 5 and 8 MV/m but not 10 MV/m decreased the magnitude of the additive inhibitory effect by the second pulse in a pair on I Na. The enhanced inhibitory effects of twin vs single NEPs on I Na were not due to a shift in the voltage-dependence of steady-state activation and inactivation but were associated with a reduction in maximal Na + conductance. Paradoxically, reducing the interval between twin NEPs at 5 or 8 MV/m but not 10 MV/m led to a progressive interval-dependent recovery of I Na , which after 9 min exceeded the level of I Na reached following the application of a single NEP. Disrupting lipid rafts by depleting membrane cholesterol with methyl-β-cyclodextrin enhanced the inhibitory effects of twin NEPs on I Na and ablated the progressive recovery of this current at short twin pulse intervals, suggesting a complete dissociation of the inhibitory effects of twin NEPs on this current from their ability to stimulate its recovery. Our results suggest that in contrast to a single NEP, twin NEPs may influence membrane lipid rafts in a manner that enhances the trafficking of newly synthesized and/or recycling of endocytosed voltage-gated Na + channels, thereby pointing to novel means to regulate ion channels in excitable cells.

show abstract

“…In recent years, many studies have investigated the effects of bipolar pulses in the context of electroporation for biomedical applications. It was shown that bipolar pulses in the nanosecond range produce cancellation of the bioeffects classically observed when applying unipolar pulses [1]- [6]. This phenomenon was largely assessed with pulse durations from 60 ns [1], [3], [7] to 900 ns [8], and more recently for 2 ns [9], for different cell lines (CHO, Jurkat, U937, or excitable cells like chromaffin cells) and for a wide range of endpoints such as YO-PRO™-1 (YP) uptake, Ca 2+ transients, cell death, calcein efflux, nerve excitation, or phosphatidylserine externalization.…”

Section: Introductionmentioning

confidence: 99%

High-voltage 10 ns delayed paired or bipolar pulses for in vitro bioelectric experiments

Orlacchio

Carr

Palego

et al. 2021

Bioelectrochemistry

View full text Add to dashboard Cite

This is a PDF file of an article that has undergone enhancements after acceptance, such as the addition of a cover page and metadata, and formatting for readability, but it is not yet the definitive version of record. This version will undergo additional copyediting, typesetting and review before it is published in its final form, but we are providing this version to give early visibility of the article. Please note that, during the production process, errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain.

show abstract

Cancellation of nerve excitation by the reversal of nanosecond stimulus polarity and its relevance to the gating time of sodium channels

Cited by 35 publications

References 57 publications

Dye Transport through Bilayers Agrees with Lipid Electropore Molecular Dynamics

Dye Transport through Bilayers Agrees with Lipid Electropore Molecular Dynamics

Paradoxical effects on voltage-gated Na+ conductance in adrenal chromaffin cells by twin vs single high intensity nanosecond electric pulses

High-voltage 10 ns delayed paired or bipolar pulses for in vitro bioelectric experiments

Contact Info

Product

Resources

About