Cellular excitability and ns-pulsed electric fields : potential involvement of lipid oxidation in the action potential activation

Rems, Lea (author), Rainot, Aurianne (author), Wiczew, Daniel (author), Szulc, Natalia (author), Tarek, Mounir (author)

Recent studies showed that nanosecond pulsed electric fields (nsPEFs) can activate voltage-gated ion channels (VGICs) and trigger action potentials (APs) in excitable cells. Under physiological conditions, VGICs’ activation takes place on time scales of the order 10–100 μs. These time scales are considerably longer than the applied pulse duration, thus activation of VGICs by nsPEFs remains puzzling and there is no clear consensus on the mechanisms involved. Here we propose that changes in local electrical properties of the cell membrane due to lipid oxidation might be implicated in AP activation. We first use MD simulations of model lipid bilayers with increasing concentration of primary and secondary lipid oxidation products and demonstrate that oxidation not only increases the bilayer conductance, but also the bilayer capacitance. Equipped with MD-based characterization of electrical properties of oxidized bilayers, we then resort to AP modelling at the cell level with Hodgkin-Huxley-type models. We confirm that a local change in membrane properties, particularly the increase in membrane conductance, due to formation of oxidized membrane lesions can be high enough to trigger an AP, even when no external stimulus is applied. However, excessive accumulation of oxidized lesions (or other conductive defects) can lead to altered cell excitability.

• Language: English
• Keywords: cell membrane, electroporation, lipid oxidation, molecular dynamics simulations, Hodgkin-Huxley models, voltage-gated ion channels
• Work type: Article
• Typology: 1.01 - Original Scientific Article
• Organization: FE - Faculty of Electrical Engineering
• Publication status: Published
• Publication version: Version of Record
• Year: 2024
• Number of pages: 14 str.
• Numbering: Vol. 155, art. 108588
• PID: 20.500.12556/RUL-152743
• UDC: 602.621
• ISSN on article: 1567-5394
• DOI: 10.1016/j.bioelechem.2023.108588
• COBISS.SI-ID: 169831427
• Publication date in RUL: 05.12.2023

Record is a part of a journal

• Title: Bioelectrochemistry
• Publisher: Elsevier
• ISSN: 1567-5394
• COBISS.SI-ID: 2502484

Licences

• License: CC BY-NC-ND 4.0, Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International
• Link: http://creativecommons.org/licenses/by-nc-nd/4.0/
• Description: The most restrictive Creative Commons license. This only allows people to download and share the work for no commercial gain and for no other purposes.

Secondary language

• Language: Slovenian
• Keywords: celična membrana, elektroporacija, oksidacija lipidov, simulacije molekularne dinamike, modeli tipa Hodgkin-Huxley, napetostni ionski kanali