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

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

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.

• Jezik: Angleški jezik
• Ključne besede: cell membrane, electroporation, lipid oxidation, molecular dynamics simulations, Hodgkin-Huxley models, voltage-gated ion channels
• Vrsta gradiva: Članek v reviji
• Tipologija: 1.01 - Izvirni znanstveni članek
• Organizacija: FE - Fakulteta za elektrotehniko
• Status publikacije: Objavljeno
• Različica publikacije: Objavljena publikacija
• Leto izida: 2024
• Št. strani: 14 str.
• Številčenje: Vol. 155, art. 108588
• PID: 20.500.12556/RUL-152743
• UDK: 602.621
• ISSN pri članku: 1567-5394
• DOI: 10.1016/j.bioelechem.2023.108588
• COBISS.SI-ID: 169831427
• Datum objave v RUL: 05.12.2023

Gradivo je del revije

• Naslov: Bioelectrochemistry
• Založnik: Elsevier
• ISSN: 1567-5394
• COBISS.SI-ID: 2502484

Licence

• Licenca: CC BY-NC-ND 4.0, Creative Commons Priznanje avtorstva-Nekomercialno-Brez predelav 4.0 Mednarodna
• Povezava: http://creativecommons.org/licenses/by-nc-nd/4.0/deed.sl
• Opis: Najbolj omejujoča licenca Creative Commons. Uporabniki lahko prenesejo in delijo delo v nekomercialne namene in ga ne smejo uporabiti za nobene druge namene.

Sekundarni jezik

• Jezik: Slovenski jezik
• Ključne besede: celična membrana, elektroporacija, oksidacija lipidov, simulacije molekularne dinamike, modeli tipa Hodgkin-Huxley, napetostni ionski kanali