Changes in transmembrane voltage regulation due to cell electroporation

Blažič, Anja (author), Rems, Lea (mentor)

Electroporation enables the increase in cell membrane permeability by exposing cells to high-voltage electric pulses and is widely used in medical procedures such as electrochemotherapy, non-thermal tumour ablation, and most recently for ablation of arrhythmogenic cardiac tissue. Despite its broad applications, the regulation of transmembrane voltage following electroporation remains incompletely understood. This dissertation aims to investigate how TMV is shaped and modulated after electroporation, and how these changes influence downstream cellular processes. It builds on three complementary studies. The first study examined alterations in TMV over 30 min after pulse exposure, demonstrating that post-pulse TMV dynamics are governed by an interplay between nonselective leak current due to membrane permeabilization and ion channel activation. The second study examined reversible electroporation in patient-derived glioblastoma cells, showing that electric field exposure can alter the invasive behaviour of surviving cells, with evidence implicating ion channels in this adaptive response. The third study explored pharmacological inhibition of voltage-gated sodium channels using lidocaine during electroporation, revealing that lidocaine can affect cell survival outcome through mechanisms that extend beyond simple ion channel modulation. Taken together, these studies provide an integrated view of how electrical stress translates into functional and phenotypic cellular changes. By linking TMV regulation to ion channel activity, invasive behaviour, and pharmacological modulations, the findings extend the mechanistic understanding of electroporation and suggest novel opportunities for therapeutic modulation, particularly in the context of glioblastoma.

• Language: English
• Keywords: electroporation, transmembrane voltage changes, cell membrane permeability, cell survival, cell invasion, ion channels
• Work type: Doctoral dissertation
• Organization: BF - Biotechnical Faculty
• Year: 2025
• PID: 20.500.12556/RUL-177550
• Publication date in RUL: 24.12.2025

Secondary language

• Language: Slovenian
• Title: Spremembe v uravnavanju transmembranske napetosti po elektroporaciji celic

Abstract

Elektroporacija je pojav, pri katerem pride do povečane prepustnosti celične membrane zaradi izpostavitve celic visokonapetostnim električnim pulzom. Pogosto se uporablja v medicini, med drugim pri elektrokemoterapiji, netermični ablaciji tumorjev ter v zadnjem času tudi pri ablaciji aritmogenega srčnega tkiva. Kljub široki uporabi pa regulacija transmembranske napetosti po elektroporaciji ostaja nepopolno pojasnjena. Namen te disertacije je bil raziskati spremembe in mehanizme transmembranske napetosti po elektroporaciji ter ugotoviti, kako te spremembe vplivajo na nadaljnje celične procese. Delo temelji na treh medsebojno dopolnjujočih se študijah. V prvi študiji smo preučevali spremembe transmembranske napetosti v času 30 minut po izpostavitvi celic električnemu pulzu in pokazali, da dinamiko teh sprememb uravnava tako neselektivni tok ionov, ki nastane zaradi povečane prepustnosti membrane, kot tudi aktivacija ionskih kanalov. V drugi študiji smo ovrednotili vpliv reverzibilne elektroporacije na primarne humane glioblastomske celice ter pokazali spremembe v invazivnem vedenju preživelih celic, pri čemer je bilo nakazano, da so v te prilagoditvene odzive vključeni tudi ionski kanali.V tretji študiji pa smo raziskovali vpliv lidokaina, modulatorja napetostno odvisnih natrijevih kanalov, na elektroporacijo in pokazali, da lahko lidokain vpliva na preživetje celic prek mehanizmov, ki presegajo zgolj modulacijo ionskih kanalov. Skupaj rezultati teh študij ponujajo poglobljen vpogled v to, kako izpostavitev električnemu polju vpliva na spremembe v celičnih procesih in odzivu celic po elektroporaciji. Z razkrivanjem povezav med regulacijo transmembranske napetosti, delovanjem ionskih kanalov, invazivnostjo celic in farmakološko modulacijo odzivov na izpostavitev celic električnemu polju, ugotovitve v doktorski nalogi poglabljajo dosedanje razumevanje mehanizmov elektroporacije. S tem se odpirajo nove možnosti za terapevtsko modulacijo, zlasti pri zdravljenju glioblastoma.

• Keywords: elektroporacija, spremembe transmembranske napetosti, prepustnost plazemske membrane, preživetje celic, invazija celic, ionski kanali