The experimental results guided the development of computational models describing the effects of electroporation on changes in transmembrane voltage in non-excitable and excitable cells. The models revealed that even a small increase in nonselective ionic current associated with electroporation can lead to complete depolarization of the membrane. We found that under typical electroporation conditions, the nonselective leak current is sufficiently high to render the transmembrane voltage unaffected by ion channel modulators. However, during the membrane resealing phase, activation of ion channels was observed to contribute to changes in transmembrane voltage. Additionally, experiments were conducted to assess the potential use of ion channel modulators in influencing cell susceptibility to electroporation treatment. The original plan was to test ion channel modulators that influence the extent and longevity of membrane depolarization following electroporation; however, we found that optical measurements of transmembrane voltage became unreliable when approaching conditions of irreversible electroporation and cell death. We instead tested the sodium channel inhibitor lidocaine, which is generally used for local anesthesia in electroporation treatments. The results indicate that lidocaine potentiated cell death, but this effect was primarily attributed to the cytotoxicity of lidocaine itself, with minimal synergistic effects with electroporation. In addition to the scientific work, the researcher gained new expertise in experimental and theoretical methodologies, acquired new teaching experience and experience in independent supervision of BSc, MSc, and PhD students, and secured an ERC Starting Grant that will continue and expands the research initiated during the project. Consequently, the project significantly contributed to the researcher’s academic career development as an independent principal investigator.
