Effects of electroporation on the function of sarco/endoplasmic reticulum ▫$Ca^{2+}$▫-ATPase and ▫$Na^+$▫,▫$K^+$▫-ATPase in H9c2 cells

Jan, Vid (author), Jusović, Maida (author), Miklavčič, Damijan (author)

Pulsed field ablation (PFA) is a promising new treatment for atrial fibrillation (AF), in which pulmonary vein isolation is achieved by irreversible electroporation. Electroporation causes ATP to leak through the permeabilized membrane. ATP is required both for the healing of the cell membrane and for the functioning of ion pumps, such as sarco/endoplasmic reticulum ▫$Ca^{2+}$▫-ATPase (SERCA) or ▫$Na^+$▫,▫$K^+$▫-ATPase (NKA), which play a key role in maintaining continuous contractions of the heart muscle. We investigated the effects of electroporation on the expression of ion pumps and possible correlations with the activation of AMPK, the main energy sensor in cells. H9c2 rat cardiac cells were exposed to either monopolar or bipolar (H-FIRE) pulses. Cells lysed 4 or 24 h after electroporation were used for mRNA and protein expression analyses. Overall, both pulse protocols caused a dosedependent downregulation of crucial SERCA and NKA isoforms, except for NKA▫$\alpha$▫2 and ▫$\beta$▫3, which were upregulated after 24 h. Monopolar pulses also decreased the phosphorylation of FXYD1, which may cause an inhibition of NKA activity. Both pulse protocols caused an increased AMPK activity, which may decrease both SERCA and NKA activity via calcium/calmodulin-dependent protein kinase. Our results provide important new insights into what happens in surviving cardiomyocytes after they are exposed to PFA.

• Language: English
• Keywords: irreversible electroporation, reversible electroporation, pulsed field ablation, sarco/endoplasmic reticulum Ca2+-ATPase, Na+, K+-ATPase, atrial fibrillation, AMPK activation, H-FIRE pulses, H9c2 cells
• 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: 21 str.
• Numbering: Vol. 14, iss. 7 [article no.] 2695
• PID: 20.500.12556/RUL-156319
• UDC: 602.621
• ISSN on article: 2076-3417
• DOI: 10.3390/app14072695
• COBISS.SI-ID: 190227203
• Publication date in RUL: 20.05.2024

Record is a part of a journal

• Title: Applied sciences
• Shortened title: Appl. sci.
• Publisher: MDPI
• ISSN: 2076-3417
• COBISS.SI-ID: 522979353

Licences

• License: CC BY 4.0, Creative Commons Attribution 4.0 International
• Link: http://creativecommons.org/licenses/by/4.0/
• Description: This is the standard Creative Commons license that gives others maximum freedom to do what they want with the work as long as they credit the author.

Secondary language

• Language: Slovenian
• Keywords: ireverzibilna ekektroporacija, reverzibilna elektroporacija, ablacija s pulznim električnim poljem, Ca2+-ATPaza sarko/endoplazemskega retikuluma, Na+, K+-ATPaza, atrijska fibrilacija, aktivacija AMPK, H-FIRE pulzi, celice H9c2

Projects

• Funder: ARIS - Slovenian Research and Innovation Agency
• Project number: P2-0249
• Name: Elektroporacija v biologiji, biotehnologiji in medicini

• Funder: ARIS - Slovenian Research and Innovation Agency
• Project number: I0-0022
• Name: Mreža raziskovalnih infrastrukturnih centrov Univerze v Ljubljani (MRIC UL)