Ruiz-Fernández, A.R.; Campos, L.; Villanelo, F.; Garate, J.A.; Perez-Acle, T. Protein-Mediated Electroporation in a Cardiac Voltage-Sensing Domain Due to an nsPEF Stimulus. Int. J. Mol. Sci.2023, 24, 11397.
Ruiz-Fernández, A.R.; Campos, L.; Villanelo, F.; Garate, J.A.; Perez-Acle, T. Protein-Mediated Electroporation in a Cardiac Voltage-Sensing Domain Due to an nsPEF Stimulus. Int. J. Mol. Sci. 2023, 24, 11397.
Ruiz-Fernández, A.R.; Campos, L.; Villanelo, F.; Garate, J.A.; Perez-Acle, T. Protein-Mediated Electroporation in a Cardiac Voltage-Sensing Domain Due to an nsPEF Stimulus. Int. J. Mol. Sci.2023, 24, 11397.
Ruiz-Fernández, A.R.; Campos, L.; Villanelo, F.; Garate, J.A.; Perez-Acle, T. Protein-Mediated Electroporation in a Cardiac Voltage-Sensing Domain Due to an nsPEF Stimulus. Int. J. Mol. Sci. 2023, 24, 11397.
Abstract
The Nanosecond Pulsed Electric Field (nsPEF) or Nano Pulsed Stimulation (NPS) is a cutting-edge technology that applies a series of high-voltage electric field pulses of extremely short duration, typically on the order of nanoseconds, to cells. This technique induces the formation of nanopores and activate ionic channels, thereby altering cellular activity. Recent simulations suggest that nsPEF also triggers a novel phenomenon, Protein-mediated Electroporation, whereby pores are formed through the voltage-sensing domain of ionic channels. In this study, we employed Molecular Dynamics simulations and machine learning techniques to investigate the Voltage Sensing Domain (VSD) of a cardiac channel under nsPEF stimulation. Specifically, we characterized VSD structures that form pores helping for the understanding of the physical chemistry underlying the defibrillation effect of nsPEF. Our analysis involved the clustering of 142 replicas simulated for 50 ns under the nsPEF stimulus. Subsequently, we identified the representative structures of each cluster and calculated the free energy between them. Our results demonstrate that although VSD structures are ubiquitous among ionic channels, they exhibit distinct responses to nsPEF stimuli. These findings have significant implications for the development of novel nsPEF-based therapies for cardiac diseases.
Computer Science and Mathematics, Artificial Intelligence and Machine Learning
Copyright:
This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
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