Bioelectricty of Cancer: Voltage-Gated Ion Channels and Direct-Current Electric Fields

2016 ◽  
pp. 281-306
Keyword(s):  
Ion Channels ◽  
Electric Fields ◽  
Direct Current ◽  
Voltage Gated ◽  
Voltage Gated Ion Channels ◽  
Gated Ion Channels

scholarly journals Pulsed electric fields create pores in the voltage sensors of voltage-gated ion channels

2019 ◽  
Author(s):  
L. Rems ◽  
M. A. Kasimova ◽  
I. Testa ◽  
L. Delemotte
Keyword(s):  
Ion Channels ◽  
Membrane Proteins ◽  
Membrane Permeability ◽  
Electric Fields ◽  
Molecular Mechanisms ◽  
Pulsed Electric Fields ◽  
Pulse Treatment ◽  
Voltage Gated ◽  
Voltage Gated Ion Channels ◽  
Gated Ion Channels

AbstractPulsed electric fields are increasingly used in medicine to transiently increase the cell membrane permeability via electroporation, in order to deliver therapeutic molecules into the cell. One type of events that contributes to this increase in membrane permeability is the formation of pores in the membrane lipid bilayer. However, electrophysiological measurements suggest that membrane proteins are affected as well, particularly voltage-gated ion channels (VGICs). The molecular mechanisms by which the electric field could affects these molecules remain unidentified. In this study we used molecular dynamics (MD) simulations to unravel the molecular events that take place in different VGICs when exposing them to electric fields mimicking electroporation conditions. We show that electric fields induce pores in the voltage-sensor domains (VSDs) of different VGICs, and that these pores form more easily in some channels than in others. We demonstrate that poration is more likely in VSDs that are more hydrated and are electrostatically more favorable for the entry of ions. We further show that pores in VSDs can expand into so-called complex pores, which become stabilized by lipid head-groups. Our results suggest that such complex pores are considerably more stable than conventional lipid pores and their formation can lead to severe unfolding of VSDs from the channel. We anticipate that such VSDs become dysfunctional and unable to respond to changes in transmembrane voltage, which is in agreement with previous electrophyiological measurements showing a decrease in the voltage-dependent transmembrane ionic currents following pulse treatment. Finally, we discuss the possibility of activation of VGICs by submicrosecond-duration pulses. Overall our study reveals a new mechanism of electroporation through membranes containing voltage-gated ion channels.Statement of SignificancePulsed electric fields are often used for treatment of excitable cells, e.g., for gene delivery into skeletal muscles, ablation of the heart muscle or brain tumors. Voltage-gated ion channels (VGICs) underlie generation and propagation of action potentials in these cells, and consequently are essential for their proper function. Our study reveals the molecular mechanisms by which pulsed electric fields directly affect VGICs and addresses questions that have been previously opened by electrophysiologists. We analyze VGICs’ characteristics, which make them prone for electroporation, including hydration and electrostatic properties. This analysis is easily transferable to other membrane proteins thus opening directions for future investigations. Finally, we propose a mechanism for long-lived membrane permeability following pulse treatment, which to date remains poorly understood.

scholarly journals Cellular defibrillation: interaction of micro-scale electric fields with voltage-gated ion channels

2015 ◽  
Vol 41 (4) ◽  
pp. 421-431 ◽  
Author(s):  
Armin Kargol ◽  
Leszek Malkinski ◽  
Rahmatollah Eskandari ◽  
Maya Carter ◽  
Daniel Livingston
Keyword(s):  
Ion Channels ◽  
Electric Fields ◽  
Voltage Gated ◽  
Micro Scale ◽  
Voltage Gated Ion Channels ◽  
Gated Ion Channels

scholarly journals Pulsed Electric Fields Can Create Pores in the Voltage Sensors of Voltage-Gated Ion Channels

2020 ◽  
Vol 119 (1) ◽  
pp. 190-205 ◽  
Author(s):  
Lea Rems ◽  
Marina A. Kasimova ◽  
Ilaria Testa ◽  
Lucie Delemotte
Keyword(s):  
Ion Channels ◽  
Electric Fields ◽  
Pulsed Electric Fields ◽  
Voltage Sensors ◽  
Voltage Gated ◽  
Voltage Gated Ion Channels ◽  
Gated Ion Channels

Voltage-Gated Ion Channels, New Targets in Anti-Cancer Research

2007 ◽  
Vol 2 (3) ◽  
pp. 189-202 ◽  
Author(s):  
Le Jean-Yves ◽  
Ouadid-Ahidouch Halima ◽  
Soriani Olivier ◽  
Besson Pierre ◽  
Ahidouch Ahmed ◽  
...  
Keyword(s):  
Cancer Research ◽  
Ion Channels ◽  
Voltage Gated ◽  
New Targets ◽  
Anti Cancer ◽  
Voltage Gated Ion Channels ◽  
Gated Ion Channels

scholarly journals Expression and Distribution of Voltage Gated Ion Channels in Ferret SA Node

2009 ◽  
Vol 96 (3) ◽  
pp. 261a
Author(s):  
Muugu V. Brahmajothi ◽  
Michael. J. Morales ◽  
Donald L. Campbell ◽  
Charles Steenbergen ◽  
Harold C. Strauss
Keyword(s):  
Ion Channels ◽  
Voltage Gated ◽  
Sa Node ◽  
Voltage Gated Ion Channels ◽  
Gated Ion Channels
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