scholarly journals Beyond voltage-gated ion channels: Voltage-operated membrane proteins and cellular processes

2018 ◽  
Vol 233 (10) ◽  
pp. 6377-6385 ◽  
Author(s):  
Jianping Zhang ◽  
Xingjuan Chen ◽  
Yucong Xue ◽  
Nikita Gamper ◽  
Xuan Zhang
Keyword(s):  
Ion Channels ◽  
Membrane Proteins ◽  
Voltage Gated ◽  
Cellular Processes ◽  
Voltage Gated Ion Channels ◽  
Gated Ion Channels

scholarly journals Molecular basis for voltage sensitivity in membrane proteins

2018 ◽  
Author(s):  
Marina A. Kasimova ◽  
Erik Lindahl ◽  
Lucie Delemotte
Keyword(s):  
Membrane Potential ◽  
Ion Channels ◽  
Membrane Proteins ◽  
Voltage Sensitivity ◽  
Voltage Sensing ◽  
Suggested Approach ◽  
Voltage Gated ◽  
Living Organisms ◽  
Voltage Gated Ion Channels ◽  
Gated Ion Channels

ABSTRACTVoltage-sensitive membrane proteins are united by the ability to transform changes in the membrane potential into mechanical work. They are responsible for a spectrum of key physiological processes in living organisms, including electric signaling and progression along the cell cycle. While the voltage-sensing mechanism has been well characterized for some membrane proteins such as voltage-gated ion channels, for others even the location of the voltage-sensing elements remains unknown. The detection of these elements using experimental techniques is complicated due to the large diversity of membrane proteins. Here, we suggest a computational approach to predict voltage-sensing elements in any membrane protein independent of structure or function. It relies on the estimation of the capacity of a protein to respond to changes in the membrane potential. We first show how this property correlates well with voltage sensitivity by applying our approach to a set of membrane proteins including voltage-sensitive and voltage-insensitive ones. We further show that it correctly identifies true voltage-sensitive residues in the voltage sensor domain of voltage-gated ion channels. Finally, we investigate six membrane proteins for which the voltage-sensing elements have not yet been characterized and identify residues and ions potentially involved in the response to voltage. The suggested approach is fast and simple and allows for characterization of voltage sensitivity that goes beyond mere identification of charges. We anticipate that its application prior to mutagenesis experiments will allow for significant reduction of the number of potential voltage-sensitive elements to be tested.

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 Determining the molecular basis of voltage sensitivity in membrane proteins

2018 ◽  
Vol 150 (10) ◽  
pp. 1444-1458 ◽  
Author(s):  
Marina A. Kasimova ◽  
Erik Lindahl ◽  
Lucie Delemotte
Keyword(s):  
Membrane Potential ◽  
Ion Channels ◽  
Membrane Proteins ◽  
Cell Cycle Progression ◽  
Voltage Sensitivity ◽  
Voltage Sensing ◽  
Suggested Approach ◽  
Voltage Gated ◽  
Voltage Gated Ion Channels ◽  
Gated Ion Channels

Voltage-sensitive membrane proteins are united by their ability to transform changes in membrane potential into mechanical work. They are responsible for a spectrum of physiological processes in living organisms, including electrical signaling and cell-cycle progression. Although the mechanism of voltage-sensing has been well characterized for some membrane proteins, including voltage-gated ion channels, even the location of the voltage-sensing elements remains unknown for others. Moreover, the detection of these elements by using experimental techniques is challenging because of the diversity of membrane proteins. Here, we provide a computational approach to predict voltage-sensing elements in any membrane protein, independent of its structure or function. It relies on an estimation of the propensity of a protein to respond to changes in membrane potential. We first show that this property correlates well with voltage sensitivity by applying our approach to a set of voltage-sensitive and voltage-insensitive membrane proteins. We further show that it correctly identifies authentic voltage-sensitive residues in the voltage-sensor domain of voltage-gated ion channels. Finally, we investigate six membrane proteins for which the voltage-sensing elements have not yet been characterized and identify residues and ions that might be involved in the response to voltage. The suggested approach is fast and simple and enables a characterization of voltage sensitivity that goes beyond mere identification of charges. We anticipate that its application before mutagenesis experiments will significantly reduce the number of potential voltage-sensitive elements to be tested.

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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