scholarly journals Membrane Potential-Dependent Inactivation of Voltage-Gated Ion Channels in  -Cells Inhibits Glucagon Secretion From Human Islets

Diabetes ◽  
2010 ◽  
Vol 59 (9) ◽  
pp. 2198-2208 ◽  
Author(s):  
R. Ramracheya ◽  
C. Ward ◽  
M. Shigeto ◽  
J. N. Walker ◽  
S. Amisten ◽  
...  
Keyword(s):  
Membrane Potential ◽  
Ion Channels ◽  
Glucagon Secretion ◽  
Human Islets ◽  
Voltage Gated ◽  
Dependent Inactivation ◽  
Voltage Gated Ion Channels ◽  
In Cells ◽  
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 Fluorescence Imaging of Electrically Stimulated Cells

2003 ◽  
Vol 8 (6) ◽  
pp. 660-667 ◽  
Author(s):  
Paul Burnett ◽  
Janet K. Robertson ◽  
Jeffrey M. Palmer ◽  
Richard R. Ryan ◽  
Adrienne E. Dubin ◽  
...  
Keyword(s):  
Membrane Potential ◽  
Ion Channels ◽  
Ion Channel ◽  
High Throughput ◽  
Pharmacological Intervention ◽  
Voltage Gradient ◽  
Channel Activity ◽  
Voltage Gated ◽  
Voltage Gated Ion Channels ◽  
Gated Ion Channels

Designing high-throughput screens for voltage-gated ion channels has been a tremendous challenge for the pharmaceutical industry because channel activity is dependent on the transmembrane voltage gradient, a stimulus unlike ligand binding to G-protein-coupled receptors or ligand-gated ion channels. To achieve an acceptable throughput, assays to screen for voltage-gated ion channel modulators that are employed today rely on pharmacological intervention to activate these channels. These interventions can introduce artifacts. Ideally, a high-throughput screen should not compromise physiological relevance. Hence, a more appropriate method would activate voltage-gated ion channels by altering plasma membrane potential directly, via electrical stimulation, while simultaneously recordingthe operation of the channel in populations of cells. The authors present preliminary results obtained from a device that is designed to supply precise and reproducible electrical stimuli to populations of cells. Changes in voltage-gated ion channel activity were monitored using a digital fluorescent microscope. The prototype electric field stimulation (EFS) device provided real-time analysis of cellular responsiveness to physiological and pharmacological stimuli. Voltage stimuli applied to SK-N-SH neuroblastoma cells cultured on the EFS device evoked membrane potential changes that were dependent on activation of voltage-gated sodium channels. Data obtained using digital fluorescence microscopy suggests suitability of this system for HTS.

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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