Conformational mobility of cationic voltage-gated ion channels
Olga S Sokolova1,2, Ekaterina Kravchuk2, Elizaveta Trifonova2
1Faculty of Biology, Shenzhen MSU-BIT University, Shenzhen, China.
Critical Reviews in Biochemistry and Molecular Biology
|June 10, 2026
Summary
Structural studies of voltage-gated ion channels reveal protein conformational changes during function. Advances in cryo-EM, NMR, and computational methods now allow detailed observation of these dynamic processes and lipid modulation.
Area of Science:
- Biochemistry
- Structural Biology
- Biophysics
Background:
- Ion channels are crucial membrane proteins, historically challenging to study structurally.
- Voltage-gated ion channels exhibit conformational changes essential for their function.
- Recent advancements in biochemical and computational methods have improved structural studies.
Purpose of the Study:
- To review structural studies of voltage-gated ion channel functioning and associated protein conformational changes.
- To highlight methodological advances enabling the observation of these dynamic processes.
- To discuss the role of lipid modulation and membrane mimetics in stabilizing ion channel conformations.
Main Methods:
- Cryo-electron microscopy (cryo-EM) and cryo-electron tomography for high-resolution structures.
- Nuclear Magnetic Resonance (NMR) spectroscopy for studying conformational dynamics.
- Molecular modeling and new algorithms for analyzing protein mobility and domain movements.
Main Results:
- Multiple models for ion channel activation mechanisms have been proposed based on experimental data.
- Specific functional states of ion channels can now be obtained and studied.
- Lipid interactions are critical for modulating ion channel function and conformation.
Conclusions:
- Modern structural biology techniques provide unprecedented insights into ion channel mechanisms.
- Understanding conformational dynamics is key to elucidating ion channel function.
- Lipid modulation plays a significant role in regulating ion channel activity.
Related Concept Videos
Voltage-gated Ion Channels
Voltage-gated ion channels are transmembrane proteins that open and close in response to changes in the membrane potential. They are present on the membranes of all electrically excitable cells such as neurons, heart, and muscle cells.
Generally, all voltage-gated ion channels have a 'voltage-sensing domain' that spans the lipid bilayer. The charged residues in the sensor move in response to the membrane potential changes that open the channel allowing ions movement. There are several types of...
Generally, all voltage-gated ion channels have a 'voltage-sensing domain' that spans the lipid bilayer. The charged residues in the sensor move in response to the membrane potential changes that open the channel allowing ions movement. There are several types of...
Voltage-gated Ion Channels
Voltage-gated ion channels are transmembrane proteins that open and close in response to changes in the membrane potential. They are present on the membranes of all electrically excitable cells such as neurons, heart, and muscle cells.
Generally, all voltage-gated ion channels have a 'voltage-sensing domain' that spans the lipid bilayer. The charged residues in the sensor move in response to the membrane potential changes that open the channel allowing ions movement. There are several types of...
Generally, all voltage-gated ion channels have a 'voltage-sensing domain' that spans the lipid bilayer. The charged residues in the sensor move in response to the membrane potential changes that open the channel allowing ions movement. There are several types of...
Non-gated Ion Channels
Ion channels are specialized proteins on the plasma membrane that allow charged ions to pass down their electrochemical gradient. Their main function is to maintain the membrane potential which is critical for cell viability. These channels are either gated or non-gated and can transport more than a thousand ions within milliseconds for the cellular event to occur.
Compared to the gated ion channels, the non-gated channels, also known as leakage or passive channels, have no gating mechanism.
Compared to the gated ion channels, the non-gated channels, also known as leakage or passive channels, have no gating mechanism.
Non-gated Ion Channels
Ion channels are specialized proteins on the plasma membrane that allow charged ions to pass down their electrochemical gradient. Their main function is to maintain the membrane potential which is critical for cell viability. These channels are either gated or non-gated and can transport more than a thousand ions within milliseconds for the cellular event to occur.
Compared to the gated ion channels, the non-gated channels, also known as leakage or passive channels, have no gating mechanism.
Compared to the gated ion channels, the non-gated channels, also known as leakage or passive channels, have no gating mechanism.
Mechanically-gated Ion Channels
Mechanically-gated ion channels are proteins found in eukaryotic and prokaryotic cell membranes that open in response to mechanical stress. Tension, compression, swelling, and shear stress can alter the conformation of the protein, opening a transmembrane channel that allows the passage of ions for signal transmission. In eukaryotes, mechanically-gated channels are distributed in several regions like the neurons, lungs, skin, bladder, and heart, where they play critical roles in numerous...
Mechanically-gated Ion Channels
Mechanically-gated ion channels are proteins found in eukaryotic and prokaryotic cell membranes that open in response to mechanical stress. Tension, compression, swelling, and shear stress can alter the conformation of the protein, opening a transmembrane channel that allows the passage of ions for signal transmission. In eukaryotes, mechanically-gated channels are distributed in several regions like the neurons, lungs, skin, bladder, and heart, where they play critical roles in numerous...


