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Controllable Ion Channel Expression through Inducible Transient Transfection
Published on: February 17, 2017
Voltage-gated ion channels and gating modifier toxins
William A Catterall1, Sandrine Cestèle, Vladimir Yarov-Yarovoy
1Department of Pharmacology, University of Washington, Seattle, WA 98195-7280, USA. wcatt@u.washington.edu
Summary
Voltage-gated ion channels, crucial for electrical signaling, are targeted by diverse neurotoxins. Understanding these toxin interactions, like voltage-sensor trapping, reveals common mechanisms across channel types.
Area of Science:
- Neuroscience
- Molecular Biology
- Biophysics
Background:
- Voltage-gated ion channels (sodium, calcium, potassium) are essential for nerve impulse generation and conduction.
- These channels share a common structure with six transmembrane segments and a pore loop.
- Neurotoxins interact with these channels at various sites, modulating their function.
Purpose of the Study:
- To explore the diverse mechanisms by which neurotoxins affect voltage-gated ion channels.
- To elucidate the structural basis of toxin interactions with channel proteins.
- To identify common modes of action for different classes of toxins.
Main Methods:
- Analysis of channel structure and function.
- Review of known neurotoxin interactions with ion channels.
- Molecular modeling of toxin-channel complexes (e.g., beta-scorpion toxin).
Main Results:
- Neurotoxins exhibit diverse actions, including pore block and modulation of voltage-dependent gating.
- Hydrophobic toxins can allosterically alter gating, while polypeptide toxins may use voltage-sensor trapping.
- Atomic-level modeling revealed the voltage-sensor trapping mechanism for a beta-scorpion toxin.
Conclusions:
- Neurotoxins provide valuable tools for studying ion channel function.
- Voltage-sensor trapping represents a potential common mechanism for polypeptide toxins acting on various voltage-gated ion channels.
- Understanding these interactions aids in the development of novel therapeutics and research probes.
Related Concept Videos
01:26Voltage-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...
01:26Voltage-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...
01:24Non-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.
01:24Non-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.
01:30Ligand-Gated Ion Channel Receptor: Gating Mechanism
Ligand-gated ion channels are transmembrane proteins that play a vital role in intercellular communication and functions of the nervous system. They allow the influx of ions across the membrane once the neurotransmitter binds, allowing the subsequent transmission of electrical excitation across the neurons. Other ligand-gated ion channels, like the γ-aminobutyric acid (GABA) receptor, permit anions like chloride into the cells on the binding of the GABA molecule. Their entry into the cell...
01:19Ion Channels
The movement of ions like sodium, potassium, and calcium into and out of the cell is essential to maintain the electrochemical gradient in living cells. The ion channels—a class of membrane transport proteins—help maintain this ionic gradient for the smooth functioning of physiological activities such as maintaining cell size and volume, conducting nerve impulses, and gas and nutrient exchange.
Ion channels are specialized integral membrane proteins on the plasma membrane that allow specific...
Ion channels are specialized integral membrane proteins on the plasma membrane that allow specific...