Related Experiment Video
Updated: Nov 11, 2025
12:26
Author Spotlight: Functional Site-Directed Fluorometry in Native Cells to Study Skeletal Muscle Excitability
Published on: June 2, 2023
1.2K
Structural determinants of voltage-gating properties in calcium channels
Monica L Fernández-Quintero1,2, Yousra El Ghaleb1, Petronel Tuluc3
1Department of Physiology and Medical Physics, Medical University Innsbruck, Innsbruck, Austria.
Elife
|March 30, 2021
Summary
Voltage-gated calcium channels (VGCCs) have distinct activation properties. Specific ion-pair formations in their voltage-sensing domains explain these unique gating characteristics.
Area of Science:
- Molecular and Cellular Neuroscience
- Biophysics
- Ion Channel Physiology
Background:
- Voltage-gated calcium channels (VGCCs) are crucial for excitable cell functions, including neuronal synaptic transmission and muscle contraction.
- Diverse VGCCs exhibit distinct voltage-dependent activation and kinetics, essential for their specialized roles.
Purpose of the Study:
- To elucidate the molecular mechanisms underlying the specific voltage-sensing properties of VGCCs.
- To analyze the structural and kinetic differences between resting and activated states of voltage-sensing domains (VSDs).
Main Methods:
- Utilized structure modeling, mutagenesis, and electrophysiology.
- Analyzed free energy and transition kinetics of VSDs from the CaV1.1 calcium channel.
- Investigated ion-pair formation in the outer gating charges of VSDs.
Main Results:
- Both VSDs followed the sliding helix model but differed significantly in outer gating charge ion-pair formation.
- Stabilizing the activated state increased voltage dependence, while stabilizing resting states slowed kinetics.
- Demonstrated that specific ion-pair formations in VSDs dictate distinct gating properties.
Conclusions:
- Proposed a mechanistic model for how ion-pair formation in VSDs confers specific gating characteristics to VGCCs.
- Highlighted the role of VSDs in realizing the diverse functional properties of voltage-gated cation channels.
Related Concept Videos
01:26Voltage-gated Ion Channels
9.4K
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...
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...
9.4K
01:19The Role of Ion Channels in Neuronal Computation
3.4K
A postsynaptic neuron usually receives numerous impulses from several other presynaptic neurons. The axon hillock of the postsynaptic neuron integrates all these signals and determines the likelihood of firing an action potential.
Sometimes a single EPSP is strong enough to induce an action potential in the postsynaptic neuron. However, multiple presynaptic inputs must often create EPSPs around the same time for the postsynaptic neuron to be sufficiently depolarized to fire an action potential....
Sometimes a single EPSP is strong enough to induce an action potential in the postsynaptic neuron. However, multiple presynaptic inputs must often create EPSPs around the same time for the postsynaptic neuron to be sufficiently depolarized to fire an action potential....
3.4K
01:30Ligand-Gated Ion Channel Receptor: Gating Mechanism
3.2K
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...
3.2K
01:19Ligand-gated Ion Channels
13.4K
Ligand-gated ion channels are transmembrane proteins with a channel for ions to pass through and a binding site for a ligand. The channel opens only when a ligand attaches to the binding site.
Three Subfamilies of Ligand-gated Ion Channels
Ligand-gated ion channels fall into three subfamilies. The 'Cys-loop' includes the nicotinic acetylcholine receptors, γ-aminobutyric acid (GABA), glycine, and 5-hydroxytryptamine receptors. The second one is the 'Pore-loop' channels that...
Three Subfamilies of Ligand-gated Ion Channels
Ligand-gated ion channels fall into three subfamilies. The 'Cys-loop' includes the nicotinic acetylcholine receptors, γ-aminobutyric acid (GABA), glycine, and 5-hydroxytryptamine receptors. The second one is the 'Pore-loop' channels that...
13.4K
01:24Non-gated Ion Channels
7.6K
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....
7.6K
01:12Mechanically-gated Ion Channels
7.2K
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...
7.2K